Oral HYCAMTIN Plus Whole Brain Radiation Therapy In Treatment Of Brain Metastases Resulting From Non-Small Lung Cancer

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00390806
• Collaborator: (none)
• Enrollment: 472
• Locations: 88
• Arms: 2
• Duration (Months): 81
• Patients Per Site: 5.4
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The current prognosis for patients with metastatic brain cancer from NSCLC is very poor. The current standard treatment for this disease is radiation therapy to the brain. The goal of the current study is to test whether the combination of orally administered HYCAMTIN capsules and whole brain radiation therapy will prolong the survival time of patients with this potentially serious condition.

Condition or Disease	Intervention/Treatment	Phase
Lung Cancer, Non-Small Cell	Drug: HYCAMTIN, oral capsules; Radiation: Radiation	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 472 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized, Phase III, Open-Label Study of Oral Topotecan Plus Whole-Brain Radiation Therapy (WBRT) Compared With WBRT Alone in Patients With Brain Metastases From Non-Small Cell Lung Cancer
• Study Start Date: Dec 1, 2006
• Actual Primary Completion Date: Jul 1, 2012
• Actual Study Completion Date: Sep 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: topotecan plus radiation topotecan 1.1 mg/m2 followed by whole brain radiation 3 Gy/day for 10 days, followed by optional continuation therapy with topotecan 2.3 mg/m2 for 5 days Q21 days as monotherapy.	Drug: HYCAMTIN, oral capsules; topotecan oral capsules 1.1 mg/m2; Other Names: HYCAMTIN oral capsules ; Radiation: Radiation; Whole brain radiation
Active Comparator: Whole brain radiation Whole brain radiation 3 Gy/day for 10 days	Radiation: Radiation; Whole brain radiation

Outcome Measures

Primary Outcome Measures

1. Overall Survival [From the time of Randomization until the date of death due to any cause (up to 195 weeks)]

   Overall survival is defined as the time from randomization until the date of death due to any cause. The date of last contact was used for those participants who had not died or were lost to follow-up. These participants were classified as having been censored.

Secondary Outcome Measures

1. Six-month Survival [Month 6]

   Six-month survival is defined as the percentage of participants alive at 6 months following randomization. The date of last contact was used for those participants who had not died or were lost to follow-up. These participants were classified as having been censored.

2. Number of Participants With a Complete Response (CR) or a Partial Response (PR) (Central Nervous System [CNS]-Radiologic) [From the time of Randomization until the time of CR or PR (up to 75 weeks)]

   The number of participants achieving either a CR or PR, per World Health Organization (WHO) Criteria, in the CNS was assessed. CR is defined as the complete disappearance of all known measurable (Must be accurately measured in >=1 dimension) and nonmeasurable disease, without clinical, laboratory, or radiological evidence of recurrence for at least 4 weeks. CR may have been defined in participants with measurable and/or non-measurable disease at Screening. PR is defined as at least a 50% decrease in the sum of the products of the greatest length and perpendicular width of all measurable disease with no clear increase in nonmeasurable disease in participants without measurable disease. In both cases, there must have been no appearance of new disease, and no clinical, laboratory, or radiological evidence of disease progression for at least 4 weeks. Assessment of response was performed by the investigator and was based on unconfirmed responses.

3. Time to Response (TTR) (CNS-radiologic) [From the time of Randomization until the first documented evidence of CR or PR (up to 75 weeks)]

   TTR is defined as the time from Randomization until the first documented evidence of CR or PR in the CNS. CR is defined as the complete disappearance of all known measurable (Must be accurately measured in >=1 dimension) and nonmeasurable disease, without clinical, laboratory, or radiological evidence of recurrence for at least 4 weeks. CR may have been defined in participants with measurable and/or non-measurable disease at Screening. PR is defined as at least a 50% decrease in the sum of the products of the greatest length and perpendicular width of all measurable disease with no clear increase in nonmeasurable disease in participants without measurable disease. In both cases, there must have been no appearance of new disease, and no clinical, laboratory, or radiological evidence of disease progression for at least 4 weeks. Assessment of response was performed by the investigator and was based on unconfirmed responses.

4. Time to Progression (TTP) (CNS-radiologic) [From the time of Randomization until the first documented sign of disease progression (up to 75 weeks)]

   TTP is defined as the time from Randomization until the first documented sign of disease progression in the CNS. Progressive disease (PD) is defined as an increase >=25% in any measurable lesion or, in participants with non-measurable disease only, an estimation of an increase >=25%. In both cases, determination of progression included the appearance of any new lesions, or signification worsening of conditions presumed to be related to malignancy. Participants with clinical or laboratory evidence of possible disease progression were to be evaluated radiologically. TTP was analyzed with censoring for extended loss to follow-up to account for two or more missed assessments before a TTP event. The date of the last adequate CNS assessment before extended loss to follow-up was used for censored participants.

5. Time to Progression (TTP) (All Sites of Disease-radiologic) [From the time of Randomization until the first documented sign of disease progression (up to 75 weeks)]

   TTP is defined as the time from Randomization until the first documented sign of disease progression in all sites of disease. Progressive disease (PD) is defined as an increase >=25% in any measurable lesion or, in participants with non-measurable disease only, an estimation of an increase >=25%. In both cases, determination of progression included the appearance of any new lesions, or signification worsening of conditions presumed to be related to malignancy. Participants with clinical or laboratory evidence of possible disease progression were to be evaluated radiologically. TTP was analyzed with censoring for extended loss to follow-up to account for two or more missed assessments before a TTP event. The date of the last adequate CNS assessment before extended loss to follow-up was used for censored participants.

6. Number of Participants Who Ranked Each Individual Indicated Neurological Sign and Symptom as None, Mild, Moderate, or Severe at Months 1 and 3 [Months 1 and 3]

   Neurological signs and symptoms data were derived from a participant-reported diary. The participants were asked to assess the following signs and symptoms on a scale of none, mild, moderate, or severe at Months 1 and 3: headache, problems with balance/coordination (PB/C), leg weakness, arm weakness, loss of feeling/numbness (LofF/N), speech difficulty (SD), confusion, loss of memory (LofM), drowsiness, nausea, vomiting, dizziness, visual problems (VP), seizures, leg/ankle swelling (L/AS), heart burn, difficulty sleeping (DS), tiredness, and appetite/weight gain (A/WG).

7. Number of Participants With the Indicated Investigator Assessment for the Neurological Sign and Symptom of Level of Consciousness at Baseline, Month 1, and Month 3 [Baseline, Month 1, and Month 3]

   The investigator assessed participants for the neurological sign and symptom of level of consciousness and assigned each participant to one of the following categories: normal; somnolence or sedation not interfering with function (not intefering); somnolence or sedation interfering with function, but not activities of daily living (ADLs) (interfering); obtundation or stupor, difficult to arouse, inteferring with ADLs (obtundation or stupor); coma.

8. Number of Participants With the Indicated Investigator Assessment for the Neurological Sign and Symptom of Headache at Baseline, Month 1, and Month 3 [Baseline, Month 1, and Month 3]

   The investigator (per Common Terminology Criteria for Adverse Events [CTCAE], version 3.0) assessed participants for headache and assigned each participant to one of the following categories: absent, Grade (G) 1, G 2, G 3, G 4, and G 5. Grade refers to the severity of the AE. The CTCAE displays G 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: G 1: mild, asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; G 2: moderate, minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental ADL; G 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated, disabling, limiting self care ADL; G 4: life-threatening consequences, urgent intervention indicated; G 5: death related to AE.

9. Number of Participants With the Indicated Investigator Assessment for the Neurological Sign and Symptom of Dizziness/Lightheadedness at Baseline, Month 1, and Month 3 [Baseline, Month 1, and Month 3]

   The investigator (per CTCAE, version 3.0) assessed participants for dizziness/lightheadedness and assigned each participant to one of the following categories: absent, G 1, G 2, G 3, G 4, and G 5. Grade refers to the severity of the AE. The CTCAE displays G 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: G 1: mild, asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; G 2: moderate, minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental ADL; G 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated, disabling, limiting self care ADL; G 4: life-threatening consequences, urgent intervention indicated; G 5: death related to AE.

10. Number of Participants With the Indicated Investigator Assessment for the Neurological Sign and Symptom of Vertigo at Baseline, Month 1, and Month 3 [Baseline, Month 1, and Month 3]

    The investigator (per CTCAE, version 3.0) assessed participants for vertigo and assigned each participant to one of the following categories: absent, G 1, G 2, G 3, G 4, and G 5. Grade refers to the severity of the AE. The CTCAE displays G 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: G 1: mild, asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; G 2: moderate, minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental ADL; G 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated, disabling, limiting self care ADL; G 4: life-threatening consequences, urgent intervention indicated; G 5: death related to AE.

11. Number of Participants With the Indicated Investigator Assessment for the Neurological Sign and Symptom of Nausea/Vomiting at Baseline, Month 1, and Month 3 [Baseline, Month 1, and Month 3]

    The investigator (per CTCAE, version 3.0) assessed participants for nausea/vomiting and assigned each participant to one of the following categories: absent, G 1, G 2, G 3, G 4, and G 5. Grade refers to the severity of the AE. The CTCAE displays G 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: G 1: mild, asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; G 2: moderate, minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental ADL; G 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated, disabling, limiting self care ADL; G 4: life-threatening consequences, urgent intervention indicated; G 5: death related to AE.

12. Number of Participants With the Indicated Investigator Assessment for the Neurological Sign and Symptom of Visual Problem at Baseline, Month 1, and Month 3 [Baseline, Month 1, and Month 3]

    The investigator (per CTCAE, version 3.0) assessed participants for visual problem and assigned each participant to one of the following categories: absent, G 1, G 2, G 3, G 4, and G 5. Grade refers to the severity of the AE. The CTCAE displays G 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: G 1: mild, asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; G 2: moderate, minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental ADL; G 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated, disabling, limiting self care ADL; G 4: life-threatening consequences, urgent intervention indicated; G 5: death related to AE.

13. Number of Participants With the Indicated Investigator Assessment for the Neurological Sign and Symptom of Seizure at Baseline, Month 1, and Month 3 [Baseline, Month 1, and Month 3]

    The investigator (per CTCAE, version 3.0) assessed participants for seizure and assigned each participant to one of the following categories: absent, G 1, G 2, G 3, G 4, and G 5. Grade refers to the severity of the AE. The CTCAE displays G 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: G 1: mild, asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; G 2: moderate, minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental ADL; G 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated, disabling, limiting self care ADL; G 4: life-threatening consequences, urgent intervention indicated; G 5: death related to AE.

14. Number of Participants With the Indicated Investigator Assessment for the Neurological Sign and Symptom of Other Neurological Symptoms at Baseline, Month 1, and Month 3 [Baseline, Month 1, and Month 3]

    The investigator (per CTCAE, version 3.0) assessed participants for other neurological symptoms and assigned each participant to one of the following categories: absent, G 1, G 2, G 3, G 4, and G 5. Grade refers to the severity of the AE. The CTCAE displays G 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: G 1: mild, asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; G 2: moderate, minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental ADL; G 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated, disabling, limiting self care ADL; G 4: life-threatening consequences, urgent intervention indicated; G 5: death related to AE.

15. Number of Participants With the Indicated Investigator Assessment of Cranial Nerves II-XII at Baseline, Month 1, and Month 3 [Baseline, Month 1, and Month 3]

    The investigator assessed participants' status of cranial nerves II-XII and assigned each participant to one of the following categories: normal; present, not interfering with ADLs; present, interfering with ADLs; life threatening, disabling.

16. Number of Participants With the Indicated Investigator Assessment of Language (Dysphasia or Aphasia) at Baseline, Month 1, and Month 3 [Baseline, Month 1, and Month 3]

    The investigator assessed participants' status of language (dysphasia or aphasia) and assigned each participant to one of the following categories: absent; awareness of receptive or expressive aphasia, not impairing ability to communicate (not impaired); receptive or expressive dysphasia, impairing ability to communicate (impaired); inability to communicate (unable).

17. Number of Participants With the Indicated Investigator Assessment of Strength (Right Upper Extremity) at Baseline, Month 1, and Month 3 [Baseline, Month 1, and Month 3]

    The investigator assessed participants' status of strength (right upper extremity) and assigned each participant to one of the following categories: normal; Grade 1, asymptomatic with weakness on physical examination; Grade 2, symptomatic and interfering with function, but not interfering with ADLs; Grade 3, symptomatic and interfering with ADLs; Grade 4: bedridden or disabling.

18. Number of Participants With the Indicated Investigator Assessment of Strength (Left Upper Extremity) at Baseline, Month 1, and Month 3 [Baseline, Month 1, and Month 3]

    The investigator assessed participants' status of strength (left upper extremity) and assigned each participant to one of the following categories: normal; Grade 1, asymptomatic with weakness on physical examination; Grade 2, symptomatic and interfering with function, but not interfering with ADLs; Grade 3, symptomatic and interfering with ADLs; Grade 4: bedridden or disabling.

19. Number of Participants With the Indicated Investigator Assessment of Strength (Right Lower Extremity) at Baseline, Month 1, and Month 3 [Baseline, Month 1, and Month 3]

    The investigator assessed participants' status of strength (right lower extremity) and assigned each participant to one of the following categories: normal; Grade 1, asymptomatic with weakness on physical examination; Grade 2, symptomatic and interfering with function, but not interfering with ADLs; Grade 3, symptomatic and interfering with ADLs; Grade 4: bedridden or disabling.

20. Number of Participants With the Indicated Investigator Assessment of Strength (Left Lower Extremity) at Baseline, Month 1, and Month 3 [Baseline, Month 1, and Month 3]

    The investigator assessed participants' status of strength (left lower extremity) and assigned each participant to one of the following categories: normal; Grade 1, asymptomatic with weakness on physical examination; Grade 2, symptomatic and interfering with function, but not interfering with ADLs; Grade 3, symptomatic and interfering with ADLs; Grade 4: bedridden or disabling.

21. Number of Participants With the Indicated Investigator Assessment of Sensation at Baseline, Month 1, and Month 3 [Baseline, Month 1, and Month 3]

    The investigator assessed participants' status of sensation and assigned each participant to one of the following categories: normal; loss of deep tendon reflexes or paresthesia, but not interfering with function (not interfering with function); objective sensory loss or paresthesia interfering with function, but not interfering with ADLs (interfering with function); sensory loss or paresthesia interfering with ADLs (intefering with ADLs); permanent sensory loss that interferes with function (permanent sensory loss).

22. Number of Participants With the Indicated Investigator Assessment of Ataxia (Right Upper Extremity: Finger to Nose Testing) at Baseline, Month 1, and Month 3 [Baseline, Month 1, and Month 3]

    The investigator assessed participants' status of ataxia (right upper extremity: finger to nose testing) and assigned each participant to one of the following categories: normal; Grade 1, asymptomatic but abnormal on physical examination, and not interfering with function; Grade 2, mild symptoms interfering with function, but not interfering with ADLs; Grade 3, moderate symptoms interfering with ADLs; Grade 4, bedridden or disabling.

23. Number of Participants With the Indicated Investigator Assessment of Ataxia (Left Upper Extremity: Finger to Nose Testing) at Baseline, Month 1, and Month 3 [Baseline, Month 1, and Month 3]

    The investigator assessed participants' status of ataxia (left upper extremity: finger to nose testing) and assigned each participant to one of the following categories: normal; Grade 1, asymptomatic but abnormal on physical examination, and not interfering with function; Grade 2, mild symptoms interfering with function, but not interfering with ADLs; Grade 3, moderate symptoms interfering with ADLs; Grade 4, bedridden or disabling.

24. Number of Participants With the Indicated Investigator Assessment of Ataxia (Gait) at Baseline, Month 1, and Month 3 [Baseline, Month 1, and Month 3]

    The investigator assessed participants' status of ataxia (gait) and assigned each participant to one of the following categories: normal; Grade 1, asymptomatic but abnormal on physical examination, and not interfering with function; Grade 2, mild symptoms interfering with function, but not interfering with ADLs; Grade 3, moderate symptoms interfering with ADLs; Grade 4, bedridden or disabling.

25. Number of Participants With the Indicated Investigator Assessment of Ataxia (Balance) at Baseline, Month 1, and Month 3 [Baseline, Month 1, and Month 3]

    The investigator assessed participants' status of ataxia (balance) and assigned each participant to one of the following categories: normal; Grade 1, asymptomatic but abnormal on physical examination, and not interfering with function; Grade 2, mild symptoms interfering with function, but not interfering with ADLs; Grade 3, moderate symptoms interfering with ADLs; Grade 4, bedridden or disabling.

26. Number of Participants With Any Adverse Event (AE; Both Serious and Non-serious) or Serious Adverse Event (SAE) [From Randomization until the last clinic visit associated with the study, up until 35 days after the start of the last course of treatment (up to 75 weeks)]

    An AE is defined as any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life threatening; requires hospitalization or prolongation of existing hospitalization; results in disability/incapacity; is a congenital anomaly/birth defect. For a list of all SAEs and AEs, see the SAE/AE module of this results summary.

27. Number of Participants With the Indicated Worst-case Change From Baseline in the Indicated Chemistry Parameters With Respect to the Normal Range [From Randomization until the last clinic visit associated with the study, up until 35 days after the start of the last course of treatment (up to 75 weeks)]

    The worst-case change from Baseline in chemistry parameters was measured as decrease to low (DTL), change to normal or no change (CTN/NC), or increase to high (ITH). The worst-case change value could have been measured at any point during the on-therapy period. Participants are counted twice if the participant "Decreased to Low" and "Increased to High" during the on-therapy period.

28. Lesion Assessment and Measurement [From the time of Randomization until the time of CR or PR (up to 75 weeks)]

    Lesions were assessed per WHO criteria. For lesion assessment data, see the outcome measure entitled "Number of participants with a complete response (CR) or a partial response (PR) (central nervous system [CNS]-radiologic)."

29. Brain Symptoms [Baseline, Month 1, and Month 3]

    Brain symptoms were assessed as the number of participants with neurological signs and symptoms. For brain symptom data, see the outcome measures entitled "Number of participants with the indicated investigator assessment for the neurological sign and symptom of X at Baseline, Month 1, and Month 3."

30. Number of Participants Who Died or Progressed [From Randomization until the last clinic visit associated with the study, up until 35 days after the start of the last course of treatment (up to 75 weeks)]

    Disease-related events were measured as the number of participants who died or progressed. Progressive disease (PD) is defined as an increase >=25% in any measurable lesion or, in participants with non-measurable disease only, an estimation of an increase >=25%. In both cases, determination of progression included the appearance of any new lesions, or signification worsening of conditions presumed to be related to malignancy. Participants with clinical or laboratory evidence of possible disease progression were to be evaluated radiologically. Data were analyzed with censoring for extended loss to follow-up to account for two or more missed assessments before an event. The date of the last adequate CNS assessment before extended loss to follow-up was used for censored participants.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion criteria:

• At least one measurable cancerous lesion in the brain from primary non-small cell lung cancer (NSCLC)

• Must have received previous chemotherapy

• Must be 18 years of age of greater

• Must be Easter Cooperative Oncology Group (ECOG) Performance Status 0, 1, 2

• At least 2 weeks must have elapsed since any surgery

• At least 4 weeks must have elapsed since any radiation to a non-CNS site

• Must have adequate bone marrow, renal, and live capacities

• Women must be of non-childbearing potential or practice adequate birth control

• Males must practice adequate methods of birth control

• Must sign written informed consent

Exclusion criteria:

• Previous whole brain radiation therapy

• Prior treatment with topotecan

• Investigational agent within 30 days or 5 half-live

• Concomitant therapy with inhibitors of breast cancer resistance protein (BCRP) or P-glycoprotein such as erlotinib or gefitinib

• Primary or secondary immunodeficiencies

• Gastrointestinal conditions that affect GI absorption or motility

• Uncontrolled emesis

• Brain metastasis at time of initial diagnosis of NSCLC

• History of other malignancy except in situ carcinoma of cervix; nonmelanomatous skin cancer, low grade prostate cancer

• Pregnant or intending to become pregnant or intending to father a baby

• Any severe concurrent medical condition that could affect compliance.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Birmingham	Alabama	United States	35294
2	GSK Investigational Site	Glendale	Arizona	United States	85304
3	GSK Investigational Site	Hot Springs	Arkansas	United States	71913
4	GSK Investigational Site	Anaheim	California	United States	92801
5	GSK Investigational Site	Duarte	California	United States	91010-3000
6	GSK Investigational Site	Pleasant Hill	California	United States	94523
7	GSK Investigational Site	Aurora	Colorado	United States	80012
8	GSK Investigational Site	Lakeland	Florida	United States	33805
9	GSK Investigational Site	Tampa	Florida	United States	33606
10	GSK Investigational Site	Tampa	Florida	United States	33612
11	GSK Investigational Site	Chicago	Illinois	United States	60612
12	GSK Investigational Site	Elk Grove Village	Illinois	United States	60007
13	GSK Investigational Site	Galesburg	Illinois	United States	61401
14	GSK Investigational Site	Park Ridge	Illinois	United States	60068
15	GSK Investigational Site	Rockford	Illinois	United States	61108
16	GSK Investigational Site	Skokie	Illinois	United States	60077
17	GSK Investigational Site	Indianapolis	Indiana	United States	46227
18	GSK Investigational Site	Westwood	Kansas	United States	66205
19	GSK Investigational Site	Paducah	Kentucky	United States	42003
20	GSK Investigational Site	Metairie	Louisiana	United States	70006
21	GSK Investigational Site	Minneapolis	Minnesota	United States	55455
22	GSK Investigational Site	Jackson	Mississippi	United States	39216
23	GSK Investigational Site	Columbia	Missouri	United States	65201
24	GSK Investigational Site	Kansas City	Missouri	United States	64154
25	GSK Investigational Site	Lincoln	Nebraska	United States	68510
26	GSK Investigational Site	Las Vegas	Nevada	United States	89106
27	GSK Investigational Site	Las Vegas	Nevada	United States	89135
28	GSK Investigational Site	Albuquerque	New Mexico	United States	87109
29	GSK Investigational Site	Albany	New York	United States	12206
30	GSK Investigational Site	Bronx	New York	United States	10467
31	GSK Investigational Site	Buffalo	New York	United States	14215-1199
32	GSK Investigational Site	Buffalo	New York	United States	14215
33	GSK Investigational Site	Columbus	Ohio	United States	43235
34	GSK Investigational Site	Eugene	Oregon	United States	97401-8122
35	GSK Investigational Site	Charleston	South Carolina	United States	29403
36	GSK Investigational Site	Bedford	Texas	United States	76022
37	GSK Investigational Site	Corpus Christi	Texas	United States	78412
38	GSK Investigational Site	Dallas	Texas	United States	75320-2510
39	GSK Investigational Site	Duncanville	Texas	United States	75137
40	GSK Investigational Site	Fort Worth	Texas	United States	76104
41	GSK Investigational Site	Lubbock	Texas	United States	79415
42	GSK Investigational Site	Sherman	Texas	United States	75090
43	GSK Investigational Site	Sugarland	Texas	United States	77479
44	GSK Investigational Site	Everett	Washington	United States	98201
45	GSK Investigational Site	Vancouver	Washington	United States	98684
46	GSK Investigational Site	Madison	Wisconsin	United States	53792
47	GSK Investigational Site	Moncton	New Brunswick	Canada	E1C 8X3
48	GSK Investigational Site	Hamilton	Ontario	Canada	L8V 5C2
49	GSK Investigational Site	Kingston	Ontario	Canada	K7L 5P9
50	GSK Investigational Site	London	Ontario	Canada	N6A 4L6
51	GSK Investigational Site	Toronto	Ontario	Canada	M5G 2M9
52	GSK Investigational Site	Greenfield Park	Quebec	Canada	J4V 2H1
53	GSK Investigational Site	Montreal	Quebec	Canada	H1T 2M4
54	GSK Investigational Site	Montreal	Quebec	Canada	H2L 4M1
55	GSK Investigational Site	Sherbrooke	Quebec	Canada	J1H 5N4
56	GSK Investigational Site	Quebec		Canada	G1R 2J6
57	GSK Investigational Site	Budapest		Hungary	1529
58	GSK Investigational Site	Csorna		Hungary	9300
59	GSK Investigational Site	Gyula		Hungary	5703
60	GSK Investigational Site	Győr		Hungary	9024
61	GSK Investigational Site	Miskolc		Hungary	3529
62	GSK Investigational Site	Mátraháza		Hungary	3233
63	GSK Investigational Site	Nyíregyháza		Hungary	4400
64	GSK Investigational Site	Pécs		Hungary	7623
65	GSK Investigational Site	Szombathely		Hungary	9700
66	GSK Investigational Site	Székesfehérvár		Hungary	8000
67	GSK Investigational Site	Törökbálint		Hungary	2045
68	GSK Investigational Site	Zalaegerszeg-Pozva		Hungary	8900
69	GSK Investigational Site	Bialystok		Poland	15-540
70	GSK Investigational Site	Bydgoszcz		Poland	85-769
71	GSK Investigational Site	Gdansk		Poland	80-211
72	GSK Investigational Site	Krakow		Poland	31-115
73	GSK Investigational Site	Olsztyn		Poland	10-226
74	GSK Investigational Site	Olsztyn		Poland	10-357
75	GSK Investigational Site	Poznan		Poland	60-569
76	GSK Investigational Site	Kazan		Russian Federation	420111
77	GSK Investigational Site	Moscow		Russian Federation	105229
78	GSK Investigational Site	Moscow		Russian Federation	115 478
79	GSK Investigational Site	Moscow		Russian Federation	128128
80	GSK Investigational Site	Moscow		Russian Federation	129 128
81	GSK Investigational Site	Obninsk		Russian Federation	249036
82	GSK Investigational Site	Orenburg		Russian Federation	460021
83	GSK Investigational Site	St-Petersburg		Russian Federation	197758
84	GSK Investigational Site	St. Petersburg		Russian Federation	197022
85	GSK Investigational Site	Voronezh		Russian Federation	394062
86	GSK Investigational Site	Banska Bystrica		Slovakia	975 17
87	GSK Investigational Site	Bratislava		Slovakia	826 06
88	GSK Investigational Site	Nitra		Slovakia	949 01

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT00390806
• Other Study ID Numbers: HYT105962
• First Posted: Oct 20, 2006
• Last Update Posted: Jan 20, 2014
• Last Verified: Dec 1, 2013

• Keywords provided by GlaxoSmithKline: Brain metastases from Non-Small Cell Lung Cancer; Brain metastases brain tumor lung cancer oral chemotherapy HYCAMTIN topotecan NSCLC WBRT whole brain radiation
• Additional relevant MeSH terms: Lung Neoplasms; Neoplasm Metastasis; Brain Neoplasms; Carcinoma, Non-Small-Cell Lung; Topotecan

Study Results

Participant Flow

Arm/Group Title	Chemoradiation: Topotecan Plus WBRT	Radiation: WBRT Alone
Arm/Group Description	Participants received topotecan 1.1 milligrams per meters squared per day (mg/m2/day), orally followed approximately 2 hours later by whole-brain radiation therapy (WBRT) 3 Gray (Gy)/day to midline over the course of 10 days. After a 2-week washout period, participants completing chemoradiation and willing to participate in the Continuation Phase of the study received oral topotecan 2.3 mg/m2/day for 5 days, every 21 days, as monotherapy provided the baseline hematologic requirements were met. Monotherapy continued until disease progression or discontinuation. Chemoradiation participants choosing not to participate in the Continuation Phase may have received other chemotherapies or best supportive care, as determined by the investigator.	Participants received WBRT 3 Gy/day for 10 days. Participants may have received other chemotherapies or best supportive care, as determined by the investigator.
Period Title: Overall Study
STARTED	236	236
Ongoing	4	2
COMPLETED	206	204
NOT COMPLETED	30	32

Baseline Characteristics

Arm/Group Title	Chemoradiation: Topotecan Plus WBRT	Radiation: WBRT Alone	Total
Arm/Group Description	Participants received topotecan 1.1 milligrams per meters squared per day (mg/m2/day), orally followed approximately 2 hours later by whole-brain radiation therapy (WBRT) 3 Gray (Gy)/day to midline over the course of 10 days. After a 2-week washout period, participants completing chemoradiation and willing to participate in the Continuation Phase of the study received oral topotecan 2.3 mg/m2/day for 5 days, every 21 days, as monotherapy provided the baseline hematologic requirements were met. Monotherapy continued until disease progression or discontinuation. Chemoradiation participants choosing not to participate in the Continuation Phase may have received other chemotherapies or best supportive care, as determined by the investigator.	Participants received WBRT 3 Gy/day for 10 days. Participants may have received other chemotherapies or best supportive care, as determined by the investigator.	Total of all reporting groups
Overall Participants	236	236	472
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	59.4 (8.56)	57.8 (8.65)	58.6 (8.63)
Sex: Female, Male (Count of Participants)
Female	84 35.6%	78 33.1%	162 34.3%
Male	152 64.4%	158 66.9%	310 65.7%
Race/Ethnicity, Customized (participants) [Number]
African American/African Heritage (Her.)	3 1.3%	1 0.4%	4 0.8%
Central/South Asian Heritage	1 0.4%	0 0%	1 0.2%
Japanese/East Asian Heritage/South East Asian Her.	0 0%	3 1.3%	3 0.6%
Native Hawaiian or other Pacific Islander	1 0.4%	0 0%	1 0.2%
White	230 97.5%	232 98.3%	462 97.9%
Asian & White	1 0.4%	0 0%	1 0.2%

Outcome Measures

1. Primary Outcome

Title	Overall Survival
Description	Overall survival is defined as the time from randomization until the date of death due to any cause. The date of last contact was used for those participants who had not died or were lost to follow-up. These participants were classified as having been censored.
Time Frame	From the time of Randomization until the date of death due to any cause (up to 195 weeks)

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) Population: all randomized participants. Participants were analyzed by the treatment to which they were randomized, even if this differed from the treatment they actually received.

Arm/Group Title	Chemoradiation: Topotecan Plus WBRT	Radiation: WBRT Alone
Arm/Group Description	Participants received topotecan 1.1 milligrams per meters squared per day (mg/m2/day), orally followed approximately 2 hours later by whole-brain radiation therapy (WBRT) 3 Gray (Gy)/day to midline over the course of 10 days. After a 2-week washout period, participants completing chemoradiation and willing to participate in the Continuation Phase of the study received oral topotecan 2.3 mg/m2/day for 5 days, every 21 days, as monotherapy provided the baseline hematologic requirements were met. Monotherapy continued until disease progression or discontinuation. Chemoradiation participants choosing not to participate in the Continuation Phase may have received other chemotherapies or best supportive care, as determined by the investigator.	Participants received WBRT 3 Gy/day for 10 days. Participants may have received other chemotherapies or best supportive care, as determined by the investigator.
Measure Participants	236	236
Median (95% Confidence Interval) [months]	4.0	3.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Chemoradiation: Topotecan Plus WBRT, Radiation: WBRT Alone
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1862
	Comments	p-value from a stratified log-rank test is adjusted for Recursive Partitioning Analysis (RPA) class and the number of brain lesions at Screening.
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.88
	Confidence Interval	(2-Sided) 95%; 0.73 to 1.07
	Parameter Dispersion	Type: Value:
	Estimation Comments	The hazard ratio is estimated using a Pike estimator. The hazard ratio from a stratified log-rank test is adjusted for RPA class and the number of brain lesions at Screening.

2. Secondary Outcome

Title	Six-month Survival
Description	Six-month survival is defined as the percentage of participants alive at 6 months following randomization. The date of last contact was used for those participants who had not died or were lost to follow-up. These participants were classified as having been censored.
Time Frame	Month 6

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Chemoradiation: Topotecan Plus WBRT	Radiation: WBRT Alone
Arm/Group Description	Participants received topotecan 1.1 milligrams per meters squared per day (mg/m2/day), orally followed approximately 2 hours later by whole-brain radiation therapy (WBRT) 3 Gray (Gy)/day to midline over the course of 10 days. After a 2-week washout period, participants completing chemoradiation and willing to participate in the Continuation Phase of the study received oral topotecan 2.3 mg/m2/day for 5 days, every 21 days, as monotherapy provided the baseline hematologic requirements were met. Monotherapy continued until disease progression or discontinuation. Chemoradiation participants choosing not to participate in the Continuation Phase may have received other chemotherapies or best supportive care, as determined by the investigator.	Participants received WBRT 3 Gy/day for 10 days. Participants may have received other chemotherapies or best supportive care, as determined by the investigator.
Measure Participants	236	236
Number [percentage of participants]	36 15.3%	28 11.9%

3. Secondary Outcome

Title	Number of Participants With a Complete Response (CR) or a Partial Response (PR) (Central Nervous System [CNS]-Radiologic)
Description	The number of participants achieving either a CR or PR, per World Health Organization (WHO) Criteria, in the CNS was assessed. CR is defined as the complete disappearance of all known measurable (Must be accurately measured in >=1 dimension) and nonmeasurable disease, without clinical, laboratory, or radiological evidence of recurrence for at least 4 weeks. CR may have been defined in participants with measurable and/or non-measurable disease at Screening. PR is defined as at least a 50% decrease in the sum of the products of the greatest length and perpendicular width of all measurable disease with no clear increase in nonmeasurable disease in participants without measurable disease. In both cases, there must have been no appearance of new disease, and no clinical, laboratory, or radiological evidence of disease progression for at least 4 weeks. Assessment of response was performed by the investigator and was based on unconfirmed responses.
Time Frame	From the time of Randomization until the time of CR or PR (up to 75 weeks)

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Chemoradiation: Topotecan Plus WBRT	Radiation: WBRT Alone
Arm/Group Description	Participants received topotecan 1.1 milligrams per meters squared per day (mg/m2/day), orally followed approximately 2 hours later by whole-brain radiation therapy (WBRT) 3 Gray (Gy)/day to midline over the course of 10 days. After a 2-week washout period, participants completing chemoradiation and willing to participate in the Continuation Phase of the study received oral topotecan 2.3 mg/m2/day for 5 days, every 21 days, as monotherapy provided the baseline hematologic requirements were met. Monotherapy continued until disease progression or discontinuation. Chemoradiation participants choosing not to participate in the Continuation Phase may have received other chemotherapies or best supportive care, as determined by the investigator.	Participants received WBRT 3 Gy/day for 10 days. Participants may have received other chemotherapies or best supportive care, as determined by the investigator.
Measure Participants	236	236
Complete response	23 9.7%	11 4.7%
Partial response	63 26.7%	61 25.8%

4. Secondary Outcome

Title	Time to Response (TTR) (CNS-radiologic)
Description	TTR is defined as the time from Randomization until the first documented evidence of CR or PR in the CNS. CR is defined as the complete disappearance of all known measurable (Must be accurately measured in >=1 dimension) and nonmeasurable disease, without clinical, laboratory, or radiological evidence of recurrence for at least 4 weeks. CR may have been defined in participants with measurable and/or non-measurable disease at Screening. PR is defined as at least a 50% decrease in the sum of the products of the greatest length and perpendicular width of all measurable disease with no clear increase in nonmeasurable disease in participants without measurable disease. In both cases, there must have been no appearance of new disease, and no clinical, laboratory, or radiological evidence of disease progression for at least 4 weeks. Assessment of response was performed by the investigator and was based on unconfirmed responses.
Time Frame	From the time of Randomization until the first documented evidence of CR or PR (up to 75 weeks)

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants with a CR, PR, or a missing response were assessed. TTR was analyzed with censoring for extended loss to follow-up to account for two or more missed response assessments before a TTR event. The date of the last adequate CNS assessment before extended loss to follow-up was used for censored participants.

Arm/Group Title	Chemoradiation: Topotecan Plus WBRT	Radiation: WBRT Alone
Arm/Group Description	Participants received topotecan 1.1 milligrams per meters squared per day (mg/m2/day), orally followed approximately 2 hours later by whole-brain radiation therapy (WBRT) 3 Gray (Gy)/day to midline over the course of 10 days. After a 2-week washout period, participants completing chemoradiation and willing to participate in the Continuation Phase of the study received oral topotecan 2.3 mg/m2/day for 5 days, every 21 days, as monotherapy provided the baseline hematologic requirements were met. Monotherapy continued until disease progression or discontinuation. Chemoradiation participants choosing not to participate in the Continuation Phase may have received other chemotherapies or best supportive care, as determined by the investigator.	Participants received WBRT 3 Gy/day for 10 days. Participants may have received other chemotherapies or best supportive care, as determined by the investigator.
Measure Participants	173	170
Median (95% Confidence Interval) [weeks]	8.0	8.1

5. Secondary Outcome

Title	Time to Progression (TTP) (CNS-radiologic)
Description	TTP is defined as the time from Randomization until the first documented sign of disease progression in the CNS. Progressive disease (PD) is defined as an increase >=25% in any measurable lesion or, in participants with non-measurable disease only, an estimation of an increase >=25%. In both cases, determination of progression included the appearance of any new lesions, or signification worsening of conditions presumed to be related to malignancy. Participants with clinical or laboratory evidence of possible disease progression were to be evaluated radiologically. TTP was analyzed with censoring for extended loss to follow-up to account for two or more missed assessments before a TTP event. The date of the last adequate CNS assessment before extended loss to follow-up was used for censored participants.
Time Frame	From the time of Randomization until the first documented sign of disease progression (up to 75 weeks)

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Chemoradiation: Topotecan Plus WBRT	Radiation: WBRT Alone
Arm/Group Description	Participants received topotecan 1.1 milligrams per meters squared per day (mg/m2/day), orally followed approximately 2 hours later by whole-brain radiation therapy (WBRT) 3 Gray (Gy)/day to midline over the course of 10 days. After a 2-week washout period, participants completing chemoradiation and willing to participate in the Continuation Phase of the study received oral topotecan 2.3 mg/m2/day for 5 days, every 21 days, as monotherapy provided the baseline hematologic requirements were met. Monotherapy continued until disease progression or discontinuation. Chemoradiation participants choosing not to participate in the Continuation Phase may have received other chemotherapies or best supportive care, as determined by the investigator.	Participants received WBRT 3 Gy/day for 10 days. Participants may have received other chemotherapies or best supportive care, as determined by the investigator.
Measure Participants	236	236
Median (95% Confidence Interval) [weeks]	9.7	9.7

6. Secondary Outcome

Title	Time to Progression (TTP) (All Sites of Disease-radiologic)
Description	TTP is defined as the time from Randomization until the first documented sign of disease progression in all sites of disease. Progressive disease (PD) is defined as an increase >=25% in any measurable lesion or, in participants with non-measurable disease only, an estimation of an increase >=25%. In both cases, determination of progression included the appearance of any new lesions, or signification worsening of conditions presumed to be related to malignancy. Participants with clinical or laboratory evidence of possible disease progression were to be evaluated radiologically. TTP was analyzed with censoring for extended loss to follow-up to account for two or more missed assessments before a TTP event. The date of the last adequate CNS assessment before extended loss to follow-up was used for censored participants.
Time Frame	From the time of Randomization until the first documented sign of disease progression (up to 75 weeks)

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Chemoradiation: Topotecan Plus WBRT	Radiation: WBRT Alone
Arm/Group Description	Participants received topotecan 1.1 milligrams per meters squared per day (mg/m2/day), orally followed approximately 2 hours later by whole-brain radiation therapy (WBRT) 3 Gray (Gy)/day to midline over the course of 10 days. After a 2-week washout period, participants completing chemoradiation and willing to participate in the Continuation Phase of the study received oral topotecan 2.3 mg/m2/day for 5 days, every 21 days, as monotherapy provided the baseline hematologic requirements were met. Monotherapy continued until disease progression or discontinuation. Chemoradiation participants choosing not to participate in the Continuation Phase may have received other chemotherapies or best supportive care, as determined by the investigator.	Participants received WBRT 3 Gy/day for 10 days. Participants may have received other chemotherapies or best supportive care, as determined by the investigator.
Measure Participants	236	236
Median (95% Confidence Interval) [weeks]	8.0	7.7

7. Secondary Outcome

Title	Number of Participants Who Ranked Each Individual Indicated Neurological Sign and Symptom as None, Mild, Moderate, or Severe at Months 1 and 3
Description	Neurological signs and symptoms data were derived from a participant-reported diary. The participants were asked to assess the following signs and symptoms on a scale of none, mild, moderate, or severe at Months 1 and 3: headache, problems with balance/coordination (PB/C), leg weakness, arm weakness, loss of feeling/numbness (LofF/N), speech difficulty (SD), confusion, loss of memory (LofM), drowsiness, nausea, vomiting, dizziness, visual problems (VP), seizures, leg/ankle swelling (L/AS), heart burn, difficulty sleeping (DS), tiredness, and appetite/weight gain (A/WG).
Time Frame	Months 1 and 3

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants who were assessed for the indicated sign and symptom at the indicated time point were analyzed.

Arm/Group Title	Chemoradiation: Topotecan Plus WBRT	Radiation: WBRT Alone
Arm/Group Description	Participants received topotecan 1.1 milligrams per meters squared per day (mg/m2/day), orally followed approximately 2 hours later by whole-brain radiation therapy (WBRT) 3 Gray (Gy)/day to midline over the course of 10 days. After a 2-week washout period, participants completing chemoradiation and willing to participate in the Continuation Phase of the study received oral topotecan 2.3 mg/m2/day for 5 days, every 21 days, as monotherapy provided the baseline hematologic requirements were met. Monotherapy continued until disease progression or discontinuation. Chemoradiation participants choosing not to participate in the Continuation Phase may have received other chemotherapies or best supportive care, as determined by the investigator.	Participants received WBRT 3 Gy/day for 10 days. Participants may have received other chemotherapies or best supportive care, as determined by the investigator.
Measure Participants	179	189
Headache, Month 1, none, n=179, 189	93 39.4%	106 44.9%
Headache, Month 1, mild, n=179, 189	71 30.1%	68 28.8%
Headache, Month 1, moderate, 179, 189	11 4.7%	13 5.5%
Headache, Month 1, severe, 179, 189	4 1.7%	2 0.8%
Headache, Month 3, none, n=109, 111	69 29.2%	53 22.5%
Headache, Month 3, mild, n=109, 111	33 14%	41 17.4%
Headache, Month 3, moderate, n=109, 111	5 2.1%	14 5.9%
Headache, Month 3, severe, n=109, 111	2 0.8%	3 1.3%
PB/C, Month 1, none, n=179, 188	84 35.6%	79 33.5%
PB/C, Month 1, mild, n=179, 188	66 28%	71 30.1%
PB/C, Month 1, moderate, n=179, 188	22 9.3%	30 12.7%
PB/C, Month 1, severe, n=179, 188	7 3%	8 3.4%
PB/C, Month 3, none, n=109, 111	69 29.2%	46 19.5%
PB/C, Month 3, mild, n=109, 111	28 11.9%	36 15.3%
PB/C, Month 3, moderate, n=109, 111	10 4.2%	18 7.6%
PB/C, Month 3, severe, n=109, 111	2 0.8%	11 4.7%
Leg weakness, Month 1, none, n=179, 188	47 19.9%	59 25%
Leg weakness, Month 1, mild, n=179, 188	73 30.9%	72 30.5%
Leg weakness, Month 1, moderate, n=179, 188	41 17.4%	41 17.4%
Leg weakness, Month 1, severe, n=179, 188	18 7.6%	16 6.8%
Leg weakness, Month 3, none, n=109, 111	28 11.9%	34 14.4%
Leg weakness, Month 3, mild, n=109, 111	51 21.6%	37 15.7%
Leg weakness, Month 3, moderate, n=109, 111	20 8.5%	19 8.1%
Leg weakness, Month 3, severe, n=109, 111	10 4.2%	21 8.9%
Arm weakness, Month 1, none, n=179, 188	96 40.7%	97 41.1%
Arm weakness, Month 1, mild, n=179, 188	55 23.3%	60 25.4%
Arm weakness, Month 1, moderate, n=179, 188	23 9.7%	18 7.6%
Arm weakness, Month 1, severe, n=179, 188	5 2.1%	13 5.5%
Arm weakness, Month 3, none, n=109, 111	60 25.4%	53 22.5%
Arm weakness, Month 3, mild, n=109, 111	39 16.5%	34 14.4%
Arm weakness, Month 3, molderate, n=109, 111	8 3.4%	16 6.8%
Arm weakness, Month 3, severe, n=109, 111	2 0.8%	8 3.4%
LofF/N, Month 1, none, n=179, 188	101 42.8%	11 4.7%
LofF/N, Month 1, mild, n=179, 188	53 22.5%	43 18.2%
LofF/N, Month 1, moderate, n=179, 188	17 7.2%	25 10.6%
LofF/N, Month 1, severe, n=179, 188	8 3.4%	9 3.8%
LofF/N, Month 3, none, n=109, 111	73 30.9%	66 28%
LofF/N, Month 3, mild, n=109, 111	28 11.9%	27 11.4%
LofF/N, Month 3, moderate, n=109, 111	3 1.3%	11 4.7%
LofF/N, Month 3, severe, n=109, 111	5 2.1%	7 3%
SD, Month 1, none, n=179, 188	151 64%	137 58.1%
SD, Month 1, mild, n=179, 188	16 6.8%	40 16.9%
SD, Month 1, moderate, n=179, 188	9 3.8%	9 3.8%
SD, Month 1, severe, n=179, 188	3 1.3%	2 0.8%
SD, Month 3, none, n=109, 110	94 39.8%	78 33.1%
SD, Month 3, mild, n=109, 110	11 4.7%	22 9.3%
SD, Month 3, moderate, n=109, 110	2 0.8%	8 3.4%
SD, Month 3, severe, n=109, 110	2 0.8%	2 0.8%
Confusion, Month 1, none, n=179, 188	150 63.6%	148 62.7%
Confusion, Month 1, mild, n=179, 188	20 8.5%	32 13.6%
Confusion, Month 1, moderate, n=179, 188	6 2.5%	7 3%
Confusion, Month 1, severe, n=179, 188	3 1.3%	1 0.4%
Confusion, Month 3, none, n=109, 110	99 41.9%	71 30.1%
Confusion, Month 3, mild, n=109, 110	7 3%	29 12.3%
Confusion, Month 3, moderate, n=109, 110	2 0.8%	9 3.8%
Confusion, Month 3, severe, n=109, 110	1 0.4%	1 0.4%
LofM, Month 1, none, n=179, 188	149 63.1%	141 59.7%
LofM, Month 1, mild, n=179, 188	20 8.5%	41 17.4%
LofM, Month 1, moderate, n=179, 188	8 3.4%	5 2.1%
LofM, Month 1, severe, n=179, 188	2 0.8%	1 0.4%
LofM, Month 3, none, n=109, 110	93 39.4%	78 33.1%
LofM, Month 3, mild, n=109, 110	14 5.9%	25 10.6%
LofM, Month 3, moderate, n=109, 110	1 0.4%	6 2.5%
LofM, Month 3, severe, n=109, 110	1 0.4%	1 0.4%
Drowsiness, Month 1, none, n=179, 188	90 38.1%	96 40.7%
Drowsiness, Month 1, mild, n=179, 188	55 23.3%	59 25%
Drowsiness, Month 1, moderate, n=179, 188	25 10.6%	26 11%
Drowsiness, Month 1, severe, n=179, 188	9 3.8%	7 3%
Drowsiness, Month 3, none, n=109, 111	50 21.2%	44 18.6%
Drowsiness, Month 3, mild, n=109, 111	42 17.8%	40 16.9%
Drowsiness, Month 3, moderate, n=109, 111	15 6.4%	15 6.4%
Drowsiness, Month 3, severe, n=109, 111	2 0.8%	12 5.1%
Nausea, Month 1, none, n=179, 188	125 53%	142 60.2%
Nausea, Month 1, mild, n=179, 188	38 16.1%	36 15.3%
Nausea, Month 1, moderate, n=179, 188	12 5.1%	10 4.2%
Nausea, Month 1, severe, n=179, 188	4 1.7%	0 0%
Nausea, Month 3, none, n=109, 111	70 29.7%	73 30.9%
Nausea, Month 3, mild, n=109, 111	31 13.1%	29 12.3%
Nausea, Month 3, moderate, n=109, 111	7 3%	6 2.5%
Nausea, Month 3, severe, n=109, 111	1 0.4%	3 1.3%
Vomiting, Month 1, none, n=179, 188	153 64.8%	164 69.5%
Vomiting, Month 1, mild, n=179, 188	20 8.5%	19 8.1%
Vomiting, Month 1, moderate, n=179, 188	4 1.7%	4 1.7%
Vomiting, Month 1, severe, n=179, 188	2 0.8%	1 0.4%
Vomiting, Month 3, none, n=109, 111	89 37.7%	91 38.6%
Vomiting, Month 3, mild, n=109, 111	15 6.4%	15 6.4%
Vomiting, Month 3, moderate, n=109, 111	4 1.7%	3 1.3%
Vomiting, Month 3, severe=109, 111	1 0.4%	2 0.8%
Dizziness, Month 1, none, n=179, 188	96 40.7%	94 39.8%
Dizziness, Month 1, mild, n=179, 188	58 24.6%	70 29.7%
Dizziness, Month 1, moderate, n=179, 188	22 9.3%	21 8.9%
Dizziness, Month 1, severe, n=179, 188	3 1.3%	3 1.3%
Dizziness, Month 3, none, n=109, 111	64 27.1%	54 22.9%
Dizziness, Month 3, mild, n=109, 111	35 14.8%	36 15.3%
Dizziness, Month 3, moderate, n=109, 111	7 3%	14 5.9%
Dizziness, Month 3, severe, n=109, 111	3 1.3%	7 3%
VP, Month 1, none, n=179, 188	103 43.6%	117 49.6%
VP, Month 1, mild, n=179, 188	54 22.9%	53 22.5%
VP, Month 1, moderate, n=179, 188	17 7.2%	16 6.8%
VP, Month 1, severe, n=179, 188	5 2.1%	2 0.8%
VP, Month 3, none, n=109, 111	72 30.5%	69 29.2%
VP, Month 3, mild, n=109, 111	29 12.3%	28 11.9%
VP, Month 3, moderate, n=109, 111	7 3%	10 4.2%
VP, Month 3, severe, n=109, 111	1 0.4%	4 1.7%
Seizures, Month 1, none, n=179, 188	173 73.3%	179 75.8%
Seizures, Month 1, mild, n=179, 188	5 2.1%	7 3%
Seizures, Month 1, moderate, n=179, 188	1 0.4%	2 0.8%
Seizures, Month 1, severe, n=179, 188	0 0%	0 0%
Seizures, Month 3, none, n=109, 110	108 45.8%	102 43.2%
Seizures, Month 3, mild, n=109, 110	0 0%	4 1.7%
Seizures, Month 3, moderate, n=109, 110	1 0.4%	3 1.3%
Seizures, Month 3, severe, n=109, 110	0 0%	1 0.4%
L/AS, Month 1, none, n=179, 188	141 59.7%	138 58.5%
L/AS, Month 1, mild, n=179, 188	21 8.9%	29 12.3%
L/AS, Month 1, moderate, n=179, 188	12 5.1%	15 6.4%
L/AS, Month 1, severe, n=179, 188	5 2.1%	6 2.5%
L/AS, Month 3, none, n=109, 111	86 36.4%	85 36%
L/AS, Month 3, mild, n=109, 111	19 8.1%	19 8.1%
L/AS, Month 3, moderate, n=109, 111	3 1.3%	6 2.5%
L/AS, Month 3, severe, n=109, 111	1 0.4%	1 0.4%
Heartburn, Month 1, none, n=179, 188	142 60.2%	151 64%
Heartburn, Month 1, mild, n=179, 188	26 11%	27 11.4%
Heartburn, Month 1, moderate, n=179, 188	9 3.8%	9 3.8%
Heartburn, Month 1, severe, n=179, 188	2 0.8%	1 0.4%
Heartburn, Month 3, none, n=109, 111	87 36.9%	86 36.4%
Heartburn, Month 3, mild, n=109, 111	16 6.8%	18 7.6%
Heartburn, Month 3, moderate, n=109, 111	4 1.7%	6 2.5%
Heartburn, Month 3, severe, n=109, 111	2 0.8%	1 0.4%
DS, Month 1, none, n=179, 188	112 47.5%	109 46.2%
DS, Month 1, mild, n=179, 188	41 17.4%	48 20.3%
DS, Month 1, moderate, n=179, 188	15 6.4%	24 10.2%
DS, Month 1, severe, n=179, 188	11 4.7%	7 3%
DS, Month 3, none, n=109, 110	78 33.1%	71 30.1%
DS, Month 3, mild, n=109, 110	20 8.5%	23 9.7%
DS, Month 3, moderate, n=109, 110	8 3.4%	12 5.1%
DS, Month 3, severe, n=109, 110	3 1.3%	4 1.7%
Tiredness, Month 1, none, n=179, 188	42 17.8%	42 17.8%
Tiredness, Month 1, mild, n=179, 188	75 31.8%	85 36%
Tiredness, Month 1, moderate, n=179, 188	46 19.5%	44 18.6%
Tiredness, Month 1, severe, n=179, 188	16 6.8%	17 7.2%
Tiredness, Month 3, none, n=109, 111	28 11.9%	21 8.9%
Tiredness, Month 3, mild, n=109, 111	52 22%	42 17.8%
Tiredness, Month 3, moderate, n=109, 111	19 8.1%	32 13.6%
Tiredness, Month 3, severe, n=109, 111	10 4.2%	16 6.8%
A/WG, Month 1, none, n=179, 188	107 45.3%	113 47.9%
A/WG, Month 1, mild, n=179, 188	42 17.8%	41 17.4%
A/WG, Month 1, moderate, n=179, 188	19 8.1%	29 12.3%
A/WG, Month 1, severe, n=179, 188	11 4.7%	5 2.1%
A/WG, Month 3, none, n=108, 111	71 30.1%	73 30.9%
A/WG, Month 3, mild, n=108, 111	27 11.4%	23 9.7%
A/WG, Month 3, moderate, n=108, 111	4 1.7%	11 4.7%
A/WG, Month 3, severe, n=108, 111	6 2.5%	4 1.7%

8. Secondary Outcome

Title	Number of Participants With the Indicated Investigator Assessment for the Neurological Sign and Symptom of Level of Consciousness at Baseline, Month 1, and Month 3
Description	The investigator assessed participants for the neurological sign and symptom of level of consciousness and assigned each participant to one of the following categories: normal; somnolence or sedation not interfering with function (not intefering); somnolence or sedation interfering with function, but not activities of daily living (ADLs) (interfering); obtundation or stupor, difficult to arouse, inteferring with ADLs (obtundation or stupor); coma.
Time Frame	Baseline, Month 1, and Month 3

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants who were assessed at the indicated time point were analyzed. If no data are presented for a particular status at a particular time point, then no participants had that status at that time point.

Arm/Group Title	Chemoradiation: Topotecan Plus WBRT	Radiation: WBRT Alone
Arm/Group Description	Participants received topotecan 1.1 milligrams per meters squared per day (mg/m2/day), orally followed approximately 2 hours later by whole-brain radiation therapy (WBRT) 3 Gray (Gy)/day to midline over the course of 10 days. After a 2-week washout period, participants completing chemoradiation and willing to participate in the Continuation Phase of the study received oral topotecan 2.3 mg/m2/day for 5 days, every 21 days, as monotherapy provided the baseline hematologic requirements were met. Monotherapy continued until disease progression or discontinuation. Chemoradiation participants choosing not to participate in the Continuation Phase may have received other chemotherapies or best supportive care, as determined by the investigator.	Participants received WBRT 3 Gy/day for 10 days. Participants may have received other chemotherapies or best supportive care, as determined by the investigator.
Measure Participants	230	228
Baseline, normal, n=230, 228	219 92.8%	216 91.5%
Month 1, normal, n=178, 180	171 72.5%	169 71.6%
Month 3, normal, n=109, 107	102 43.2%	92 39%
Baseline, not interfering, n=230, 228	7 3%	9 3.8%
Month 1, not interfering, n=178, 180	5 2.1%	7 3%
Month 3, not interfering, n=109, 107	3 1.3%	8 3.4%
Baseline, interfering, n=230, 228	3 1.3%	3 1.3%
Month 1, interfering, n=178, 180	0 0%	4 1.7%
Month 3, interfering, n=109, 107	3 1.3%	5 2.1%
Baseline, obtundation and stupor, n=230, 228	1 0.4%	0 0%
Month 1, obtundation and stupor, n=178, 180	2 0.8%	0 0%
Month 3, obtundation and stupor, n=109, 107	1 0.4%	2 0.8%

9. Secondary Outcome

Title	Number of Participants With the Indicated Investigator Assessment for the Neurological Sign and Symptom of Headache at Baseline, Month 1, and Month 3
Description	The investigator (per Common Terminology Criteria for Adverse Events [CTCAE], version 3.0) assessed participants for headache and assigned each participant to one of the following categories: absent, Grade (G) 1, G 2, G 3, G 4, and G 5. Grade refers to the severity of the AE. The CTCAE displays G 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: G 1: mild, asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; G 2: moderate, minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental ADL; G 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated, disabling, limiting self care ADL; G 4: life-threatening consequences, urgent intervention indicated; G 5: death related to AE.
Time Frame	Baseline, Month 1, and Month 3

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants who were assessed at the indicated time point were analyzed. If no data are presented for a particular grade at a particular time point, then no participants had an event of that grade at that time point.

Arm/Group Title	Chemoradiation: Topotecan Plus WBRT	Radiation: WBRT Alone
Arm/Group Description	Participants received topotecan 1.1 milligrams per meters squared per day (mg/m2/day), orally followed approximately 2 hours later by whole-brain radiation therapy (WBRT) 3 Gray (Gy)/day to midline over the course of 10 days. After a 2-week washout period, participants completing chemoradiation and willing to participate in the Continuation Phase of the study received oral topotecan 2.3 mg/m2/day for 5 days, every 21 days, as monotherapy provided the baseline hematologic requirements were met. Monotherapy continued until disease progression or discontinuation. Chemoradiation participants choosing not to participate in the Continuation Phase may have received other chemotherapies or best supportive care, as determined by the investigator.	Participants received WBRT 3 Gy/day for 10 days. Participants may have received other chemotherapies or best supportive care, as determined by the investigator.
Measure Participants	230	228
Baseline, absent, n=230, 228	141 59.7%	146 61.9%
Month 1, absent, n=178, 180	126 53.4%	127 53.8%
Month 3, absent, n=109, 107	85 36%	74 31.4%
Baseline, Grade 1, n=230, 228	62 26.3%	55 23.3%
Month 1, Grade 1, n=178, 180	43 18.2%	38 16.1%
Month 3, Grade 1, n=109, 107	17 7.2%	23 9.7%
Baseline, Grade 2, n=230, 228	25 10.6%	23 9.7%
Month 1, Grade 2, n=178, 180	9 3.8%	14 5.9%
Month 3, Grade 2, n=109, 107	7 3%	10 4.2%
Baseline, Grade 3, n=230, 228	2 0.8%	4 1.7%
Month 1, Grade 3, n=178, 180	0 0%	1 0.4%

10. Secondary Outcome

Title	Number of Participants With the Indicated Investigator Assessment for the Neurological Sign and Symptom of Dizziness/Lightheadedness at Baseline, Month 1, and Month 3
Description	The investigator (per CTCAE, version 3.0) assessed participants for dizziness/lightheadedness and assigned each participant to one of the following categories: absent, G 1, G 2, G 3, G 4, and G 5. Grade refers to the severity of the AE. The CTCAE displays G 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: G 1: mild, asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; G 2: moderate, minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental ADL; G 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated, disabling, limiting self care ADL; G 4: life-threatening consequences, urgent intervention indicated; G 5: death related to AE.
Time Frame	Baseline, Month 1, and Month 3

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants who were assessed at the indicated time point were analyzed. If no data are presented for a particular grade at a particular time point, then no participants had an event of that grade at that time point.

Arm/Group Title	Chemoradiation: Topotecan Plus WBRT	Radiation: WBRT Alone
Arm/Group Description	Participants received topotecan 1.1 milligrams per meters squared per day (mg/m2/day), orally followed approximately 2 hours later by whole-brain radiation therapy (WBRT) 3 Gray (Gy)/day to midline over the course of 10 days. After a 2-week washout period, participants completing chemoradiation and willing to participate in the Continuation Phase of the study received oral topotecan 2.3 mg/m2/day for 5 days, every 21 days, as monotherapy provided the baseline hematologic requirements were met. Monotherapy continued until disease progression or discontinuation. Chemoradiation participants choosing not to participate in the Continuation Phase may have received other chemotherapies or best supportive care, as determined by the investigator.	Participants received WBRT 3 Gy/day for 10 days. Participants may have received other chemotherapies or best supportive care, as determined by the investigator.
Measure Participants	230	228
Baseline, absent, n=230, 228	160 67.8%	151 64%
Month 1, absent, n=178, 180	124 52.5%	128 54.2%
Month 3, absent, n=109, 107	76 32.2%	76 32.2%
Baseline, Grade 1, n=230, 228	45 19.1%	47 19.9%
Month 1, Grade 1, n=178, 180	44 18.6%	36 15.3%
Month 3, Grade 1, n=109, 107	21 8.9%	20 8.5%
Baseline, Grade 2, n=230, 228	21 8.9%	26 11%
Month 1, Grade 2, n=178, 180	7 3%	14 5.9%
Month 3, Grade 2, n=109, 107	9 3.8%	9 3.8%
Baseline, Grade 3, n=230, 228	4 1.7%	4 1.7%
Month 1, Grade 3, n=178, 180	3 1.3%	2 0.8%
Month 3, Grade 3, n=109, 107	3 1.3%	2 0.8%

11. Secondary Outcome

Title	Number of Participants With the Indicated Investigator Assessment for the Neurological Sign and Symptom of Vertigo at Baseline, Month 1, and Month 3
Description	The investigator (per CTCAE, version 3.0) assessed participants for vertigo and assigned each participant to one of the following categories: absent, G 1, G 2, G 3, G 4, and G 5. Grade refers to the severity of the AE. The CTCAE displays G 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: G 1: mild, asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; G 2: moderate, minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental ADL; G 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated, disabling, limiting self care ADL; G 4: life-threatening consequences, urgent intervention indicated; G 5: death related to AE.
Time Frame	Baseline, Month 1, and Month 3

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants who were assessed at the indicated time point were analyzed. If no data are presented for a particular grade at a particular time point, then no participants had an event of that grade at that time point.

Arm/Group Title	Chemoradiation: Topotecan Plus WBRT	Radiation: WBRT Alone
Arm/Group Description	Participants received topotecan 1.1 milligrams per meters squared per day (mg/m2/day), orally followed approximately 2 hours later by whole-brain radiation therapy (WBRT) 3 Gray (Gy)/day to midline over the course of 10 days. After a 2-week washout period, participants completing chemoradiation and willing to participate in the Continuation Phase of the study received oral topotecan 2.3 mg/m2/day for 5 days, every 21 days, as monotherapy provided the baseline hematologic requirements were met. Monotherapy continued until disease progression or discontinuation. Chemoradiation participants choosing not to participate in the Continuation Phase may have received other chemotherapies or best supportive care, as determined by the investigator.	Participants received WBRT 3 Gy/day for 10 days. Participants may have received other chemotherapies or best supportive care, as determined by the investigator.
Measure Participants	230	228
Baseline, absent, n=230, 228	180 76.3%	173 73.3%
Month 1, absent, n=178, 180	148 62.7%	150 63.6%
Month 3, absent, n=109, 107	90 38.1%	86 36.4%
Baseline, Grade 1, n=230, 228	26 11%	30 12.7%
Month 1, Grade 1, n=178, 180	19 8.1%	19 8.1%
Month 3, Grade 1, n=109, 107	14 5.9%	13 5.5%
Baseline, Grade 2, n=230, 228	19 8.1%	22 9.3%
Month 1, Grade 2, n=178, 180	7 3%	9 3.8%
Month 3, Grade 2, n=109, 107	4 1.7%	6 2.5%
Baseline, Grade 3, n=230, 228	5 2.1%	3 1.3%
Month 1, Grade 3, n=178, 180	3 1.3%	2 0.8%
Month 3, Grade 3, n=109, 107	1 0.4%	2 0.8%
Month 1, Grade 4, n=178, 180	1 0.4%	0 0%

12. Secondary Outcome

Title	Number of Participants With the Indicated Investigator Assessment for the Neurological Sign and Symptom of Nausea/Vomiting at Baseline, Month 1, and Month 3
Description	The investigator (per CTCAE, version 3.0) assessed participants for nausea/vomiting and assigned each participant to one of the following categories: absent, G 1, G 2, G 3, G 4, and G 5. Grade refers to the severity of the AE. The CTCAE displays G 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: G 1: mild, asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; G 2: moderate, minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental ADL; G 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated, disabling, limiting self care ADL; G 4: life-threatening consequences, urgent intervention indicated; G 5: death related to AE.
Time Frame	Baseline, Month 1, and Month 3

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants who were assessed at the indicated time point were analyzed. If no data are presented for a particular grade at a particular time point, then no participants had an event of that grade at that time point.

Arm/Group Title	Chemoradiation: Topotecan Plus WBRT	Radiation: WBRT Alone
Arm/Group Description	Participants received topotecan 1.1 milligrams per meters squared per day (mg/m2/day), orally followed approximately 2 hours later by whole-brain radiation therapy (WBRT) 3 Gray (Gy)/day to midline over the course of 10 days. After a 2-week washout period, participants completing chemoradiation and willing to participate in the Continuation Phase of the study received oral topotecan 2.3 mg/m2/day for 5 days, every 21 days, as monotherapy provided the baseline hematologic requirements were met. Monotherapy continued until disease progression or discontinuation. Chemoradiation participants choosing not to participate in the Continuation Phase may have received other chemotherapies or best supportive care, as determined by the investigator.	Participants received WBRT 3 Gy/day for 10 days. Participants may have received other chemotherapies or best supportive care, as determined by the investigator.
Measure Participants	230	228
Baseline, absent, n=230, 228	203 86%	192 81.4%
Month 1, absent, n=178, 180	151 64%	162 68.6%
Month 3, absent, n=109, 107	88 37.3%	93 39.4%
Baseline, Grade 1, n=230, 228	19 8.1%	22 9.3%
Month 1, Grade 1, n=178, 180	20 8.5%	15 6.4%
Month 3, Grade 1, n=109, 107	14 5.9%	11 4.7%
Baseline, Grade 2, n=230, 228	7 3%	10 4.2%
Month 1, Grade 2, n=178, 180	6 2.5%	3 1.3%
Month 3, Grade 2, n=109, 107	6 2.5%	3 1.3%
Baseline, Grade 3, n=230, 228	1 0.4%	4 1.7%
Month 1, Grade 3, n=178, 180	1 0.4%	0 0%
Month 3, Grade 5, n=109, 107	1 0.4%	0 0%

13. Secondary Outcome

Title	Number of Participants With the Indicated Investigator Assessment for the Neurological Sign and Symptom of Visual Problem at Baseline, Month 1, and Month 3
Description	The investigator (per CTCAE, version 3.0) assessed participants for visual problem and assigned each participant to one of the following categories: absent, G 1, G 2, G 3, G 4, and G 5. Grade refers to the severity of the AE. The CTCAE displays G 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: G 1: mild, asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; G 2: moderate, minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental ADL; G 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated, disabling, limiting self care ADL; G 4: life-threatening consequences, urgent intervention indicated; G 5: death related to AE.
Time Frame	Baseline, Month 1, and Month 3

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants who were assessed at the indicated time point were analyzed. If no data are presented for a particular grade at a particular time point, then no participants had an event of that grade at that time point.

Arm/Group Title	Chemoradiation: Topotecan Plus WBRT	Radiation: WBRT Alone
Arm/Group Description	Participants received topotecan 1.1 milligrams per meters squared per day (mg/m2/day), orally followed approximately 2 hours later by whole-brain radiation therapy (WBRT) 3 Gray (Gy)/day to midline over the course of 10 days. After a 2-week washout period, participants completing chemoradiation and willing to participate in the Continuation Phase of the study received oral topotecan 2.3 mg/m2/day for 5 days, every 21 days, as monotherapy provided the baseline hematologic requirements were met. Monotherapy continued until disease progression or discontinuation. Chemoradiation participants choosing not to participate in the Continuation Phase may have received other chemotherapies or best supportive care, as determined by the investigator.	Participants received WBRT 3 Gy/day for 10 days. Participants may have received other chemotherapies or best supportive care, as determined by the investigator.
Measure Participants	230	228
Baseline, absent, n=230, 228	181 76.7%	189 80.1%
Month 1, absent, n=178, 180	148 62.7%	154 65.3%
Month 3, absent, n=109, 107	93 39.4%	93 39.4%
Baseline, Grade 1, n=230, 228	22 9.3%	25 10.6%
Month 1, Grade 1, n=178, 180	16 6.8%	19 8.1%
Month 3, Grade 1, n=109, 107	12 5.1%	10 4.2%
Baseline, Grade 2, n=230, 228	20 8.5%	13 5.5%
Month 1, Grade 2, n=178, 180	11 4.7%	6 2.5%
Month 3, Grade 2, n=109, 107	4 1.7%	3 1.3%
Baseline, Grade 3, n=230, 228	5 2.1%	1 0.4%
Month 1, Grade 3, n=178, 180	2 0.8%	1 0.4%
Month 3, Grade 3, n=109, 107	0 0%	1 0.4%
Baseline, Grade 4, n=230, 228	2 0.8%	0 0%
Month 1, Grade 4, n=178, 180	1 0.4%	0 0%

14. Secondary Outcome

Title	Number of Participants With the Indicated Investigator Assessment for the Neurological Sign and Symptom of Seizure at Baseline, Month 1, and Month 3
Description	The investigator (per CTCAE, version 3.0) assessed participants for seizure and assigned each participant to one of the following categories: absent, G 1, G 2, G 3, G 4, and G 5. Grade refers to the severity of the AE. The CTCAE displays G 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: G 1: mild, asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; G 2: moderate, minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental ADL; G 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated, disabling, limiting self care ADL; G 4: life-threatening consequences, urgent intervention indicated; G 5: death related to AE.
Time Frame	Baseline, Month 1, and Month 3

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants who were assessed at the indicated time point were analyzed. If no data are presented for a particular grade at a particular time point, then no participants had an event of that grade at that time point.

Arm/Group Title	Chemoradiation: Topotecan Plus WBRT	Radiation: WBRT Alone
Arm/Group Description	Participants received topotecan 1.1 milligrams per meters squared per day (mg/m2/day), orally followed approximately 2 hours later by whole-brain radiation therapy (WBRT) 3 Gray (Gy)/day to midline over the course of 10 days. After a 2-week washout period, participants completing chemoradiation and willing to participate in the Continuation Phase of the study received oral topotecan 2.3 mg/m2/day for 5 days, every 21 days, as monotherapy provided the baseline hematologic requirements were met. Monotherapy continued until disease progression or discontinuation. Chemoradiation participants choosing not to participate in the Continuation Phase may have received other chemotherapies or best supportive care, as determined by the investigator.	Participants received WBRT 3 Gy/day for 10 days. Participants may have received other chemotherapies or best supportive care, as determined by the investigator.
Measure Participants	230	228
Baseline, absent, n=230, 228	218 92.4%	216 91.5%
Month 1, absent, n=178, 180	175 74.2%	178 75.4%
Month 3, absent, n=109, 107	109 46.2%	101 42.8%
Baseline, Grade 1, n=230, 228	4 1.7%	6 2.5%
Month 1, Grade 1, n=178, 180	2 0.8%	1 0.4%
Month 3, Grade 1, n=109, 107	0 0%	4 1.7%
Baseline, Grade 2, n=230, 228	6 2.5%	6 2.5%
Month 1, Grade 2, n=178, 180	1 0.4%	1 0.4%
Month 3, Grade 2, n=109, 107	0 0%	2 0.8%
Baseline, Grade 3, n=230, 228	1 0.4%	0 0%
Baseline, Grade 4, n=230, 228	1 0.4%	0 0%

15. Secondary Outcome

Title	Number of Participants With the Indicated Investigator Assessment for the Neurological Sign and Symptom of Other Neurological Symptoms at Baseline, Month 1, and Month 3
Description	The investigator (per CTCAE, version 3.0) assessed participants for other neurological symptoms and assigned each participant to one of the following categories: absent, G 1, G 2, G 3, G 4, and G 5. Grade refers to the severity of the AE. The CTCAE displays G 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: G 1: mild, asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; G 2: moderate, minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental ADL; G 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated, disabling, limiting self care ADL; G 4: life-threatening consequences, urgent intervention indicated; G 5: death related to AE.
Time Frame	Baseline, Month 1, and Month 3

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants who were assessed at the indicated time point were analyzed. If no data are presented for a particular grade at a particular time point, then no participants had an event of that grade at that time point.

Arm/Group Title	Chemoradiation: Topotecan Plus WBRT	Radiation: WBRT Alone
Arm/Group Description	Participants received topotecan 1.1 milligrams per meters squared per day (mg/m2/day), orally followed approximately 2 hours later by whole-brain radiation therapy (WBRT) 3 Gray (Gy)/day to midline over the course of 10 days. After a 2-week washout period, participants completing chemoradiation and willing to participate in the Continuation Phase of the study received oral topotecan 2.3 mg/m2/day for 5 days, every 21 days, as monotherapy provided the baseline hematologic requirements were met. Monotherapy continued until disease progression or discontinuation. Chemoradiation participants choosing not to participate in the Continuation Phase may have received other chemotherapies or best supportive care, as determined by the investigator.	Participants received WBRT 3 Gy/day for 10 days. Participants may have received other chemotherapies or best supportive care, as determined by the investigator.
Measure Participants	229	228
Baseline, absent, n=229, 228	219 92.8%	214 90.7%
Month 1, absent, n=177, 180	165 69.9%	171 72.5%
Month 3, absent, n=109, 107	99 41.9%	101 42.8%
Baseline, Grade 1, n=229, 228	2 0.8%	5 2.1%
Month 1, Grade 1, n=177, 180	2 0.8%	6 2.5%
Month 3, Grade 1, n=109, 107	6 2.5%	5 2.1%
Baseline, Grade 2, n=229, 228	7 3%	8 3.4%
Month 1, Grade 2, n=177, 180	8 3.4%	1 0.4%
Month 3, Grade 2, n=109, 107	3 1.3%	1 0.4%
Baseline, Grade 3, n=229, 228	1 0.4%	1 0.4%
Month 1, Grade 3, n=177, 180	2 0.8%	1 0.4%
Month 1, Grade 4, n=177, 180	0 0%	1 0.4%
Month 3, Grade 5, n=109, 107	1 0.4%	0 0%

16. Secondary Outcome

Title	Number of Participants With the Indicated Investigator Assessment of Cranial Nerves II-XII at Baseline, Month 1, and Month 3
Description	The investigator assessed participants' status of cranial nerves II-XII and assigned each participant to one of the following categories: normal; present, not interfering with ADLs; present, interfering with ADLs; life threatening, disabling.
Time Frame	Baseline, Month 1, and Month 3

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants who were assessed at the indicated time point were analyzed. If no data are presented for a particular status at a particular time point, then no participants had that status at that time point.

Arm/Group Title	Chemoradiation: Topotecan Plus WBRT	Radiation: WBRT Alone
Arm/Group Description	Participants received topotecan 1.1 milligrams per meters squared per day (mg/m2/day), orally followed approximately 2 hours later by whole-brain radiation therapy (WBRT) 3 Gray (Gy)/day to midline over the course of 10 days. After a 2-week washout period, participants completing chemoradiation and willing to participate in the Continuation Phase of the study received oral topotecan 2.3 mg/m2/day for 5 days, every 21 days, as monotherapy provided the baseline hematologic requirements were met. Monotherapy continued until disease progression or discontinuation. Chemoradiation participants choosing not to participate in the Continuation Phase may have received other chemotherapies or best supportive care, as determined by the investigator.	Participants received WBRT 3 Gy/day for 10 days. Participants may have received other chemotherapies or best supportive care, as determined by the investigator.
Measure Participants	229	225
Baseline, normal, n=229, 225	218 92.4%	211 89.4%
Month 1, normal, n=177, 179	172 72.9%	169 71.6%
Month 3, normal, n=109, 107	106 44.9%	102 43.2%
Baseline, present, not interfering, n=229, 225	11 4.7%	10 4.2%
Month 1, present, not interfering, n=177, 179	4 1.7%	6 2.5%
Month 3, present, not interfering, n=109, 107	3 1.3%	2 0.8%
Baseline, present, interfering, n=229, 225	0 0%	4 1.7%
Month 1, present, interfering, n=177, 179	1 0.4%	4 1.7%
Month 3, present, interfering, n=109, 107	0 0%	3 1.3%

17. Secondary Outcome

Title	Number of Participants With the Indicated Investigator Assessment of Language (Dysphasia or Aphasia) at Baseline, Month 1, and Month 3
Description	The investigator assessed participants' status of language (dysphasia or aphasia) and assigned each participant to one of the following categories: absent; awareness of receptive or expressive aphasia, not impairing ability to communicate (not impaired); receptive or expressive dysphasia, impairing ability to communicate (impaired); inability to communicate (unable).
Time Frame	Baseline, Month 1, and Month 3

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants who were assessed at the indicated time point were analyzed. If no data are presented for a particular status at a particular time point, then no participants had that status at that time point.

Arm/Group Title	Chemoradiation: Topotecan Plus WBRT	Radiation: WBRT Alone
Arm/Group Description	Participants received topotecan 1.1 milligrams per meters squared per day (mg/m2/day), orally followed approximately 2 hours later by whole-brain radiation therapy (WBRT) 3 Gray (Gy)/day to midline over the course of 10 days. After a 2-week washout period, participants completing chemoradiation and willing to participate in the Continuation Phase of the study received oral topotecan 2.3 mg/m2/day for 5 days, every 21 days, as monotherapy provided the baseline hematologic requirements were met. Monotherapy continued until disease progression or discontinuation. Chemoradiation participants choosing not to participate in the Continuation Phase may have received other chemotherapies or best supportive care, as determined by the investigator.	Participants received WBRT 3 Gy/day for 10 days. Participants may have received other chemotherapies or best supportive care, as determined by the investigator.
Measure Participants	230	228
Baseline, absent, n=230, 228	211 89.4%	215 91.1%
Month 1, absent, n=178, 180	169 71.6%	173 73.3%
Month 3, absent, n=109, 107	105 44.5%	98 41.5%
Baseline, not impaired, n=230, 228	15 6.4%	10 4.2%
Month 1, not impaired, n=178, 180	6 2.5%	5 2.1%
Month 3, not impaired, n=109, 107	3 1.3%	7 3%
Baseline, impaired, n=230, 228	3 1.3%	3 1.3%
Month 1, impaired, n=178, 180	3 1.3%	2 0.8%
Month 3, impaired, n=109, 107	1 0.4%	0 0%
Baseline, unable, n=230, 228	1 0.4%	0 0%
Month 3, unable, n=109, 107	0 0%	2 0.8%

18. Secondary Outcome

Title	Number of Participants With the Indicated Investigator Assessment of Strength (Right Upper Extremity) at Baseline, Month 1, and Month 3
Description	The investigator assessed participants' status of strength (right upper extremity) and assigned each participant to one of the following categories: normal; Grade 1, asymptomatic with weakness on physical examination; Grade 2, symptomatic and interfering with function, but not interfering with ADLs; Grade 3, symptomatic and interfering with ADLs; Grade 4: bedridden or disabling.
Time Frame	Baseline, Month 1, and Month 3

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants who were assessed at the indicated time point were analyzed. If no data are presented for a particular status at a particular time point, then no participants had that status at that time point.

Arm/Group Title	Chemoradiation: Topotecan Plus WBRT	Radiation: WBRT Alone
Arm/Group Description	Participants received topotecan 1.1 milligrams per meters squared per day (mg/m2/day), orally followed approximately 2 hours later by whole-brain radiation therapy (WBRT) 3 Gray (Gy)/day to midline over the course of 10 days. After a 2-week washout period, participants completing chemoradiation and willing to participate in the Continuation Phase of the study received oral topotecan 2.3 mg/m2/day for 5 days, every 21 days, as monotherapy provided the baseline hematologic requirements were met. Monotherapy continued until disease progression or discontinuation. Chemoradiation participants choosing not to participate in the Continuation Phase may have received other chemotherapies or best supportive care, as determined by the investigator.	Participants received WBRT 3 Gy/day for 10 days. Participants may have received other chemotherapies or best supportive care, as determined by the investigator.
Measure Participants	230	228
Baseline, normal, n=230, 228	203 86%	195 82.6%
Month 1, normal, n=178, 179	153 64.8%	159 67.4%
Month 3, normal, n=109, 107	93 39.4%	89 37.7%
Baseline, Grade 1, n=230, 228	15 6.4%	16 6.8%
Month 1, Grade 1, n=178, 179	13 5.5%	12 5.1%
Month 3, Grade 1, n=109, 107	10 4.2%	10 4.2%
Baseline, Grade 2, n=230, 228	6 2.5%	12 5.1%
Month 1, Grade 2, n=178, 179	6 2.5%	5 2.1%
Month 3, Grade 2, n=109, 107	4 1.7%	5 2.1%
Baseline, Grade 3, n=230, 228	5 2.1%	5 2.1%
Month 1, Grade 3, n=178, 179	4 1.7%	2 0.8%
Month 3, Grade 3, n=109, 107	2 0.8%	3 1.3%
Baseline, Grade 4, n=230, 228	1 0.4%	0 0%
Month 1, Grade 4, n=178, 179	2 0.8%	1 0.4%

19. Secondary Outcome

Title	Number of Participants With the Indicated Investigator Assessment of Strength (Left Upper Extremity) at Baseline, Month 1, and Month 3
Description	The investigator assessed participants' status of strength (left upper extremity) and assigned each participant to one of the following categories: normal; Grade 1, asymptomatic with weakness on physical examination; Grade 2, symptomatic and interfering with function, but not interfering with ADLs; Grade 3, symptomatic and interfering with ADLs; Grade 4: bedridden or disabling.
Time Frame	Baseline, Month 1, and Month 3

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants who were assessed at the indicated time point were analyzed. If no data are presented for a particular status at a particular time point, then no participants had that status at that time point.

Arm/Group Title	Chemoradiation: Topotecan Plus WBRT	Radiation: WBRT Alone
Arm/Group Description	Participants received topotecan 1.1 milligrams per meters squared per day (mg/m2/day), orally followed approximately 2 hours later by whole-brain radiation therapy (WBRT) 3 Gray (Gy)/day to midline over the course of 10 days. After a 2-week washout period, participants completing chemoradiation and willing to participate in the Continuation Phase of the study received oral topotecan 2.3 mg/m2/day for 5 days, every 21 days, as monotherapy provided the baseline hematologic requirements were met. Monotherapy continued until disease progression or discontinuation. Chemoradiation participants choosing not to participate in the Continuation Phase may have received other chemotherapies or best supportive care, as determined by the investigator.	Participants received WBRT 3 Gy/day for 10 days. Participants may have received other chemotherapies or best supportive care, as determined by the investigator.
Measure Participants	230	228
Baseline, normal, n=230, 228	197 83.5%	202 85.6%
Month 1, normal, n=178, 179	149 63.1%	157 66.5%
Month 3, normal, n=109, 107	90 38.1%	86 36.4%
Baseline, Grade 1, n=230, 228	16 6.8%	13 5.5%
Month 1, Grade 1, n=178, 179	16 6.8%	13 5.5%
Month 3, Grade 1, n=109, 107	10 4.2%	11 4.7%
Baseline, Grade 2, n=230, 228	11 4.7%	8 3.4%
Month 1, Grade 2, n=178, 179	8 3.4%	5 2.1%
Month 3, Grade 2, n=109, 107	6 2.5%	5 2.1%
Baseline, Grade 3, n=230, 228	6 2.5%	4 1.7%
Month 1, Grade 3, n=178, 179	3 1.3%	2 0.8%
Month 3, Grade 3, n=109, 107	3 1.3%	4 1.7%
Baseline, Grade 4, n=230, 228	0 0%	1 0.4%
Month 1, Grade 4, n=178, 179	2 0.8%	2 0.8%
Month 3, Grade 4, n=109, 107	0 0%	1 0.4%

20. Secondary Outcome

Title	Number of Participants With the Indicated Investigator Assessment of Strength (Right Lower Extremity) at Baseline, Month 1, and Month 3
Description	The investigator assessed participants' status of strength (right lower extremity) and assigned each participant to one of the following categories: normal; Grade 1, asymptomatic with weakness on physical examination; Grade 2, symptomatic and interfering with function, but not interfering with ADLs; Grade 3, symptomatic and interfering with ADLs; Grade 4: bedridden or disabling.
Time Frame	Baseline, Month 1, and Month 3

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants who were assessed at the indicated time point were analyzed. If no data are presented for a particular status at a particular time point, then no participants had that status at that time point.

Arm/Group Title	Chemoradiation: Topotecan Plus WBRT	Radiation: WBRT Alone
Arm/Group Description	Participants received topotecan 1.1 milligrams per meters squared per day (mg/m2/day), orally followed approximately 2 hours later by whole-brain radiation therapy (WBRT) 3 Gray (Gy)/day to midline over the course of 10 days. After a 2-week washout period, participants completing chemoradiation and willing to participate in the Continuation Phase of the study received oral topotecan 2.3 mg/m2/day for 5 days, every 21 days, as monotherapy provided the baseline hematologic requirements were met. Monotherapy continued until disease progression or discontinuation. Chemoradiation participants choosing not to participate in the Continuation Phase may have received other chemotherapies or best supportive care, as determined by the investigator.	Participants received WBRT 3 Gy/day for 10 days. Participants may have received other chemotherapies or best supportive care, as determined by the investigator.
Measure Participants	230	228
Baseline, normal, n=230, 228	196 83.1%	189 80.1%
Month 1, normal, n=178, 180	137 58.1%	145 61.4%
Month 3, normal, n=109, 107	81 34.3%	80 33.9%
Baseline, Grade 1, n=230, 228	20 8.5%	19 8.1%
Month 1, Grade 1, n=178, 180	17 7.2%	15 6.4%
Month 3, Grade 1, n=109, 107	12 5.1%	11 4.7%
Baseline, Grade 2, n=230, 228	9 3.8%	16 6.8%
Month 1, Grade 2, n=178, 180	11 4.7%	19 8.1%
Month 3, Grade 2, n=109, 107	11 4.7%	11 4.7%
Baseline, Grade 3, n=230, 228	3 1.3%	4 1.7%
Month 1, Grade 3, n=178, 180	9 3.8%	0 0%
Month 3, Grade 3, n=109, 107	4 1.7%	3 1.3%
Baseline, Grade 4, n=230, 228	2 0.8%	0 0%
Month 1, Grade 4, n=178, 180	4 1.7%	1 0.4%
Month 3, Grade 4, n=109, 107	1 0.4%	2 0.8%

21. Secondary Outcome

Title	Number of Participants With the Indicated Investigator Assessment of Strength (Left Lower Extremity) at Baseline, Month 1, and Month 3
Description	The investigator assessed participants' status of strength (left lower extremity) and assigned each participant to one of the following categories: normal; Grade 1, asymptomatic with weakness on physical examination; Grade 2, symptomatic and interfering with function, but not interfering with ADLs; Grade 3, symptomatic and interfering with ADLs; Grade 4: bedridden or disabling.
Time Frame	Baseline, Month 1, and Month 3

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants who were assessed at the indicated time point were analyzed. If no data are presented for a particular status at a particular time point, then no participants had that status at that time point.

Arm/Group Title	Chemoradiation: Topotecan Plus WBRT	Radiation: WBRT Alone
Arm/Group Description	Participants received topotecan 1.1 milligrams per meters squared per day (mg/m2/day), orally followed approximately 2 hours later by whole-brain radiation therapy (WBRT) 3 Gray (Gy)/day to midline over the course of 10 days. After a 2-week washout period, participants completing chemoradiation and willing to participate in the Continuation Phase of the study received oral topotecan 2.3 mg/m2/day for 5 days, every 21 days, as monotherapy provided the baseline hematologic requirements were met. Monotherapy continued until disease progression or discontinuation. Chemoradiation participants choosing not to participate in the Continuation Phase may have received other chemotherapies or best supportive care, as determined by the investigator.	Participants received WBRT 3 Gy/day for 10 days. Participants may have received other chemotherapies or best supportive care, as determined by the investigator.
Measure Participants	230	228
Baseline, normal, n=230, 228	182 77.1%	190 80.5%
Month 1, normal, n=178, 179	128 54.2%	143 60.6%
Month 3, normal, n=109, 107	76 32.2%	73 30.9%
Baseline, Grade 1, n=230, 228	28 11.9%	18 7.6%
Month 1, Grade 1, n=178, 179	26 11%	13 5.5%
Month 3, Grade 1, n=109, 107	11 4.7%	11 4.7%
Baseline, Grade 2, n=230, 228	15 6.4%	15 6.4%
Month 1, Grade 2, n=178, 179	11 4.7%	17 7.2%
Month 3, Grade 2, n=109, 107	14 5.9%	14 5.9%
Baseline, Grade 3, n=230, 228	4 1.7%	3 1.3%
Month 1, Grade 3, n=178, 179	10 4.2%	4 1.7%
Month 3, Grade 3, n=109, 107	6 2.5%	5 2.1%
Baseline, Grade 4, n=230, 228	1 0.4%	2 0.8%
Month 1, Grade 4, n=178, 179	3 1.3%	2 0.8%
Month 3, Grade 4, n=109, 107	2 0.8%	4 1.7%

22. Secondary Outcome

Title	Number of Participants With the Indicated Investigator Assessment of Sensation at Baseline, Month 1, and Month 3
Description	The investigator assessed participants' status of sensation and assigned each participant to one of the following categories: normal; loss of deep tendon reflexes or paresthesia, but not interfering with function (not interfering with function); objective sensory loss or paresthesia interfering with function, but not interfering with ADLs (interfering with function); sensory loss or paresthesia interfering with ADLs (intefering with ADLs); permanent sensory loss that interferes with function (permanent sensory loss).
Time Frame	Baseline, Month 1, and Month 3

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants who were assessed at the indicated time point were analyzed. If no data are presented for a particular status at a particular time point, then no participants had that status at that time point.

Arm/Group Title	Chemoradiation: Topotecan Plus WBRT	Radiation: WBRT Alone
Arm/Group Description	Participants received topotecan 1.1 milligrams per meters squared per day (mg/m2/day), orally followed approximately 2 hours later by whole-brain radiation therapy (WBRT) 3 Gray (Gy)/day to midline over the course of 10 days. After a 2-week washout period, participants completing chemoradiation and willing to participate in the Continuation Phase of the study received oral topotecan 2.3 mg/m2/day for 5 days, every 21 days, as monotherapy provided the baseline hematologic requirements were met. Monotherapy continued until disease progression or discontinuation. Chemoradiation participants choosing not to participate in the Continuation Phase may have received other chemotherapies or best supportive care, as determined by the investigator.	Participants received WBRT 3 Gy/day for 10 days. Participants may have received other chemotherapies or best supportive care, as determined by the investigator.
Measure Participants	230	228
Baseline (BL), normal, n=230, 228	197 83.5%	192 81.4%
Month (M) 1, normal, n=178, 180	144 61%	159 67.4%
Month 3, normal, n=109, 107	100 42.4%	94 39.8%
BL, not interfering with function, n=230, 228	26 11%	26 11%
M 1, not interfering with function, n=178, 180	22 9.3%	15 6.4%
M 3, not interfering with function, n=109, 107	5 2.1%	9 3.8%
BL, interfering with function, n=230, 228	3 1.3%	6 2.5%
M 1, interfering with function, n=178, 180	7 3%	4 1.7%
M 3, interfering with function, n=109, 107	2 0.8%	2 0.8%
Baseline, interfering with ADLs, n=230, 228	4 1.7%	3 1.3%
Month 1, interfering with ADLs, n=178, 180	5 2.1%	2 0.8%
Month 3, interfering with ADLs, n=109, 107	2 0.8%	2 0.8%
Baseline, permanent sensory loss, n=230, 228	0 0%	1 0.4%

23. Secondary Outcome

Title	Number of Participants With the Indicated Investigator Assessment of Ataxia (Right Upper Extremity: Finger to Nose Testing) at Baseline, Month 1, and Month 3
Description	The investigator assessed participants' status of ataxia (right upper extremity: finger to nose testing) and assigned each participant to one of the following categories: normal; Grade 1, asymptomatic but abnormal on physical examination, and not interfering with function; Grade 2, mild symptoms interfering with function, but not interfering with ADLs; Grade 3, moderate symptoms interfering with ADLs; Grade 4, bedridden or disabling.
Time Frame	Baseline, Month 1, and Month 3

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants who were assessed at the indicated time point were analyzed. If no data are presented for a particular status at a particular time point, then no participants had that status at that time point.

Arm/Group Title	Chemoradiation: Topotecan Plus WBRT	Radiation: WBRT Alone
Arm/Group Description	Participants received topotecan 1.1 milligrams per meters squared per day (mg/m2/day), orally followed approximately 2 hours later by whole-brain radiation therapy (WBRT) 3 Gray (Gy)/day to midline over the course of 10 days. After a 2-week washout period, participants completing chemoradiation and willing to participate in the Continuation Phase of the study received oral topotecan 2.3 mg/m2/day for 5 days, every 21 days, as monotherapy provided the baseline hematologic requirements were met. Monotherapy continued until disease progression or discontinuation. Chemoradiation participants choosing not to participate in the Continuation Phase may have received other chemotherapies or best supportive care, as determined by the investigator.	Participants received WBRT 3 Gy/day for 10 days. Participants may have received other chemotherapies or best supportive care, as determined by the investigator.
Measure Participants	229	228
Baseline, normal, n=229, 228	206 87.3%	198 83.9%
Month 1, normal, 178, 179	166 70.3%	166 70.3%
Month 3, normal, n=109, 107	103 43.6%	95 40.3%
Baseline, Grade 1, n=229, 228	13 5.5%	17 7.2%
Month 1, Grade 1, 178, 179	7 3%	6 2.5%
Month 3, Grade 1, n=109, 107	6 2.5%	5 2.1%
Baseline, Grade 2, n=229, 228	5 2.1%	12 5.1%
Month 1, Grade 2, 178, 179	3 1.3%	6 2.5%
Month 3, Grade 2, n=109, 107	0 0%	5 2.1%
Baseline, Grade 3, n=229, 228	3 1.3%	1 0.4%
Month 3, Grade 3, n=109, 107	0 0%	1 0.4%
Baseline, Grade 4, n=229, 228	2 0.8%	0 0%
Month 1, Grade 4, 178, 179	2 0.8%	1 0.4%
Month 3, Grade 4, n=109, 107	0 0%	1 0.4%

24. Secondary Outcome

Title	Number of Participants With the Indicated Investigator Assessment of Ataxia (Left Upper Extremity: Finger to Nose Testing) at Baseline, Month 1, and Month 3
Description	The investigator assessed participants' status of ataxia (left upper extremity: finger to nose testing) and assigned each participant to one of the following categories: normal; Grade 1, asymptomatic but abnormal on physical examination, and not interfering with function; Grade 2, mild symptoms interfering with function, but not interfering with ADLs; Grade 3, moderate symptoms interfering with ADLs; Grade 4, bedridden or disabling.
Time Frame	Baseline, Month 1, and Month 3

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants who were assessed at the indicated time point were analyzed. If no data are presented for a particular status at a particular time point, then no participants had that status at that time point.

Arm/Group Title	Chemoradiation: Topotecan Plus WBRT	Radiation: WBRT Alone
Arm/Group Description	Participants received topotecan 1.1 milligrams per meters squared per day (mg/m2/day), orally followed approximately 2 hours later by whole-brain radiation therapy (WBRT) 3 Gray (Gy)/day to midline over the course of 10 days. After a 2-week washout period, participants completing chemoradiation and willing to participate in the Continuation Phase of the study received oral topotecan 2.3 mg/m2/day for 5 days, every 21 days, as monotherapy provided the baseline hematologic requirements were met. Monotherapy continued until disease progression or discontinuation. Chemoradiation participants choosing not to participate in the Continuation Phase may have received other chemotherapies or best supportive care, as determined by the investigator.	Participants received WBRT 3 Gy/day for 10 days. Participants may have received other chemotherapies or best supportive care, as determined by the investigator.
Measure Participants	230	227
Baseline, normal, n=230, 227	199 84.3%	201 85.2%
Month 1, normal, n=178, 178	156 66.1%	162 68.6%
Month 3, normal, n=109, 107	97 41.1%	94 39.8%
Baseline, Grade 1, n=230, 227	15 6.4%	13 5.5%
Month 1, Grade 1, n=178, 178	14 5.9%	9 3.8%
Month 3, Grade 1, n=109, 107	10 4.2%	6 2.5%
Baseline, Grade 2, n=230, 227	8 3.4%	7 3%
Month 1, Grade 2, n=178, 178	6 2.5%	3 1.3%
Month 3, Grade 2, n=109, 107	2 0.8%	3 1.3%
Baseline, Grade 3, n=230, 227	8 3.4%	4 1.7%
Month 1, Grade 3, n=178, 178	0 0%	3 1.3%
Month 3, Grade 3, n=109, 107	0 0%	1 0.4%
Baseline, Grade 4, n=230, 227	0 0%	2 0.8%
Month 1, Grade 4, n=178, 178	2 0.8%	1 0.4%
Month 3, Grade 4, n=109, 107	0 0%	3 1.3%

25. Secondary Outcome

Title	Number of Participants With the Indicated Investigator Assessment of Ataxia (Gait) at Baseline, Month 1, and Month 3
Description	The investigator assessed participants' status of ataxia (gait) and assigned each participant to one of the following categories: normal; Grade 1, asymptomatic but abnormal on physical examination, and not interfering with function; Grade 2, mild symptoms interfering with function, but not interfering with ADLs; Grade 3, moderate symptoms interfering with ADLs; Grade 4, bedridden or disabling.
Time Frame	Baseline, Month 1, and Month 3

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants who were assessed at the indicated time point were analyzed. If no data are presented for a particular status at a particular time point, then no participants had that status at that time point.

Arm/Group Title	Chemoradiation: Topotecan Plus WBRT	Radiation: WBRT Alone
Arm/Group Description	Participants received topotecan 1.1 milligrams per meters squared per day (mg/m2/day), orally followed approximately 2 hours later by whole-brain radiation therapy (WBRT) 3 Gray (Gy)/day to midline over the course of 10 days. After a 2-week washout period, participants completing chemoradiation and willing to participate in the Continuation Phase of the study received oral topotecan 2.3 mg/m2/day for 5 days, every 21 days, as monotherapy provided the baseline hematologic requirements were met. Monotherapy continued until disease progression or discontinuation. Chemoradiation participants choosing not to participate in the Continuation Phase may have received other chemotherapies or best supportive care, as determined by the investigator.	Participants received WBRT 3 Gy/day for 10 days. Participants may have received other chemotherapies or best supportive care, as determined by the investigator.
Measure Participants	230	227
Baseline, normal, n=230, 227	172 72.9%	178 75.4%
Month 1, normal, n=178, 179	138 58.5%	147 62.3%
Month 3, normal, n=108, 107	85 36%	76 32.2%
Baseline, Grade 1, n=230, 227	13 5.5%	22 9.3%
Month 1, Grade 1, n=178, 179	16 6.8%	13 5.5%
Month 3, Grade 1, n=108, 107	9 3.8%	10 4.2%
Baseline, Grade 2, n=230, 227	37 15.7%	20 8.5%
Month 1, Grade 2, n=178, 179	14 5.9%	14 5.9%
Month 3, Grade 2, n=108, 107	9 3.8%	12 5.1%
Baseline, Grade 3, n=230, 227	6 2.5%	6 2.5%
Month 1, Grade 3, n=178, 179	7 3%	3 1.3%
Month 3, Grade 3, n=108, 107	4 1.7%	5 2.1%
Baseline, Grade 4, n=230, 227	2 0.8%	1 0.4%
Month 1, Grade 4, n=178, 179	3 1.3%	2 0.8%
Month 3, Grade 4, n=108, 107	1 0.4%	4 1.7%

26. Secondary Outcome

Title	Number of Participants With the Indicated Investigator Assessment of Ataxia (Balance) at Baseline, Month 1, and Month 3
Description	The investigator assessed participants' status of ataxia (balance) and assigned each participant to one of the following categories: normal; Grade 1, asymptomatic but abnormal on physical examination, and not interfering with function; Grade 2, mild symptoms interfering with function, but not interfering with ADLs; Grade 3, moderate symptoms interfering with ADLs; Grade 4, bedridden or disabling.
Time Frame	Baseline, Month 1, and Month 3

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants who were assessed at the indicated time point were analyzed. If no data are presented for a particular status at a particular time point, then no participants had that status at that time point.

Arm/Group Title	Chemoradiation: Topotecan Plus WBRT	Radiation: WBRT Alone
Arm/Group Description	Participants received topotecan 1.1 milligrams per meters squared per day (mg/m2/day), orally followed approximately 2 hours later by whole-brain radiation therapy (WBRT) 3 Gray (Gy)/day to midline over the course of 10 days. After a 2-week washout period, participants completing chemoradiation and willing to participate in the Continuation Phase of the study received oral topotecan 2.3 mg/m2/day for 5 days, every 21 days, as monotherapy provided the baseline hematologic requirements were met. Monotherapy continued until disease progression or discontinuation. Chemoradiation participants choosing not to participate in the Continuation Phase may have received other chemotherapies or best supportive care, as determined by the investigator.	Participants received WBRT 3 Gy/day for 10 days. Participants may have received other chemotherapies or best supportive care, as determined by the investigator.
Measure Participants	230	228
Baseline, normal, n=230, 228	153 64.8%	152 64.4%
Month 1, normal, n=178, 178	131 55.5%	128 54.2%
Month 3, normal, n=108, 107	78 33.1%	75 31.8%
Baseline, Grade 1, n=230, 228	37 15.7%	44 18.6%
Month 1, Grade 1, n=178, 178	23 9.7%	28 11.9%
Month 3, Grade 1, n=108, 107	17 7.2%	13 5.5%
Baseline, Grade 2, n=230, 228	27 11.4%	23 9.7%
Month 1, Grade 2, n=178, 178	13 5.5%	16 6.8%
Month 3, Grade 2, n=108, 107	8 3.4%	9 3.8%
Baseline, Grade 3, n=230, 228	10 4.2%	7 3%
Month 1, Grade 3, n=178, 178	8 3.4%	5 2.1%
Month 3, Grade 3, n=108, 107	4 1.7%	5 2.1%
Baseline, Grade 4, n=230, 228	3 1.3%	2 0.8%
Month 1, Grade 4, n=178, 178	3 1.3%	1 0.4%
Month 3, Grade 4, n=108, 107	1 0.4%	5 2.1%

27. Secondary Outcome

Title	Number of Participants With Any Adverse Event (AE; Both Serious and Non-serious) or Serious Adverse Event (SAE)
Description	An AE is defined as any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life threatening; requires hospitalization or prolongation of existing hospitalization; results in disability/incapacity; is a congenital anomaly/birth defect. For a list of all SAEs and AEs, see the SAE/AE module of this results summary.
Time Frame	From Randomization until the last clinic visit associated with the study, up until 35 days after the start of the last course of treatment (up to 75 weeks)

Outcome Measure Data

Analysis Population Description

Modified ITT Population: all randomized participants who received at least one dose of randomized therapy. Participants were analyzed by the actual treatment received, even if this differed from the treatment to which they were randomized.

Arm/Group Title	Chemoradiation: Topotecan Plus WBRT	Radiation: WBRT Alone
Arm/Group Description	Participants received topotecan 1.1 milligrams per meters squared per day (mg/m2/day), orally followed approximately 2 hours later by whole-brain radiation therapy (WBRT) 3 Gray (Gy)/day to midline over the course of 10 days. After a 2-week washout period, participants completing chemoradiation and willing to participate in the Continuation Phase of the study received oral topotecan 2.3 mg/m2/day for 5 days, every 21 days, as monotherapy provided the baseline hematologic requirements were met. Monotherapy continued until disease progression or discontinuation. Chemoradiation participants choosing not to participate in the Continuation Phase may have received other chemotherapies or best supportive care, as determined by the investigator.	Participants received WBRT 3 Gy/day for 10 days. Participants may have received other chemotherapies or best supportive care, as determined by the investigator.
Measure Participants	235	233
AE	204 86.4%	148 62.7%
SAE	96 40.7%	43 18.2%

28. Secondary Outcome

Title	Number of Participants With the Indicated Worst-case Change From Baseline in the Indicated Chemistry Parameters With Respect to the Normal Range
Description	The worst-case change from Baseline in chemistry parameters was measured as decrease to low (DTL), change to normal or no change (CTN/NC), or increase to high (ITH). The worst-case change value could have been measured at any point during the on-therapy period. Participants are counted twice if the participant "Decreased to Low" and "Increased to High" during the on-therapy period.
Time Frame	From Randomization until the last clinic visit associated with the study, up until 35 days after the start of the last course of treatment (up to 75 weeks)

Outcome Measure Data

Analysis Population Description

Modified ITT Population. Only those participants with available laboratory values (indicated by the "n" in the category titles) were analyzed. Different participants may have been analyzed for different parameters; therefore, the overall number of participants analyzed reflects everyone in the Modified ITT Population.

Arm/Group Title	Chemoradiation: Topotecan Plus WBRT	Radiation: WBRT Alone
Arm/Group Description	Participants received topotecan 1.1 milligrams per meters squared per day (mg/m2/day), orally followed approximately 2 hours later by whole-brain radiation therapy (WBRT) 3 Gray (Gy)/day to midline over the course of 10 days. After a 2-week washout period, participants completing chemoradiation and willing to participate in the Continuation Phase of the study received oral topotecan 2.3 mg/m2/day for 5 days, every 21 days, as monotherapy provided the baseline hematologic requirements were met. Monotherapy continued until disease progression or discontinuation. Chemoradiation participants choosing not to participate in the Continuation Phase may have received other chemotherapies or best supportive care, as determined by the investigator.	Participants received WBRT 3 Gy/day for 10 days. Participants may have received other chemotherapies or best supportive care, as determined by the investigator.
Measure Participants	235	233
Chloride, DTL, n=169, 171	32 13.6%	21 8.9%
Chloride, CTN/NC, n=169, 171	116 49.2%	144 61%
Chloride, ITH, n=169, 171	22 9.3%	6 2.5%
Creatinine clearance, DTL, n=159, 145	26 11%	9 3.8%
Creatinine clearance, CTN/NC, n=159, 145	121 51.3%	134 56.8%
Creatinine clearance, ITH, n=159, 145	15 6.4%	2 0.8%
Lactate dehydrogenase, DTL, n=169, 168	8 3.4%	1 0.4%
Lactate dehydrogenase, CTN/NC, n=169, 168	117 49.6%	127 53.8%
Lactate dehydrogenase, ITH, n=169, 168	47 19.9%	40 16.9%
Total protein, DTL, n=171, 175	48 20.3%	36 15.3%
Total protein, CTN/NC, n=171, 175	119 50.4%	137 58.1%
Total protein, ITH, n=171, 175	4 1.7%	2 0.8%
Urea/blood urea nitrogen, DTL, n=178, 179	7 3%	4 1.7%
Urea/blood urea nitrogen, CTN/NC, n=178, 179	139 58.9%	152 64.4%
Urea/blood urea nitrogen, ITH, n=178, 179	33 14%	24 10.2%
Uric acid, DTL, n=159, 152	21 8.9%	12 5.1%
Uric acid, CTN/NC, n=159, 152	125 53%	134 56.8%
Uric acid, ITH, n=159, 152	13 5.5%	6 2.5%
Basophils, DTL, n=215, 211	7 3%	1 0.4%
Basophils, CTN/NC, n=215, 211	186 78.8%	200 84.7%
Basophils, ITH, n=215, 211	25 10.6%	10 4.2%
Eosinophils, DTL, n=214, 211	28 11.9%	12 5.1%
Eosinophils, CTN/NC, n=214, 211	182 77.1%	191 80.9%
Eosinophils, ITH, n=214, 211	4 1.7%	8 3.4%
Hematocrit, DTL, n=215, 212	98 41.5%	38 16.1%
Hematocrit, CTN/NC, n=215, 212	117 49.6%	169 71.6%
Hematocrit, ITH, n=215, 212	1 0.4%	6 2.5%
Monocytes, DTL, n=216, 212	84 35.6%	17 7.2%
Monocytes, CTN/NC, n=216, 212	119 50.4%	161 68.2%
Monocytes, ITH, n=216, 212	54 22.9%	37 15.7%
Red Blood Cell Count, DTL, n=216, 212	103 43.6%	38 16.1%
Red Blood Cell Count, CTN/NC, n=216, 212	113 47.9%	171 72.5%
Red Blood Cell Count, ITH, n=216, 212	0 0%	4 1.7%

29. Secondary Outcome

Title	Lesion Assessment and Measurement
Description	Lesions were assessed per WHO criteria. For lesion assessment data, see the outcome measure entitled "Number of participants with a complete response (CR) or a partial response (PR) (central nervous system [CNS]-radiologic)."
Time Frame	From the time of Randomization until the time of CR or PR (up to 75 weeks)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Chemoradiation: Topotecan Plus WBRT	Radiation: WBRT Alone
Arm/Group Description	Participants received topotecan 1.1 milligrams per meters squared per day (mg/m2/day), orally followed approximately 2 hours later by whole-brain radiation therapy (WBRT) 3 Gray (Gy)/day to midline over the course of 10 days. After a 2-week washout period, participants completing chemoradiation and willing to participate in the Continuation Phase of the study received oral topotecan 2.3 mg/m2/day for 5 days, every 21 days, as monotherapy provided the baseline hematologic requirements were met. Monotherapy continued until disease progression or discontinuation. Chemoradiation participants choosing not to participate in the Continuation Phase may have received other chemotherapies or best supportive care, as determined by the investigator.	Participants received WBRT 3 Gy/day for 10 days. Participants may have received other chemotherapies or best supportive care, as determined by the investigator.
Measure Participants	0	0

30. Secondary Outcome

Title	Brain Symptoms
Description	Brain symptoms were assessed as the number of participants with neurological signs and symptoms. For brain symptom data, see the outcome measures entitled "Number of participants with the indicated investigator assessment for the neurological sign and symptom of X at Baseline, Month 1, and Month 3."
Time Frame	Baseline, Month 1, and Month 3

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Chemoradiation: Topotecan Plus WBRT	Radiation: WBRT Alone
Arm/Group Description	Participants received topotecan 1.1 milligrams per meters squared per day (mg/m2/day), orally followed approximately 2 hours later by whole-brain radiation therapy (WBRT) 3 Gray (Gy)/day to midline over the course of 10 days. After a 2-week washout period, participants completing chemoradiation and willing to participate in the Continuation Phase of the study received oral topotecan 2.3 mg/m2/day for 5 days, every 21 days, as monotherapy provided the baseline hematologic requirements were met. Monotherapy continued until disease progression or discontinuation. Chemoradiation participants choosing not to participate in the Continuation Phase may have received other chemotherapies or best supportive care, as determined by the investigator.	Participants received WBRT 3 Gy/day for 10 days. Participants may have received other chemotherapies or best supportive care, as determined by the investigator.
Measure Participants	0	0

31. Secondary Outcome

Title	Number of Participants Who Died or Progressed
Description	Disease-related events were measured as the number of participants who died or progressed. Progressive disease (PD) is defined as an increase >=25% in any measurable lesion or, in participants with non-measurable disease only, an estimation of an increase >=25%. In both cases, determination of progression included the appearance of any new lesions, or signification worsening of conditions presumed to be related to malignancy. Participants with clinical or laboratory evidence of possible disease progression were to be evaluated radiologically. Data were analyzed with censoring for extended loss to follow-up to account for two or more missed assessments before an event. The date of the last adequate CNS assessment before extended loss to follow-up was used for censored participants.
Time Frame	From Randomization until the last clinic visit associated with the study, up until 35 days after the start of the last course of treatment (up to 75 weeks)

Outcome Measure Data

Analysis Population Description

mITT Population

Arm/Group Title	Chemoradiation: Topotecan Plus WBRT	Radiation: WBRT Alone
Arm/Group Description	Participants received topotecan 1.1 milligrams per meters squared per day (mg/m2/day), orally followed approximately 2 hours later by whole-brain radiation therapy (WBRT) 3 Gray (Gy)/day to midline over the course of 10 days. After a 2-week washout period, participants completing chemoradiation and willing to participate in the Continuation Phase of the study received oral topotecan 2.3 mg/m2/day for 5 days, every 21 days, as monotherapy provided the baseline hematologic requirements were met. Monotherapy continued until disease progression or discontinuation. Chemoradiation participants choosing not to participate in the Continuation Phase may have received other chemotherapies or best supportive care, as determined by the investigator.	Participants received WBRT 3 Gy/day for 10 days. Participants may have received other chemotherapies or best supportive care, as determined by the investigator.
Measure Participants	235	233
Number [participants]	179 75.8%	161 68.2%

Adverse Events

Adverse Event Reporting Description	Serious adverse events (SAEs) and non-serious AEs were collected in members of the Modified Intent-to-Treat Population, comprised of all randomized participants (par.) who received at least one dose of randomized therapy. Par. were analyzed by the actual treatment received, even if it differed from the treatment to which they were randomized.
Arm/Group Title	Chemoradiation: Topotecan Plus WBRT		Radiation: WBRT Alone
Arm/Group Description	Participants received topotecan 1.1 milligrams per meters squared per day (mg/m2/day), orally followed approximately 2 hours later by whole-brain radiation therapy (WBRT) 3 Gray (Gy)/day to midline over the course of 10 days. After a 2-week washout period, participants completing chemoradiation and willing to participate in the Continuation Phase of the study received oral topotecan 2.3 mg/m2/day for 5 days, every 21 days, as monotherapy provided the baseline hematologic requirements were met. Monotherapy continued until disease progression or discontinuation. Chemoradiation participants choosing not to participate in the Continuation Phase may have received other chemotherapies or best supportive care, as determined by the investigator.		Participants received WBRT 3 Gy/day for 10 days. Participants may have received other chemotherapies or best supportive care, as determined by the investigator.
All Cause Mortality
	Chemoradiation: Topotecan Plus WBRT		Radiation: WBRT Alone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Chemoradiation: Topotecan Plus WBRT		Radiation: WBRT Alone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	96/235 (40.9%)		43/233 (18.5%)
Blood and lymphatic system disorders
Neutropenia	22/235 (9.4%)		2/233 (0.9%)
Thrombocytopenia	22/235 (9.4%)		1/233 (0.4%)
Anaemia	16/235 (6.8%)		1/233 (0.4%)
Febrile neutropenia	13/235 (5.5%)		0/233 (0%)
Leukopenia	8/235 (3.4%)		1/233 (0.4%)
Pancytopenia	6/235 (2.6%)		0/233 (0%)
Agranulocytosis	1/235 (0.4%)		0/233 (0%)
Lymphopenia	1/235 (0.4%)		0/233 (0%)
Cardiac disorders
Atrial fibrillation	1/235 (0.4%)		1/233 (0.4%)
Cardiac failure acute	2/235 (0.9%)		0/233 (0%)
Pericarditis	1/235 (0.4%)		1/233 (0.4%)
Acute myocardial infarction	1/235 (0.4%)		0/233 (0%)
Cardiopulmonary failure	0/235 (0%)		1/233 (0.4%)
Coronary artery insufficiency	1/235 (0.4%)		0/233 (0%)
Myocardial infarction	0/235 (0%)		1/233 (0.4%)
Myocardial ischaemia	1/235 (0.4%)		0/233 (0%)
Endocrine disorders
Adrenal insufficiency	1/235 (0.4%)		0/233 (0%)
Inappropriate antidiuretic hormone secretion	1/235 (0.4%)		0/233 (0%)
Gastrointestinal disorders
Diarrhoea	6/235 (2.6%)		0/233 (0%)
Dyspnoea	3/235 (1.3%)		1/233 (0.4%)
Nausea	3/235 (1.3%)		2/233 (0.9%)
Vomiting	3/235 (1.3%)		0/233 (0%)
Constipation	0/235 (0%)		2/233 (0.9%)
Small intestinal haemorrhage	2/235 (0.9%)		0/233 (0%)
Intestinal obstruction	0/235 (0%)		1/233 (0.4%)
Intestinal perforation	1/235 (0.4%)		0/233 (0%)
Oesophageal stenosis	0/235 (0%)		1/233 (0.4%)
Oropharyngeal pain	1/235 (0.4%)		0/233 (0%)
Pancreatitis	0/235 (0%)		1/233 (0.4%)
General disorders
Asthenia	5/235 (2.1%)		1/233 (0.4%)
Pyrexia	5/235 (2.1%)		1/233 (0.4%)
Disease progression	3/235 (1.3%)		0/233 (0%)
Performance status decreased	2/235 (0.9%)		0/233 (0%)
Fatigue	1/235 (0.4%)		0/233 (0%)
General physical health deterioration	1/235 (0.4%)		0/233 (0%)
Non-cardiac chest pain	0/235 (0%)		1/233 (0.4%)
Oedema peripheral	0/235 (0%)		1/233 (0.4%)
Pain	0/235 (0%)		1/233 (0.4%)
Infections and infestations
Pneumonia	7/235 (3%)		6/233 (2.6%)
Sepsis	4/235 (1.7%)		1/233 (0.4%)
Septic shock	1/235 (0.4%)		2/233 (0.9%)
Bronchitis	1/235 (0.4%)		0/233 (0%)
Cellulitis	0/235 (0%)		1/233 (0.4%)
Herpes zoster	1/235 (0.4%)		0/233 (0%)
Lobar pneumonia	1/235 (0.4%)		0/233 (0%)
Lower respiratory tract infection	0/235 (0%)		1/233 (0.4%)
Lung abscess	1/235 (0.4%)		0/233 (0%)
Oropharyngitis fungal	1/235 (0.4%)		0/233 (0%)
Peridiverticular abscess	1/235 (0.4%)		0/233 (0%)
Upper respiratory tract infection	0/235 (0%)		1/233 (0.4%)
Injury, poisoning and procedural complications
Accidental overdose	2/235 (0.9%)		0/233 (0%)
Overdose	2/235 (0.9%)		0/233 (0%)
Face injury	1/235 (0.4%)		0/233 (0%)
Femoral neck fracture	0/235 (0%)		1/233 (0.4%)
Femur fracture	1/235 (0.4%)		0/233 (0%)
Radiation pneumonitis	0/235 (0%)		1/233 (0.4%)
Investigations
Blood bilirubin increased	1/235 (0.4%)		0/233 (0%)
Blood creatinine increased	1/235 (0.4%)		0/233 (0%)
Weight decreased	1/235 (0.4%)		0/233 (0%)
Metabolism and nutrition disorders
Dehydration	5/235 (2.1%)		3/233 (1.3%)
Hyperglycaemia	1/235 (0.4%)		1/233 (0.4%)
Decreased appetite	1/235 (0.4%)		1/233 (0.4%)
Diabetes mellitus	1/235 (0.4%)		1/233 (0.4%)
Hypernatraemia	1/235 (0.4%)		0/233 (0%)
Hyponatraemia	1/235 (0.4%)		0/233 (0%)
Malnutrition	1/235 (0.4%)		0/233 (0%)
Musculoskeletal and connective tissue disorders
Muscular weakness	1/235 (0.4%)		1/233 (0.4%)
Back pain	0/235 (0%)		1/233 (0.4%)
Musculoskeletal chest pain	1/235 (0.4%)		0/233 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Non-small cell lung cancer	2/235 (0.9%)		0/233 (0%)
Nervous system disorders
Brain oedema	3/235 (1.3%)		0/233 (0%)
Cerebrovascular accident	2/235 (0.9%)		0/233 (0%)
Syncope	2/235 (0.9%)		0/233 (0%)
Convulsion	1/235 (0.4%)		0/233 (0%)
Encephalopathy	1/235 (0.4%)		0/233 (0%)
Grand mal convulsion	0/235 (0%)		1/233 (0.4%)
Headache	1/235 (0.4%)		0/233 (0%)
Hydrocephalus	1/235 (0.4%)		0/233 (0%)
Paraplegia	1/235 (0.4%)		0/233 (0%)
Radiculopathy	1/235 (0.4%)		0/233 (0%)
Psychiatric disorders
Confusional state	2/235 (0.9%)		0/233 (0%)
Mental status changes	1/235 (0.4%)		0/233 (0%)
Renal and urinary disorders
Haematuria	0/235 (0%)		1/233 (0.4%)
Renal failure	0/235 (0%)		1/233 (0.4%)
Urinary retention	0/235 (0%)		1/233 (0.4%)
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	1/235 (0.4%)		4/233 (1.7%)
Chronic obstructive pulmonary disease	3/235 (1.3%)		1/233 (0.4%)
Haemoptysis	1/235 (0.4%)		0/233 (0%)
Respiratory failure	0/235 (0%)		3/233 (1.3%)
Pneumonitis	1/235 (0.4%)		1/233 (0.4%)
Pulmonary haemorrhage	0/235 (0%)		2/233 (0.9%)
Aspiration	0/235 (0%)		1/233 (0.4%)
Bronchial obstruction	1/235 (0.4%)		0/233 (0%)
Hypoxia	0/235 (0%)		1/233 (0.4%)
Lung infiltration	0/235 (0%)		1/233 (0.4%)
Pleurisy	0/235 (0%)		1/233 (0.4%)
Skin and subcutaneous tissue disorders
Stevens-Johnson syndrome	0/235 (0%)		1/233 (0.4%)
Vascular disorders
Deep vein thrombosis	3/235 (1.3%)		1/233 (0.4%)
Arterial thrombosis limb	0/235 (0%)		1/233 (0.4%)
Jugular vein thrombosis	1/235 (0.4%)		0/233 (0%)
Orthostatic hypotension	1/235 (0.4%)		0/233 (0%)
Superior vena cava syndrome	1/235 (0.4%)		0/233 (0%)
Venous thrombosis	0/235 (0%)		1/233 (0.4%)
Other (Not Including Serious) Adverse Events
	Chemoradiation: Topotecan Plus WBRT		Radiation: WBRT Alone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	192/235 (81.7%)		139/233 (59.7%)
Blood and lymphatic system disorders
Anaemia	7/235 (3%)		1/233 (0.4%)
Thrombocytopenia	5/235 (2.1%)		1/233 (0.4%)
Neutropenia	3/235 (1.3%)		0/233 (0%)
Leukopenia	2/235 (0.9%)		0/233 (0%)
Coagulopathy	0/235 (0%)		1/233 (0.4%)
Febrile neutropenia	1/235 (0.4%)		0/233 (0%)
Pancytopenia	1/235 (0.4%)		0/233 (0%)
Cardiac disorders
Atrial fibrillation	3/235 (1.3%)		2/233 (0.9%)
Tachycardia	2/235 (0.9%)		3/233 (1.3%)
Cardiac failure	1/235 (0.4%)		1/233 (0.4%)
Palpitations	2/235 (0.9%)		0/233 (0%)
Angina pectoris	1/235 (0.4%)		0/233 (0%)
Cardiac failure congestive	0/235 (0%)		1/233 (0.4%)
Sinus tachycardia	0/235 (0%)		1/233 (0.4%)
Supraventricular extrasystoles	0/235 (0%)		1/233 (0.4%)
Ear and labyrinth disorders
Vertigo	4/235 (1.7%)		3/233 (1.3%)
Tinnitus	4/235 (1.7%)		0/233 (0%)
Ear pain	2/235 (0.9%)		0/233 (0%)
Ear pruritus	2/235 (0.9%)		0/233 (0%)
Auricular swelling	0/235 (0%)		1/233 (0.4%)
Deafness	0/235 (0%)		1/233 (0.4%)
Hearing impaired	1/235 (0.4%)		0/233 (0%)
Hypoacusis	1/235 (0.4%)		0/233 (0%)
Endocrine disorders
Cushingoid	1/235 (0.4%)		1/233 (0.4%)
Inappropriate antidiuretic hormone secretion	1/235 (0.4%)		0/233 (0%)
Eye disorders
Vision blurred	4/235 (1.7%)		8/233 (3.4%)
Visual acuity reduced	3/235 (1.3%)		2/233 (0.9%)
Visual impairment	2/235 (0.9%)		2/233 (0.9%)
Asthenopia	1/235 (0.4%)		0/233 (0%)
Blindness	0/235 (0%)		1/233 (0.4%)
Conjunctivitis	0/235 (0%)		1/233 (0.4%)
Eye inflammation	1/235 (0.4%)		0/233 (0%)
Eye pain	1/235 (0.4%)		0/233 (0%)
Myopia	1/235 (0.4%)		0/233 (0%)
Retinal vascular disorder	1/235 (0.4%)		0/233 (0%)
Gastrointestinal disorders
Nausea	64/235 (27.2%)		30/233 (12.9%)
Vomiting	37/235 (15.7%)		24/233 (10.3%)
Diarrhoea	19/235 (8.1%)		8/233 (3.4%)
Dyspepsia	17/235 (7.2%)		10/233 (4.3%)
Constipation	8/235 (3.4%)		10/233 (4.3%)
Abdominal pain	4/235 (1.7%)		6/233 (2.6%)
Stomatitis	7/235 (3%)		1/233 (0.4%)
Abdominal pain upper	2/235 (0.9%)		3/233 (1.3%)
Dysphagia	2/235 (0.9%)		3/233 (1.3%)
Dry mouth	2/235 (0.9%)		2/233 (0.9%)
Gastrooesophageal reflux disease	3/235 (1.3%)		0/233 (0%)
Abdominal distension	1/235 (0.4%)		1/233 (0.4%)
Flatulence	2/235 (0.9%)		0/233 (0%)
Mouth ulceration	2/235 (0.9%)		0/233 (0%)
Rectal haemorrhage	1/235 (0.4%)		1/233 (0.4%)
Abdominal discomfort	1/235 (0.4%)		0/233 (0%)
Aphthous stomatitis	0/235 (0%)		1/233 (0.4%)
Ascites	0/235 (0%)		1/233 (0.4%)
Breath odour	0/235 (0%)		1/233 (0.4%)
Faecal incontinence	1/235 (0.4%)		0/233 (0%)
Faeces discoloured	1/235 (0.4%)		0/233 (0%)
Gastritis	0/235 (0%)		1/233 (0.4%)
Gingival pain	1/235 (0.4%)		0/233 (0%)
Glossodynia	1/235 (0.4%)		0/233 (0%)
Haematochezia	1/235 (0.4%)		0/233 (0%)
Haemorrhoids	0/235 (0%)		1/233 (0.4%)
Hyperchlorhydria	1/235 (0.4%)		0/233 (0%)
Oesophageal pain	1/235 (0.4%)		0/233 (0%)
Oral pain	0/235 (0%)		1/233 (0.4%)
Retching	1/235 (0.4%)		0/233 (0%)
General disorders
Fatigue	39/235 (16.6%)		37/233 (15.9%)
Asthenia	29/235 (12.3%)		19/233 (8.2%)
Oedema peripheral	15/235 (6.4%)		15/233 (6.4%)
Pyrexia	13/235 (5.5%)		5/233 (2.1%)
Mucosal inflammation	7/235 (3%)		0/233 (0%)
Gait disturbance	2/235 (0.9%)		4/233 (1.7%)
Face oedema	1/235 (0.4%)		3/233 (1.3%)
Pain	1/235 (0.4%)		3/233 (1.3%)
Chest pain	1/235 (0.4%)		2/233 (0.9%)
Chills	2/235 (0.9%)		1/233 (0.4%)
Non-cardiac chest pain	2/235 (0.9%)		1/233 (0.4%)
Spinal pain	1/235 (0.4%)		1/233 (0.4%)
Chest discomfort	0/235 (0%)		1/233 (0.4%)
Early satiety	1/235 (0.4%)		0/233 (0%)
Gravitational oedema	1/235 (0.4%)		0/233 (0%)
Hyperthermia	0/235 (0%)		1/233 (0.4%)
Influenza like illness	1/235 (0.4%)		0/233 (0%)
Local swelling	0/235 (0%)		1/233 (0.4%)
Localised oedema	0/235 (0%)		1/233 (0.4%)
Malaise	1/235 (0.4%)		0/233 (0%)
Mucosal erosion	1/235 (0.4%)		0/233 (0%)
Oedema	1/235 (0.4%)		0/233 (0%)
Swelling	1/235 (0.4%)		0/233 (0%)
Hepatobiliary disorders
Hepatic function abnormal	1/235 (0.4%)		0/233 (0%)
Infections and infestations
Pneumonia	4/235 (1.7%)		4/233 (1.7%)
Oral candidiasis	5/235 (2.1%)		2/233 (0.9%)
Urinary tract infection	3/235 (1.3%)		4/233 (1.7%)
Candidiasis	3/235 (1.3%)		2/233 (0.9%)
Oral fungal infection	2/235 (0.9%)		3/233 (1.3%)
Oropharyngitis fungal	1/235 (0.4%)		3/233 (1.3%)
Upper respiratory tract infection	3/235 (1.3%)		1/233 (0.4%)
Nasopharyngitis	1/235 (0.4%)		2/233 (0.9%)
Rhinitis	2/235 (0.9%)		1/233 (0.4%)
Bronchitis	0/235 (0%)		2/233 (0.9%)
Cystitis	0/235 (0%)		2/233 (0.9%)
Herpes zoster	0/235 (0%)		2/233 (0.9%)
Influenza	2/235 (0.9%)		0/233 (0%)
Oesophageal candidiasis	2/235 (0.9%)		0/233 (0%)
Oral herpes	2/235 (0.9%)		0/233 (0%)
Oropharyngeal candidiasis	2/235 (0.9%)		0/233 (0%)
Pharyngitis	2/235 (0.9%)		0/233 (0%)
Anal fungal infection	1/235 (0.4%)		0/233 (0%)
Fungal infection	0/235 (0%)		1/233 (0.4%)
Fungal oesophagitis	0/235 (0%)		1/233 (0.4%)
Furuncle	0/235 (0%)		1/233 (0.4%)
Herpes simplex	1/235 (0.4%)		0/233 (0%)
Infection	0/235 (0%)		1/233 (0.4%)
Mastoiditis	0/235 (0%)		1/233 (0.4%)
Orchitis	0/235 (0%)		1/233 (0.4%)
Otitis media	0/235 (0%)		1/233 (0.4%)
Rash pustular	1/235 (0.4%)		0/233 (0%)
Respiratory tract infection	0/235 (0%)		1/233 (0.4%)
Soft tissue infection	1/235 (0.4%)		0/233 (0%)
Tonsillitis	1/235 (0.4%)		0/233 (0%)
Tracheobronchitis	0/235 (0%)		1/233 (0.4%)
Vaginal infection	1/235 (0.4%)		0/233 (0%)
Vulvovaginal mycotic infection	1/235 (0.4%)		0/233 (0%)
Injury, poisoning and procedural complications
Fall	1/235 (0.4%)		1/233 (0.4%)
Thermal burn	1/235 (0.4%)		1/233 (0.4%)
Contusion	1/235 (0.4%)		0/233 (0%)
Incision site pain	0/235 (0%)		1/233 (0.4%)
Overdose	0/235 (0%)		1/233 (0.4%)
Radiation skin injury	1/235 (0.4%)		0/233 (0%)
Skin wound	1/235 (0.4%)		0/233 (0%)
Investigations
Weight decreased	18/235 (7.7%)		8/233 (3.4%)
Blood lactate dehydrogenase increased	3/235 (1.3%)		2/233 (0.9%)
Platelet count decreased	4/235 (1.7%)		1/233 (0.4%)
Haemoglobin decreased	3/235 (1.3%)		1/233 (0.4%)
Alanine aminotransferase increased	2/235 (0.9%)		1/233 (0.4%)
Weight increased	2/235 (0.9%)		1/233 (0.4%)
Blood glucose increased	0/235 (0%)		2/233 (0.9%)
Neutrophil count decreased	2/235 (0.9%)		0/233 (0%)
White blood cell count decreased	1/235 (0.4%)		1/233 (0.4%)
Aspartate aminotransferase increased	0/235 (0%)		1/233 (0.4%)
Bacterial test positive	1/235 (0.4%)		0/233 (0%)
Blood alkaline phosphatase increased	1/235 (0.4%)		0/233 (0%)
Blood bilirubin increased	0/235 (0%)		1/233 (0.4%)
Blood creatinine increased	0/235 (0%)		1/233 (0.4%)
Blood magnesium increased	1/235 (0.4%)		0/233 (0%)
Blood phosphorus decreased	0/235 (0%)		1/233 (0.4%)
Blood phosphorus increased	1/235 (0.4%)		0/233 (0%)
Blood urea increased	0/235 (0%)		1/233 (0.4%)
Blood uric acid increased	0/235 (0%)		1/233 (0.4%)
Body temperature increased	1/235 (0.4%)		0/233 (0%)
Breath sounds abnormal	0/235 (0%)		1/233 (0.4%)
Gamma-glutamyltransferase increased	0/235 (0%)		1/233 (0.4%)
International normalised ratio increased	1/235 (0.4%)		0/233 (0%)
Metabolism and nutrition disorders
Decreased appetite	28/235 (11.9%)		17/233 (7.3%)
Increased appetite	7/235 (3%)		6/233 (2.6%)
Hypokalaemia	9/235 (3.8%)		3/233 (1.3%)
Hyperglycaemia	4/235 (1.7%)		3/233 (1.3%)
Dehydration	2/235 (0.9%)		4/233 (1.7%)
Hyponatraemia	3/235 (1.3%)		1/233 (0.4%)
Cachexia	2/235 (0.9%)		1/233 (0.4%)
Hypoalbuminaemia	3/235 (1.3%)		0/233 (0%)
Hypomagnesaemia	1/235 (0.4%)		2/233 (0.9%)
Hypocalcaemia	1/235 (0.4%)		1/233 (0.4%)
Hyperkalaemia	1/235 (0.4%)		0/233 (0%)
Malnutrition	1/235 (0.4%)		0/233 (0%)
Polydipsia	1/235 (0.4%)		0/233 (0%)
Musculoskeletal and connective tissue disorders
Muscular weakness	29/235 (12.3%)		22/233 (9.4%)
Pain in extremity	8/235 (3.4%)		6/233 (2.6%)
Arthralgia	6/235 (2.6%)		6/233 (2.6%)
Back pain	4/235 (1.7%)		4/233 (1.7%)
Muscle spasms	4/235 (1.7%)		2/233 (0.9%)
Musculoskeletal pain	4/235 (1.7%)		1/233 (0.4%)
Myalgia	2/235 (0.9%)		2/233 (0.9%)
Joint swelling	0/235 (0%)		2/233 (0.9%)
Neck pain	2/235 (0.9%)		0/233 (0%)
Bone pain	1/235 (0.4%)		0/233 (0%)
Extremity contracture	1/235 (0.4%)		0/233 (0%)
Groin pain	0/235 (0%)		1/233 (0.4%)
Muscle atrophy	0/235 (0%)		1/233 (0.4%)
Musculoskeletal chest pain	1/235 (0.4%)		0/233 (0%)
Osteoarthritis	1/235 (0.4%)		0/233 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain	3/235 (1.3%)		3/233 (1.3%)
Tumour pain	2/235 (0.9%)		1/233 (0.4%)
Lung neoplasm malignant	1/235 (0.4%)		0/233 (0%)
Metastases to skin	1/235 (0.4%)		0/233 (0%)
Non-small cell lung cancer	1/235 (0.4%)		0/233 (0%)
Nervous system disorders
Headache	27/235 (11.5%)		28/233 (12%)
Dizziness	27/235 (11.5%)		19/233 (8.2%)
Somnolence	14/235 (6%)		14/233 (6%)
Hypoaesthesia	6/235 (2.6%)		11/233 (4.7%)
Ataxia	8/235 (3.4%)		6/233 (2.6%)
Coordination abnormal	7/235 (3%)		4/233 (1.7%)
Tremor	6/235 (2.6%)		4/233 (1.7%)
Paraesthesia	5/235 (2.1%)		4/233 (1.7%)
Amnesia	2/235 (0.9%)		6/233 (2.6%)
Dysgeusia	6/235 (2.6%)		2/233 (0.9%)
Aphasia	1/235 (0.4%)		6/233 (2.6%)
Balance disorder	0/235 (0%)		7/233 (3%)
Convulsion	4/235 (1.7%)		1/233 (0.4%)
Epilepsy	1/235 (0.4%)		3/233 (1.3%)
Neuropathy peripheral	2/235 (0.9%)		2/233 (0.9%)
Peripheral sensory neuropathy	2/235 (0.9%)		2/233 (0.9%)
Speech disorder	1/235 (0.4%)		3/233 (1.3%)
Syncope	2/235 (0.9%)		1/233 (0.4%)
Brain oedema	1/235 (0.4%)		1/233 (0.4%)
Convulsions local	2/235 (0.9%)		0/233 (0%)
Hemiparesis	0/235 (0%)		2/233 (0.9%)
Hemiplegia	1/235 (0.4%)		1/233 (0.4%)
Loss of consciousness	1/235 (0.4%)		1/233 (0.4%)
Memory impairment	1/235 (0.4%)		1/233 (0.4%)
Psychomotor hyperactivity	0/235 (0%)		2/233 (0.9%)
Ageusia	0/235 (0%)		1/233 (0.4%)
Alcoholic seizure	0/235 (0%)		1/233 (0.4%)
Burning sensation	1/235 (0.4%)		0/233 (0%)
Cognitive disorder	1/235 (0.4%)		0/233 (0%)
Dysarthria	0/235 (0%)		1/233 (0.4%)
Facial paresis	1/235 (0.4%)		0/233 (0%)
Hypersomnia	0/235 (0%)		1/233 (0.4%)
Hypotonia	1/235 (0.4%)		0/233 (0%)
Mental impairment	0/235 (0%)		1/233 (0.4%)
Monoplegia	1/235 (0.4%)		0/233 (0%)
Neuritis	0/235 (0%)		1/233 (0.4%)
Paresis	1/235 (0.4%)		0/233 (0%)
Partial seizures	1/235 (0.4%)		0/233 (0%)
Peripheral motor neuropathy	1/235 (0.4%)		0/233 (0%)
Polyneuropathy	0/235 (0%)		1/233 (0.4%)
Sciatica	0/235 (0%)		1/233 (0.4%)
Visual field defect	0/235 (0%)		1/233 (0.4%)
Psychiatric disorders
Insomnia	17/235 (7.2%)		19/233 (8.2%)
Confusional state	7/235 (3%)		11/233 (4.7%)
Anxiety	4/235 (1.7%)		1/233 (0.4%)
Depression	2/235 (0.9%)		2/233 (0.9%)
Mood altered	0/235 (0%)		2/233 (0.9%)
Nervousness	0/235 (0%)		2/233 (0.9%)
Delusion	0/235 (0%)		1/233 (0.4%)
Depressed mood	1/235 (0.4%)		0/233 (0%)
Disorientation	0/235 (0%)		1/233 (0.4%)
Initial insomnia	0/235 (0%)		1/233 (0.4%)
Mental disorder	1/235 (0.4%)		0/233 (0%)
Sleep disorder	0/235 (0%)		1/233 (0.4%)
Staring	0/235 (0%)		1/233 (0.4%)
Renal and urinary disorders
Haematuria	2/235 (0.9%)		1/233 (0.4%)
Dysuria	2/235 (0.9%)		0/233 (0%)
Pollakiuria	1/235 (0.4%)		1/233 (0.4%)
Chromaturia	0/235 (0%)		1/233 (0.4%)
Incontinence	0/235 (0%)		1/233 (0.4%)
Nephrolithiasis	1/235 (0.4%)		0/233 (0%)
Proteinuria	0/235 (0%)		1/233 (0.4%)
Urinary bladder haemorrhage	0/235 (0%)		1/233 (0.4%)
Urinary incontinence	1/235 (0.4%)		0/233 (0%)
Urinary retention	1/235 (0.4%)		0/233 (0%)
Reproductive system and breast disorders
Epididymitis	1/235 (0.4%)		0/233 (0%)
Prostatitis	1/235 (0.4%)		0/233 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	31/235 (13.2%)		20/233 (8.6%)
Cough	26/235 (11.1%)		17/233 (7.3%)
Epistaxis	8/235 (3.4%)		2/233 (0.9%)
Haemoptysis	3/235 (1.3%)		7/233 (3%)
Oropharyngeal pain	5/235 (2.1%)		3/233 (1.3%)
Hiccups	3/235 (1.3%)		2/233 (0.9%)
Dyspnoea exertional	1/235 (0.4%)		3/233 (1.3%)
Hypoxia	2/235 (0.9%)		1/233 (0.4%)
Productive cough	1/235 (0.4%)		2/233 (0.9%)
Dysphonia	1/235 (0.4%)		1/233 (0.4%)
Lung infiltration	0/235 (0%)		2/233 (0.9%)
Pleural effusion	1/235 (0.4%)		1/233 (0.4%)
Pulmonary embolism	2/235 (0.9%)		0/233 (0%)
Upper-airway cough syndrome	2/235 (0.9%)		0/233 (0%)
Wheezing	2/235 (0.9%)		0/233 (0%)
Bronchitis chronic	1/235 (0.4%)		0/233 (0%)
Chronic obstructive pulmonary disease	1/235 (0.4%)		0/233 (0%)
Hydrothorax	1/235 (0.4%)		0/233 (0%)
Increased upper airway secretion	1/235 (0.4%)		0/233 (0%)
Laryngeal inflammation	0/235 (0%)		1/233 (0.4%)
Pharyngeal inflammation	0/235 (0%)		1/233 (0.4%)
Pneumothorax	1/235 (0.4%)		0/233 (0%)
Pulmonary hypertension	0/235 (0%)		1/233 (0.4%)
Rales	0/235 (0%)		1/233 (0.4%)
Respiratory failure	1/235 (0.4%)		0/233 (0%)
Respiratory tract congestion	0/235 (0%)		1/233 (0.4%)
Rhinorrhoea	1/235 (0.4%)		0/233 (0%)
Skin and subcutaneous tissue disorders
Alopecia	21/235 (8.9%)		17/233 (7.3%)
Erythema	4/235 (1.7%)		1/233 (0.4%)
Pruritus	5/235 (2.1%)		0/233 (0%)
Rash	2/235 (0.9%)		3/233 (1.3%)
Dry skin	1/235 (0.4%)		2/233 (0.9%)
Swelling face	1/235 (0.4%)		2/233 (0.9%)
Acne	1/235 (0.4%)		1/233 (0.4%)
Ecchymosis	1/235 (0.4%)		1/233 (0.4%)
Night sweats	1/235 (0.4%)		1/233 (0.4%)
Skin disorder	0/235 (0%)		2/233 (0.9%)
Skin ulcer	1/235 (0.4%)		1/233 (0.4%)
Dermatitis allergic	0/235 (0%)		1/233 (0.4%)
Haemorrhage subcutaneous	1/235 (0.4%)		0/233 (0%)
Increased tendency to bruise	0/235 (0%)		1/233 (0.4%)
Petechiae	1/235 (0.4%)		0/233 (0%)
Rash papular	1/235 (0.4%)		0/233 (0%)
Skin exfoliation	0/235 (0%)		1/233 (0.4%)
Vascular disorders
Hypotension	6/235 (2.6%)		0/233 (0%)
Deep vein thrombosis	1/235 (0.4%)		2/233 (0.9%)
Hypertension	2/235 (0.9%)		1/233 (0.4%)
Flushing	1/235 (0.4%)		1/233 (0.4%)
Phlebitis	2/235 (0.9%)		0/233 (0%)
Haematoma	0/235 (0%)		1/233 (0.4%)
Hot flush	0/235 (0%)		1/233 (0.4%)
Orthostatic hypotension	0/235 (0%)		1/233 (0.4%)
Thrombophlebitis superficial	1/235 (0.4%)		0/233 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.