Temozolomide Alone or in Combination With Thalidomide and/or Isotretinoin and/or Celecoxib in Treating Patients Who Have Undergone Radiation Therapy for Glioblastoma Multiforme
Study Details
Study Description
Brief Summary
RATIONALE: Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Thalidomide may stop the growth of glioblastoma multiforme by blocking blood flow to the tumor. Isotretinoin may help cells that are involved in the body's immune response to work better. Celecoxib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known which temozolomide-containing regimen is more effective in treating glioblastoma multiforme.
PURPOSE: This randomized phase II trial is studying eight different temozolomide-containing regimens to compare how well they work in treating patients who have undergone radiation therapy for glioblastoma multiforme.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
Phase 2 |
Detailed Description
OBJECTIVES:
-
Compare the efficacy of adjuvant temozolomide (TMZ) alone or in combination with thalidomide and/or isotretinoin and/or celecoxib, in terms of 6-month progression-free survival, in patients who have undergone radiotherapy for supratentorial glioblastoma multiforme.
-
Compare the toxicity of these regimens in these patients.
OUTLINE: This is a randomized, multicenter study. Patients are randomized to 1 of 8 treatment arms.
-
Arm I: Patients receive oral temozolomide once daily on days 1-7 and 15-21.
-
Arm II: Patients receive temozolomide as in arm I and oral thalidomide once daily on days 1-28.
-
Arm III: Patients receive temozolomide as in arm I and oral isotretinoin twice daily on days 1-21.
-
Arm IV: Patients receive temozolomide as in arm I and oral celecoxib twice daily on days 1-28.
-
Arm V: Patients receive temozolomide as in arm I, thalidomide as in arm II, and isotretinoin as in arm III.
-
Arm VI: Patients receive temozolomide as in arm I, thalidomide as in arm II, and celecoxib as in arm IV.
-
Arm VII: Patients receive temozolomide as in arm I, isotretinoin as in arm III, and celecoxib as in arm IV.
-
Arm VIII: Patients receive temozolomide as in arm I, thalidomide as in arm II, isotretinoin as in arm III, and celecoxib as in arm IV.
In all arms, treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Patient may receive additional courses of therapy at the discretion of the treating physician.
After completion of study treatment, patients are followed for at least 30 days and then every 3 months thereafter.
PROJECTED ACCRUAL: A total of 180 patients will be accrued for this study.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Active Comparator: Arm I: TMZ Oral Temozolomide (TMZ) 150 mg/m^2 once daily on days 1-7 and 15-21. |
Drug: Temozolomide
150 mg/m2 orally daily, 7 days on treatment, 7 days off.
Other Names:
|
Experimental: Arm II: TMZ + Thalidomide Temozolomide as in arm I and oral Thalidomide (Thal) once daily on days 1-28 (starting dose 200 mg). |
Drug: Temozolomide
150 mg/m2 orally daily, 7 days on treatment, 7 days off.
Other Names:
Drug: Thalidomide
400 mg orally every day continuous dosing (starting at 200 mg each day and escalating weekly by 100 mg until the maximum dose of 400 mg/day is achieved)
Other Names:
|
Experimental: Arm III: TMZ + Isotretinoin Temozolomide as in Arm I and oral Isotretinoin 40 mg/m^2 twice daily on days 1-21. |
Drug: Isotretinoin
40 mg/m^2 orally twice a day (total daily dose = 80 mg/m^2) days 1-21 of a 28 day cycle.
Other Names:
Drug: Temozolomide
150 mg/m2 orally daily, 7 days on treatment, 7 days off.
Other Names:
|
Experimental: Arm IV: TMZ + Celecoxib Temozolomide as in arm I and oral Celecoxib 400 mg twice daily on days 1-28. |
Drug: Celecoxib
400 mg orally twice a day continuous dosing
Other Names:
Drug: Temozolomide
150 mg/m2 orally daily, 7 days on treatment, 7 days off.
Other Names:
|
Experimental: Arm V: TMZ + Thalidomide + Isotretinoin Temozolomide as in arm I, Thalidomide as in arm II, and Isotretinoin as in arm III. |
Drug: Isotretinoin
40 mg/m^2 orally twice a day (total daily dose = 80 mg/m^2) days 1-21 of a 28 day cycle.
Other Names:
Drug: Temozolomide
150 mg/m2 orally daily, 7 days on treatment, 7 days off.
Other Names:
Drug: Thalidomide
400 mg orally every day continuous dosing (starting at 200 mg each day and escalating weekly by 100 mg until the maximum dose of 400 mg/day is achieved)
Other Names:
|
Experimental: Arm VI: TMZ + Thalidomide + Celecoxib Temozolomide as in Arm I, Thalidomide as in Arm II, and Celecoxib as in Arm IV. |
Drug: Celecoxib
400 mg orally twice a day continuous dosing
Other Names:
Drug: Temozolomide
150 mg/m2 orally daily, 7 days on treatment, 7 days off.
Other Names:
Drug: Thalidomide
400 mg orally every day continuous dosing (starting at 200 mg each day and escalating weekly by 100 mg until the maximum dose of 400 mg/day is achieved)
Other Names:
|
Experimental: Arm VII: TMZ + Isotretinoin + Celecoxib Temozolomide as in Arm I, Isotretinoin as in Arm III, and Celecoxib as in Arm IV. |
Drug: Celecoxib
400 mg orally twice a day continuous dosing
Other Names:
Drug: Isotretinoin
40 mg/m^2 orally twice a day (total daily dose = 80 mg/m^2) days 1-21 of a 28 day cycle.
Other Names:
Drug: Temozolomide
150 mg/m2 orally daily, 7 days on treatment, 7 days off.
Other Names:
|
Experimental: Arm VIII: TMZ + Thalidomide + Isotretinoin + Celecoxib Temozolomide as in Arm I, Thalidomide as in Arm II, Isotretinoin as in Arm III, and Celecoxib as in Arm IV. |
Drug: Celecoxib
400 mg orally twice a day continuous dosing
Other Names:
Drug: Isotretinoin
40 mg/m^2 orally twice a day (total daily dose = 80 mg/m^2) days 1-21 of a 28 day cycle.
Other Names:
Drug: Temozolomide
150 mg/m2 orally daily, 7 days on treatment, 7 days off.
Other Names:
Drug: Thalidomide
400 mg orally every day continuous dosing (starting at 200 mg each day and escalating weekly by 100 mg until the maximum dose of 400 mg/day is achieved)
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Median Progression-Free Survival (PFS) Comparison of Thalidomide Arms Versus no Thalidomide Arms [Every 2 cycles (1 cycle = 28 days) from randomization until progression of disease, death or last follow-up, up to one year (12 study cycles).]
Thalidomide versus not Thalidomide analysis: Comparison of median PFS outcome of participants in arms II, VI, VII and VIII, versus participants in arms I, III, IV and V. Median PFS was estimated using the Kaplan-Meier method from time of randomization to time of progression, death, or last follow-up. Progression defined as 25% increase in the sum of products of all measurable lesions over smallest sum observed (over baseline if no decrease) using the same techniques as baseline, OR clear worsening of any evaluable disease, OR appearance of any new lesion/site, OR failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer).
- Median Progression-Free Survival (PFS) Comparison of Celecoxib Arms Versus no Celecoxib Arms [Every 2 cycles (1 cycle = 28 days) from randomization until progression of disease, death or last follow-up.]
Celecoxib versus not Celecoxib analysis: We compared the median PFS outcome of participants in arms III, V, VI and VIII, versus participants in arms I, II, IV and VII. Median PFS was estimated using the Kaplan-Meier method from time of randomization to time of progression, death, or last follow-up. Progression defined as 25% increase in the sum of products of all measurable lesions over smallest sum observed (over baseline if no decrease) using the same techniques as baseline, OR clear worsening of any evaluable disease, OR appearance of any new lesion/site, OR failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer).
- Median Progression-Free Survival (PFS) Comparison of Isotretinoin Arms Versus no Isotretinoin Arms [Every 2 cycles (1 cycle = 28 days) from randomization until progression of disease, death or last follow-up.]
Isotretinoin versus not Isotretinoin analysis: We compared the median PFS outcome of participants in arms IV, V, VII and VIII, versus participants in arms I, II, III and VI. Median PFS was estimated using the Kaplan-Meier method from time of randomization to time of progression, death, or last follow-up. Progression defined as 25% increase in the sum of products of all measurable lesions over smallest sum observed (over baseline if no decrease) using the same techniques as baseline, OR clear worsening of any evaluable disease, OR appearance of any new lesion/site, OR failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer).
Secondary Outcome Measures
- Median Progression-Free Survival (PFS) Comparison of Doublet Versus Triplet Therapy [Every 2 cycles (1 cycle = 28 days) from randomization until progression of disease, death or last follow-up.]
Doublet (2 agents) versus Triplet (3 agents) therapy analysis: We compared the median PFS outcome of participants in arms II, III, IV, versus participants in arms V, VI and VII. Median PFS was estimated using the Kaplan-Meier method from time of randomization to time of progression, death, or last follow-up. Progression defined as 25% increase in the sum of products of all measurable lesions over smallest sum observed (over baseline if no decrease) using the same techniques as baseline, OR clear worsening of any evaluable disease, OR appearance of any new lesion/site, OR failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer).
- Median Progression-Free Survival (PFS) of Individual Arms [Every 2 cycles (1 cycle = 28 days) from randomization until progression of disease, death or last follow-up.]
Median PFS was estimated using the Kaplan-Meier method from time of randomization to time of progression, death, or last follow-up. Progression defined as 25% increase in the sum of products of all measurable lesions over smallest sum observed (over baseline if no decrease) using the same techniques as baseline, OR clear worsening of any evaluable disease, OR appearance of any new lesion/site, OR failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer).
- Median Overall Survival (OS) Comparison of Thalidomide Arms Versus no Thalidomide Arms [Every 3 months from randomization until progression of disease, death or last follow-up.]
Thalidomide versus not Thalidomide analysis: We compared the median OS outcome of participants in arms II, VI, VII and VIII, versus participants in arms I, III, IV and V. Median OS was estimated using the Kaplan-Meier method from time of randomization to time of progression, death, or last follow-up. Progression defined as 25% increase in the sum of products of all measurable lesions over smallest sum observed (over baseline if no decrease) using the same techniques as baseline, OR clear worsening of any evaluable disease, OR appearance of any new lesion/site, OR failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer).
- Median Overall Survival (OS) Comparison of Celecoxib Arms Versus no Celecoxib Arms [Every 3 months from randomization until progression of disease, death or last follow-up.]
Celecoxib versus not Celecoxib analysis: We compared the median OS outcome of participants in arms III, V, VI and VIII, versus participants in arms I, II, IV and VII. Median OS was estimated using the Kaplan-Meier method from time of randomization to time of progression, death, or last follow-up. Progression defined as 25% increase in the sum of products of all measurable lesions over smallest sum observed (over baseline if no decrease) using the same techniques as baseline, OR clear worsening of any evaluable disease, OR appearance of any new lesion/site, OR failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer).
- Median Overall Survival (OS) Comparison of Isotretinoin Arms Versus no Isotretinoin Arms [Every 3 months from randomization until progression of disease, death or last follow-up.]
Isotretinoin versus not Isotretinoin analysis: We compared the median OS outcome of participants in arms IV, V, VII and VIII, versus participants in arms I, II, III and VI. Median OS was estimated using the Kaplan-Meier method from time of randomization to time of progression, death, or last follow-up. Progression defined as 25% increase in the sum of products of all measurable lesions over smallest sum observed (over baseline if no decrease) using the same techniques as baseline, OR clear worsening of any evaluable disease, OR appearance of any new lesion/site, OR failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer).
- Median Overall Survival (OS) Comparison of Doublet Versus Triplet Therapy [Every 3 months from randomization until progression of disease, death or last follow-up.]
Doublet (2 agents) versus Triplet (3 agents) therapy analysis: We compared the median OS outcome of participants in arms II, III, IV, versus participants in arms V, VI and VII. Median OS was estimated using the Kaplan-Meier method from time of randomization to time of progression, death, or last follow-up. Progression defined as 25% increase in the sum of products of all measurable lesions over smallest sum observed (over baseline if no decrease) using the same techniques as baseline, OR clear worsening of any evaluable disease, OR appearance of any new lesion/site, OR failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer).
- Overall Survival of Individual Arms [Every 3 months from randomization until progression of disease, death or last follow-up.]
Overall Survival (OS) was estimated using the Kaplan-Meier method from time of randomization to time of progression, death, or last follow-up. Progression defined as 25% increase in the sum of products of all measurable lesions over smallest sum observed (over baseline if no decrease) using the same techniques as baseline, OR clear worsening of any evaluable disease, OR appearance of any new lesion/site, OR failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer).
Eligibility Criteria
Criteria
DISEASE CHARACTERISTICS:
-
Histologically confirmed supratentorial glioblastoma multiforme
-
Must have undergone a biopsy OR subtotal or gross total resection of the tumor
-
Must have completed post-operative (or post-biopsy) radiotherapy within the past 5 weeks
-
No progressive disease after radiotherapy
PATIENT CHARACTERISTICS:
Age
- 18 and over
Performance status
- Karnofsky 60-100%
Life expectancy
- Not specified
Hematopoietic
-
Absolute neutrophil count ≥ 1,500/mm^3
-
Platelet count ≥ 100,000/mm^3
Hepatic
-
Serum glutamate pyruvate transaminase (SGPT) < 2 times upper limit of normal (ULN)
-
Alkaline phosphatase < 2 times ULN
-
Bilirubin ≤ 1.5 mg/dL
Renal
-
blood urea nitrogen (BUN) ≤ 1.5 times ULN
-
Creatinine ≤ 1.5 times ULN
Immunologic
-
No history of allergic reactions attributed to compounds of similar chemical or biological composition to celecoxib or to sulfonamides
-
No asthma, urticaria, or allergic reactions to aspirin or other NSAIDs
-
No active infection
Gastrointestinal
-
No inflammatory bowel disease
-
No history of peptic ulcer disease
-
No gastrointestinal bleeding within past 3 months
Other
-
Not pregnant or nursing
-
Negative pregnancy test
-
Fertile patients must use effective double-method contraception during and for 2 months after study participation
-
Fertile female patients randomized to receive thalidomide must use effective double-method contraception for ≥ 4 weeks before, during, and ≥ 4 weeks after completion of study therapy
-
Fertile male patients randomized to receive thalidomide must use effective contraception during and for ≥ 4 weeks after completion of study therapy
-
No blood donation (for patients randomized to receive thalidomide)
-
No history of any other cancer except nonmelanoma skin cancer or carcinoma in situ of the cervix or cancer that is in complete remission and patient completed all therapy for that disease ≥ 3 years ago
-
No other disease that would obscure toxicity or dangerously alter drug metabolism (e.g., severe connective tissue disease)
-
No other serious medical illness
PRIOR CONCURRENT THERAPY:
Biologic therapy
- Not specified
Chemotherapy
-
Prior temozolomide in combination with radiotherapy allowed
-
No other prior or concurrent chemotherapy
Endocrine therapy
- Not specified
Radiotherapy
-
See Disease Characteristics
-
See Chemotherapy
Surgery
-
See Disease Characteristics
-
No concurrent surgery
Other
-
No other concurrent non-steroidal anti-inflammatory drugs (NSAIDs) (for patients randomized to receive celecoxib)
-
No other concurrent investigational drugs
-
No other concurrent anticancer therapy
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Hembree Mercy Cancer Center at St. Edward Mercy Medical Center | Fort Smith | Arkansas | United States | 72913 |
2 | University of Texas MD Anderson Cancer Center at Orlando | Orlando | Florida | United States | 32806-2134 |
3 | CCOP - Atlanta Regional | Atlanta | Georgia | United States | 30342-1701 |
4 | CCOP - Central Illinois | Decatur | Illinois | United States | 62526 |
5 | CCOP - Wichita | Wichita | Kansas | United States | 67214-3882 |
6 | CCOP - Grand Rapids | Grand Rapids | Michigan | United States | 49503 |
7 | CCOP - Kalamazoo | Kalamazoo | Michigan | United States | 49007-3731 |
8 | CCOP - Kansas City | Kansas City | Missouri | United States | 64131 |
9 | Cancer Research for the Ozarks | Springfield | Missouri | United States | 65804 |
10 | Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center | Columbus | Ohio | United States | 43210-1240 |
11 | CCOP - Upstate Carolina | Spartanburg | South Carolina | United States | 29303 |
12 | University of Texas MD Anderson Cancer Center | Houston | Texas | United States | 77030-4009 |
Sponsors and Collaborators
- M.D. Anderson Cancer Center
- National Cancer Institute (NCI)
Investigators
- Study Chair: Marta Penas-Prado, MD, M.D. Anderson Cancer Center
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- 2004-0662
- MDA-ID-02586
- NCI-6636
- MDA-2004-0662
- CDR0000432954
- NCI-2009-00076
Study Results
Participant Flow
Recruitment Details | Recruitment Period: September 2005 to February 2011 from various hospitals and institutions representing the Community Clinical Oncology Program (CCOP). A total of 146 participants were accrued at MD Anderson Cancer Center and 32 at the remaining participating sites. |
---|---|
Pre-assignment Detail |
Arm/Group Title | Arm I: TMZ | Arm II: TMZ + Thalidomide | Arm III: TMZ + Celecoxib | Arm IV: TMZ + Isotretinoin | Arm V: TMZ + Isotretinoin + Celecoxib | Arm VI: TMZ + Thalidomide + Celecoxib | Arm VII: TMZ + Thalidomide + Isotretinoin | Arm VIII: TMZ + Thalidomide + Isotretinoin + Celecoxib |
---|---|---|---|---|---|---|---|---|
Arm/Group Description | Oral Temozolomide (TMZ): 150 mg/m^2 once daily on days 1-7 and 15-21. | Oral Temozolomide (TMZ): 150 mg/m^2 once daily on days 1-7 and 15-21. Thalidomide: 400 mg orally every day continuous dosing (starting at 200 mg each day and escalating weekly by 100 mg until the maximum dose of 400 mg/day is achieved). | Oral Temozolomide (TMZ): 150 mg/m^2 once daily on days 1-7 and 15-21. Celecoxib: 400 mg orally twice a day continuous dosing. | Oral Temozolomide (TMZ): 150 mg/m^2 once daily on days 1-7 and 15-21. Isotretinoin: 40 mg/m^2 orally twice a day (total daily dose = 80 mg/m^2) days 1-21 of a 28 day cycle. | Oral Temozolomide (TMZ): 150 mg/m^2 once daily on days 1-7 and 15-21. Celecoxib: 400 mg orally twice a day continuous dosing. Isotretinoin: 40 mg/m^2 orally twice a day (total daily dose = 80 mg/m^2) days 1-21 of a 28 day cycle. | Oral Temozolomide (TMZ): 150 mg/m^2 once daily on days 1-7 and 15-21. Celecoxib: 400 mg orally twice a day continuous dosing. Thalidomide: 400 mg orally every day continuous dosing (starting at 200 mg each day and escalating weekly by 100 mg until the maximum dose of 400 mg/day is achieved). | Oral Temozolomide (TMZ): 150 mg/m^2 once daily on days 1-7 and 15-21. Isotretinoin: 40 mg/m^2 orally twice a day (total daily dose = 80 mg/m^2) days 1-21 of a 28 day cycle. Thalidomide: 400 mg orally every day continuous dosing (starting at 200 mg each day and escalating weekly by 100 mg until the maximum dose of 400 mg/day is achieved). | Oral Temozolomide (TMZ): 150 mg/m^2 once daily on days 1-7 and 15-21. Celecoxib: 400 mg orally twice a day continuous dosing. Isotretinoin: 40 mg/m^2 orally twice a day (total daily dose = 80 mg/m^2) days 1-21 of a 28 day cycle. Thalidomide: 400 mg orally every day continuous dosing (starting at 200 mg each day and escalating weekly by 100 mg until the maximum dose of 400 mg/day is achieved). |
Period Title: Overall Study | ||||||||
STARTED | 22 | 22 | 22 | 22 | 23 | 22 | 23 | 22 |
COMPLETED | 22 | 21 | 21 | 18 | 21 | 17 | 20 | 15 |
NOT COMPLETED | 0 | 1 | 1 | 4 | 2 | 5 | 3 | 7 |
Baseline Characteristics
Arm/Group Title | Arm I: TMZ | Arm II: TMZ + Thalidomide | Arm III: TMZ + Celecoxib | Arm IV: TMZ + Isotretinoin | Arm V: TMZ + Isotretinoin + Celecoxib | Arm VI: TMZ + Thalidomide + Celecoxib | Arm VII: TMZ + Thalidomide + Isotretinoin | Arm VIII: TMZ + Thalidomide + Isotretinoin + Celecoxib | Total |
---|---|---|---|---|---|---|---|---|---|
Arm/Group Description | Oral Temozolomide (TMZ): 150 mg/m^2 once daily on days 1-7 and 15-21. | Oral Temozolomide (TMZ): 150 mg/m^2 once daily on days 1-7 and 15-21. Thalidomide: 400 mg orally every day continuous dosing (starting at 200 mg each day and escalating weekly by 100 mg until the maximum dose of 400 mg/day is achieved). | Oral Temozolomide (TMZ): 150 mg/m^2 once daily on days 1-7 and 15-21. Celecoxib: 400 mg orally twice a day continuous dosing. | Oral Temozolomide (TMZ): 150 mg/m^2 once daily on days 1-7 and 15-21. Isotretinoin: 40 mg/m^2 orally twice a day (total daily dose = 80 mg/m^2) days 1-21 of a 28 day cycle. | Oral Temozolomide (TMZ): 150 mg/m^2 once daily on days 1-7 and 15-21. Celecoxib: 400 mg orally twice a day continuous dosing. Isotretinoin: 40 mg/m^2 orally twice a day (total daily dose = 80 mg/m^2) days 1-21 of a 28 day cycle. | Oral Temozolomide (TMZ): 150 mg/m^2 once daily on days 1-7 and 15-21. Celecoxib: 400 mg orally twice a day continuous dosing. Thalidomide: 400 mg orally every day continuous dosing (starting at 200 mg each day and escalating weekly by 100 mg until the maximum dose of 400 mg/day is achieved). | Oral Temozolomide (TMZ): 150 mg/m^2 once daily on days 1-7 and 15-21. Isotretinoin: 40 mg/m^2 orally twice a day (total daily dose = 80 mg/m^2) days 1-21 of a 28 day cycle. Thalidomide: 400 mg orally every day continuous dosing (starting at 200 mg each day and escalating weekly by 100 mg until the maximum dose of 400 mg/day is achieved). | Oral Temozolomide (TMZ): 150 mg/m^2 once daily on days 1-7 and 15-21. Celecoxib: 400 mg orally twice a day continuous dosing. Isotretinoin: 40 mg/m^2 orally twice a day (total daily dose = 80 mg/m^2) days 1-21 of a 28 day cycle. Thalidomide: 400 mg orally every day continuous dosing (starting at 200 mg each day and escalating weekly by 100 mg until the maximum dose of 400 mg/day is achieved). | Total of all reporting groups |
Overall Participants | 22 | 22 | 22 | 22 | 23 | 22 | 23 | 22 | 178 |
Age, Customized (participants) [Number] | |||||||||
<=19 years: |
0
0%
|
0
0%
|
0
0%
|
1
4.5%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
0.6%
|
Between 20 and 59 years: |
17
77.3%
|
12
54.5%
|
17
77.3%
|
14
63.6%
|
20
87%
|
18
81.8%
|
15
65.2%
|
17
77.3%
|
130
73%
|
>=60 years: |
5
22.7%
|
10
45.5%
|
5
22.7%
|
7
31.8%
|
3
13%
|
4
18.2%
|
8
34.8%
|
5
22.7%
|
47
26.4%
|
Sex: Female, Male (Count of Participants) | |||||||||
Female |
7
31.8%
|
10
45.5%
|
5
22.7%
|
8
36.4%
|
4
17.4%
|
6
27.3%
|
6
26.1%
|
9
40.9%
|
55
30.9%
|
Male |
15
68.2%
|
12
54.5%
|
17
77.3%
|
14
63.6%
|
19
82.6%
|
16
72.7%
|
17
73.9%
|
13
59.1%
|
123
69.1%
|
Region of Enrollment (participants) [Number] | |||||||||
United States |
22
100%
|
22
100%
|
22
100%
|
22
100%
|
23
100%
|
22
100%
|
23
100%
|
22
100%
|
178
100%
|
Outcome Measures
Title | Median Progression-Free Survival (PFS) Comparison of Thalidomide Arms Versus no Thalidomide Arms |
---|---|
Description | Thalidomide versus not Thalidomide analysis: Comparison of median PFS outcome of participants in arms II, VI, VII and VIII, versus participants in arms I, III, IV and V. Median PFS was estimated using the Kaplan-Meier method from time of randomization to time of progression, death, or last follow-up. Progression defined as 25% increase in the sum of products of all measurable lesions over smallest sum observed (over baseline if no decrease) using the same techniques as baseline, OR clear worsening of any evaluable disease, OR appearance of any new lesion/site, OR failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer). |
Time Frame | Every 2 cycles (1 cycle = 28 days) from randomization until progression of disease, death or last follow-up, up to one year (12 study cycles). |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Thalidomide: Arm II, Arm VI, Arm VII and Arm VIII | No Thalidomide: Arm I, Arm III, Arm IV and Arm V |
---|---|---|
Arm/Group Description | Arm II: TMZ + Thalidomide, Arm VI: TMZ + Thalidomide + Celecoxib, Arm VII: TMZ + Thalidomide + Isotretinoin and Arm VIII: TMZ + Thalidomide + Isotretinoin + Celecoxib Thalidomide: 400 mg orally every day continuous dosing (starting at 200 mg each day and escalating weekly by 100 mg until the maximum dose of 400 mg/day is achieved). Oral Temozolomide (TMZ): 150 mg/m^2 once daily on days 1-7 and 15-21. Celecoxib: 400 mg orally twice a day continuous dosing. Isotretinoin: 40 mg/m^2 orally twice a day (total daily dose = 80 mg/m^2) days 1-21 of a 28 day cycle. | Arm I: TMZ, Arm III: TMZ + Celecoxib, Arm IV: TMZ + Isotretinoin and Arm V: TMZ + Isotretinoin + Celecoxib Oral Temozolomide (TMZ): 150 mg/m^2 once daily on days 1-7 and 15-21. Celecoxib: 400 mg orally twice a day continuous dosing. Isotretinoin: 40 mg/m^2 orally twice a day (total daily dose = 80 mg/m^2) days 1-21 of a 28 day cycle. |
Measure Participants | 70 | 85 |
Median (95% Confidence Interval) [months] |
7.6
|
8.7
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Thalidomide: Arm II, Arm VI, Arm VII and Arm VIII, No Thalidomide: Arm I, Arm III, Arm IV and Arm V |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority or Other (legacy) | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
Estimated Value | 1.2 | |
Confidence Interval |
(2-Sided) 95% 0.8 to 1.7 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Median Progression-Free Survival (PFS) Comparison of Celecoxib Arms Versus no Celecoxib Arms |
---|---|
Description | Celecoxib versus not Celecoxib analysis: We compared the median PFS outcome of participants in arms III, V, VI and VIII, versus participants in arms I, II, IV and VII. Median PFS was estimated using the Kaplan-Meier method from time of randomization to time of progression, death, or last follow-up. Progression defined as 25% increase in the sum of products of all measurable lesions over smallest sum observed (over baseline if no decrease) using the same techniques as baseline, OR clear worsening of any evaluable disease, OR appearance of any new lesion/site, OR failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer). |
Time Frame | Every 2 cycles (1 cycle = 28 days) from randomization until progression of disease, death or last follow-up. |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Celecoxib: Arm III, Arm V, Arm VI and Arm VIII | No Celecoxib: Arm I, Arm II, Arm IV and Arm VII |
---|---|---|
Arm/Group Description | Arm III: TMZ + Celecoxib, Arm V: TMZ + Isotretinoin + Celecoxib, Arm VI: TMZ + Thalidomide + Celecoxib and Arm VIII: TMZ + Thalidomide + Isotretinoin + Celecoxib Thalidomide: 400 mg orally every day continuous dosing (starting at 200 mg each day and escalating weekly by 100 mg until the maximum dose of 400 mg/day is achieved). Oral Temozolomide (TMZ): 150 mg/m^2 once daily on days 1-7 and 15-21. Celecoxib: 400 mg orally twice a day continuous dosing. Isotretinoin: 40 mg/m^2 orally twice a day (total daily dose = 80 mg/m^2) days 1-21 of a 28 day cycle. | Arm I: TMZ, Arm II: TMZ + Thalidomide, Arm IV: TMZ + Isotretinoin and Arm VII: TMZ + Thalidomide + Isotretinoin. Thalidomide: 400 mg orally every day continuous dosing (starting at 200 mg each day and escalating weekly by 100 mg until the maximum dose of 400 mg/day is achieved). Oral Temozolomide (TMZ): 150 mg/m^2 once daily on days 1-7 and 15-21. Isotretinoin: 40 mg/m^2 orally twice a day (total daily dose = 80 mg/m^2) days 1-21 of a 28 day cycle. |
Measure Participants | 74 | 81 |
Median (95% Confidence Interval) [months] |
8.3
|
7.4
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Thalidomide: Arm II, Arm VI, Arm VII and Arm VIII, No Thalidomide: Arm I, Arm III, Arm IV and Arm V |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority or Other (legacy) | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
Estimated Value | 0.8 | |
Confidence Interval |
(2-Sided) 95% 0.6 to 1.2 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Median Progression-Free Survival (PFS) Comparison of Isotretinoin Arms Versus no Isotretinoin Arms |
---|---|
Description | Isotretinoin versus not Isotretinoin analysis: We compared the median PFS outcome of participants in arms IV, V, VII and VIII, versus participants in arms I, II, III and VI. Median PFS was estimated using the Kaplan-Meier method from time of randomization to time of progression, death, or last follow-up. Progression defined as 25% increase in the sum of products of all measurable lesions over smallest sum observed (over baseline if no decrease) using the same techniques as baseline, OR clear worsening of any evaluable disease, OR appearance of any new lesion/site, OR failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer). |
Time Frame | Every 2 cycles (1 cycle = 28 days) from randomization until progression of disease, death or last follow-up. |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Isotretinoin: Arm IV, Arm V, Arm VII and Arm VIII | No Isotretinoin: Arm I, Arm II, Arm III and Arm VI |
---|---|---|
Arm/Group Description | Arm IV: TMZ + Isotretinoin, Arm V: TMZ + Isotretinoin + Celecoxib, Arm VII: TMZ + Thalidomide + Isotretinoin and Arm VIII: TMZ + Thalidomide + Isotretinoin + Celecoxib Thalidomide: 400 mg orally every day continuous dosing (starting at 200 mg each day and escalating weekly by 100 mg until the maximum dose of 400 mg/day is achieved). Oral Temozolomide (TMZ): 150 mg/m^2 once daily on days 1-7 and 15-21. Celecoxib: 400 mg orally twice a day continuous dosing. Isotretinoin: 40 mg/m^2 orally twice a day (total daily dose = 80 mg/m^2) days 1-21 of a 28 day cycle. | Arm I: TMZ, Arm II: TMZ + Thalidomide, Arm III: TMZ + Celecoxib and Arm VI: TMZ + Thalidomide + Celecoxib Thalidomide: 400 mg orally every day continuous dosing (starting at 200 mg each day and escalating weekly by 100 mg until the maximum dose of 400 mg/day is achieved). Oral Temozolomide (TMZ): 150 mg/m^2 once daily on days 1-7 and 15-21. Celecoxib: 400 mg orally twice a day continuous dosing. |
Measure Participants | 74 | 81 |
Median (95% Confidence Interval) [months] |
6.6
|
9.1
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Thalidomide: Arm II, Arm VI, Arm VII and Arm VIII, No Thalidomide: Arm I, Arm III, Arm IV and Arm V |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority or Other (legacy) | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
Estimated Value | 1.3 | |
Confidence Interval |
(2-Sided) 95% 0.9 to 1.8 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Median Progression-Free Survival (PFS) Comparison of Doublet Versus Triplet Therapy |
---|---|
Description | Doublet (2 agents) versus Triplet (3 agents) therapy analysis: We compared the median PFS outcome of participants in arms II, III, IV, versus participants in arms V, VI and VII. Median PFS was estimated using the Kaplan-Meier method from time of randomization to time of progression, death, or last follow-up. Progression defined as 25% increase in the sum of products of all measurable lesions over smallest sum observed (over baseline if no decrease) using the same techniques as baseline, OR clear worsening of any evaluable disease, OR appearance of any new lesion/site, OR failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer). |
Time Frame | Every 2 cycles (1 cycle = 28 days) from randomization until progression of disease, death or last follow-up. |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Doublet (2 Agents): Arm II, Arm III and Arm IV | Triplet (3 Agents): Arm V, Arm VI and Arm VII |
---|---|---|
Arm/Group Description | Arm II: TMZ + Thalidomide, Arm III: TMZ + Celecoxib and Arm IV: TMZ + Isotretinoin Oral Temozolomide (TMZ): 150 mg/m^2 once daily on days 1-7 and 15-21. Thalidomide: 400 mg orally every day continuous dosing (starting at 200 mg each day and escalating weekly by 100 mg until the maximum dose of 400 mg/day is achieved). Celecoxib: 400 mg orally twice a day continuous dosing. Isotretinoin: 40 mg/m^2 orally twice a day (total daily dose = 80 mg/m^2) days 1-21 of a 28 day cycle. | Arm V: TMZ + Isotretinoin + Celecoxib, Arm VI: TMZ + Thalidomide + Celecoxib and Arm VII: Thalidomide + Celecoxib + Isotretinoin Oral Temozolomide (TMZ): 150 mg/m^2 once daily on days 1-7 and 15-21. Thalidomide: 400 mg orally every day continuous dosing (starting at 200 mg each day and escalating weekly by 100 mg until the maximum dose of 400 mg/day is achieved). Celecoxib: 400 mg orally twice a day continuous dosing. Isotretinoin: 40 mg/m^2 orally twice a day (total daily dose = 80 mg/m^2) days 1-21 of a 28 day cycle. |
Measure Participants | 60 | 58 |
Median (95% Confidence Interval) [months] |
8.3
|
8.2
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Thalidomide: Arm II, Arm VI, Arm VII and Arm VIII, No Thalidomide: Arm I, Arm III, Arm IV and Arm V |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority or Other (legacy) | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
Estimated Value | 0.9 | |
Confidence Interval |
(2-Sided) 95% 0.6 to 1.3 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Median Progression-Free Survival (PFS) of Individual Arms |
---|---|
Description | Median PFS was estimated using the Kaplan-Meier method from time of randomization to time of progression, death, or last follow-up. Progression defined as 25% increase in the sum of products of all measurable lesions over smallest sum observed (over baseline if no decrease) using the same techniques as baseline, OR clear worsening of any evaluable disease, OR appearance of any new lesion/site, OR failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer). |
Time Frame | Every 2 cycles (1 cycle = 28 days) from randomization until progression of disease, death or last follow-up. |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Arm I: TMZ | Arm II: TMZ + Thalidomide | Arm III: TMZ + Celecoxib | Arm IV: TMZ + Isotretinoin | Arm V: TMZ + Isotretinoin + Celecoxib | Arm VI: TMZ + Thalidomide + Celecoxib | Arm VII: TMZ + Thalidomide + Isotretinoin | Arm VIII: TMZ + Thalidomide + Isotretinoin + Celecoxib |
---|---|---|---|---|---|---|---|---|
Arm/Group Description | Oral Temozolomide (TMZ): 150 mg/m^2 once daily on days 1-7 and 15-21. | Oral Temozolomide (TMZ): 150 mg/m^2 once daily on days 1-7 and 15-21. Thalidomide: 400 mg orally every day continuous dosing (starting at 200 mg each day and escalating weekly by 100 mg until the maximum dose of 400 mg/day is achieved). | Oral Temozolomide (TMZ): 150 mg/m^2 once daily on days 1-7 and 15-21. Celecoxib: 400 mg orally twice a day continuous dosing. | Oral Temozolomide (TMZ): 150 mg/m^2 once daily on days 1-7 and 15-21. Isotretinoin: 40 mg/m^2 orally twice a day (total daily dose = 80 mg/m^2) days 1-21 of a 28 day cycle. | Oral Temozolomide (TMZ): 150 mg/m^2 once daily on days 1-7 and 15-21. Celecoxib: 400 mg orally twice a day continuous dosing. Isotretinoin: 40 mg/m^2 orally twice a day (total daily dose = 80 mg/m^2) days 1-21 of a 28 day cycle. | Oral Temozolomide (TMZ): 150 mg/m^2 once daily on days 1-7 and 15-21. Celecoxib: 400 mg orally twice a day continuous dosing. Thalidomide: 400 mg orally every day continuous dosing (starting at 200 mg each day and escalating weekly by 100 mg until the maximum dose of 400 mg/day is achieved). | Oral Temozolomide (TMZ): 150 mg/m^2 once daily on days 1-7 and 15-21. Isotretinoin: 40 mg/m^2 orally twice a day (total daily dose = 80 mg/m^2) days 1-21 of a 28 day cycle. Thalidomide: 400 mg orally every day continuous dosing (starting at 200 mg each day and escalating weekly by 100 mg until the maximum dose of 400 mg/day is achieved). | Oral Temozolomide (TMZ): 150 mg/m^2 once daily on days 1-7 and 15-21. Celecoxib: 400 mg orally twice a day continuous dosing. Isotretinoin: 40 mg/m^2 orally twice a day (total daily dose = 80 mg/m^2) days 1-21 of a 28 day cycle. Thalidomide: 400 mg orally every day continuous dosing (starting at 200 mg each day and escalating weekly by 100 mg until the maximum dose of 400 mg/day is achieved). |
Measure Participants | 22 | 18 | 21 | 21 | 21 | 20 | 17 | 15 |
Median (95% Confidence Interval) [months] |
10.5
|
7.7
|
13.4
|
6.5
|
11.6
|
7.9
|
6.2
|
5.8
|
Title | Median Overall Survival (OS) Comparison of Thalidomide Arms Versus no Thalidomide Arms |
---|---|
Description | Thalidomide versus not Thalidomide analysis: We compared the median OS outcome of participants in arms II, VI, VII and VIII, versus participants in arms I, III, IV and V. Median OS was estimated using the Kaplan-Meier method from time of randomization to time of progression, death, or last follow-up. Progression defined as 25% increase in the sum of products of all measurable lesions over smallest sum observed (over baseline if no decrease) using the same techniques as baseline, OR clear worsening of any evaluable disease, OR appearance of any new lesion/site, OR failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer). |
Time Frame | Every 3 months from randomization until progression of disease, death or last follow-up. |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Thalidomide: Arm II, Arm VI, Arm VII and Arm VIII | No Thalidomide: Arm I, Arm III, Arm IV and Arm V |
---|---|---|
Arm/Group Description | Arm II: TMZ + Thalidomide, Arm VI: TMZ + Thalidomide + Celecoxib, Arm VII: TMZ + Thalidomide + Isotretinoin and Arm VIII: TMZ + Thalidomide + Isotretinoin + Celecoxib Thalidomide: 400 mg orally every day continuous dosing (starting at 200 mg each day and escalating weekly by 100 mg until the maximum dose of 400 mg/day is achieved). Oral Temozolomide (TMZ): 150 mg/m^2 once daily on days 1-7 and 15-21. Celecoxib: 400 mg orally twice a day continuous dosing. Isotretinoin: 40 mg/m^2 orally twice a day (total daily dose = 80 mg/m^2) days 1-21 of a 28 day cycle. | Arm I: TMZ, Arm III: TMZ + Celecoxib, Arm IV: TMZ + Isotretinoin and Arm V: TMZ + Isotretinoin + Celecoxib Oral Temozolomide (TMZ): 150 mg/m^2 once daily on days 1-7 and 15-21. Celecoxib: 400 mg orally twice a day continuous dosing. Isotretinoin: 40 mg/m^2 orally twice a day (total daily dose = 80 mg/m^2) days 1-21 of a 28 day cycle. |
Measure Participants | 70 | 85 |
Median (95% Confidence Interval) [months] |
18.3
|
17.4
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Thalidomide: Arm II, Arm VI, Arm VII and Arm VIII, No Thalidomide: Arm I, Arm III, Arm IV and Arm V |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority or Other (legacy) | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
Estimated Value | 1.0 | |
Confidence Interval |
(2-Sided) 95% 0.7 to 1.5 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Median Overall Survival (OS) Comparison of Celecoxib Arms Versus no Celecoxib Arms |
---|---|
Description | Celecoxib versus not Celecoxib analysis: We compared the median OS outcome of participants in arms III, V, VI and VIII, versus participants in arms I, II, IV and VII. Median OS was estimated using the Kaplan-Meier method from time of randomization to time of progression, death, or last follow-up. Progression defined as 25% increase in the sum of products of all measurable lesions over smallest sum observed (over baseline if no decrease) using the same techniques as baseline, OR clear worsening of any evaluable disease, OR appearance of any new lesion/site, OR failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer). |
Time Frame | Every 3 months from randomization until progression of disease, death or last follow-up. |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Celecoxib: Arm III, Arm V, Arm VI and Arm VIII | No Celecoxib: Arm I, Arm II, Arm IV and Arm VII |
---|---|---|
Arm/Group Description | Arm III: TMZ + Celecoxib, Arm V: TMZ + Isotretinoin + Celecoxib, Arm VI: TMZ + Thalidomide + Celecoxib and Arm VIII: TMZ + Thalidomide + Isotretinoin + Celecoxib Thalidomide: 400 mg orally every day continuous dosing (starting at 200 mg each day and escalating weekly by 100 mg until the maximum dose of 400 mg/day is achieved). Oral Temozolomide (TMZ): 150 mg/m^2 once daily on days 1-7 and 15-21. Celecoxib: 400 mg orally twice a day continuous dosing. Isotretinoin: 40 mg/m^2 orally twice a day (total daily dose = 80 mg/m^2) days 1-21 of a 28 day cycle. | Arm I: TMZ, Arm II: TMZ + Thalidomide, Arm IV: TMZ + Isotretinoin and Arm VII: TMZ + Thalidomide + Isotretinoin. Thalidomide: 400 mg orally every day continuous dosing (starting at 200 mg each day and escalating weekly by 100 mg until the maximum dose of 400 mg/day is achieved). Oral Temozolomide (TMZ): 150 mg/m^2 once daily on days 1-7 and 15-21. Isotretinoin: 40 mg/m^2 orally twice a day (total daily dose = 80 mg/m^2) days 1-21 of a 28 day cycle. |
Measure Participants | 74 | 81 |
Median (95% Confidence Interval) [months] |
20.2
|
17.1
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Thalidomide: Arm II, Arm VI, Arm VII and Arm VIII, No Thalidomide: Arm I, Arm III, Arm IV and Arm V |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority or Other (legacy) | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
Estimated Value | 0.8 | |
Confidence Interval |
(2-Sided) 95% 0.5 to 1.2 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Median Overall Survival (OS) Comparison of Isotretinoin Arms Versus no Isotretinoin Arms |
---|---|
Description | Isotretinoin versus not Isotretinoin analysis: We compared the median OS outcome of participants in arms IV, V, VII and VIII, versus participants in arms I, II, III and VI. Median OS was estimated using the Kaplan-Meier method from time of randomization to time of progression, death, or last follow-up. Progression defined as 25% increase in the sum of products of all measurable lesions over smallest sum observed (over baseline if no decrease) using the same techniques as baseline, OR clear worsening of any evaluable disease, OR appearance of any new lesion/site, OR failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer). |
Time Frame | Every 3 months from randomization until progression of disease, death or last follow-up. |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Isotretinoin: Arm IV, Arm V, Arm VII and ARM VIII | No Isotretinoin: Arm I, Arm II, Arm III and ARM VI |
---|---|---|
Arm/Group Description | Arm IV: TMZ + Isotretinoin, Arm V: TMZ + Isotretinoin + Celecoxib, Arm VII: TMZ + Thalidomide + Isotretinoin and Arm VIII: TMZ + Thalidomide + Isotretinoin + Celecoxib Thalidomide: 400 mg orally every day continuous dosing (starting at 200 mg each day and escalating weekly by 100 mg until the maximum dose of 400 mg/day is achieved). Oral Temozolomide (TMZ): 150 mg/m^2 once daily on days 1-7 and 15-21. Celecoxib: 400 mg orally twice a day continuous dosing. Isotretinoin: 40 mg/m^2 orally twice a day (total daily dose = 80 mg/m^2) days 1-21 of a 28 day cycle. | Arm I: TMZ, Arm II: TMZ + Thalidomide, Arm III: TMZ + Celecoxib and Arm VI: TMZ + Thalidomide + Celecoxib Thalidomide: 400 mg orally every day continuous dosing (starting at 200 mg each day and escalating weekly by 100 mg until the maximum dose of 400 mg/day is achieved). Oral Temozolomide (TMZ): 150 mg/m^2 once daily on days 1-7 and 15-21. Celecoxib: 400 mg orally twice a day continuous dosing. |
Measure Participants | 74 | 81 |
Median (95% Confidence Interval) [months] |
17.1
|
19.9
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Thalidomide: Arm II, Arm VI, Arm VII and Arm VIII, No Thalidomide: Arm I, Arm III, Arm IV and Arm V |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority or Other (legacy) | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
Estimated Value | 1.2 | |
Confidence Interval |
(2-Sided) 95% 0.8 to 1.8 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Median Overall Survival (OS) Comparison of Doublet Versus Triplet Therapy |
---|---|
Description | Doublet (2 agents) versus Triplet (3 agents) therapy analysis: We compared the median OS outcome of participants in arms II, III, IV, versus participants in arms V, VI and VII. Median OS was estimated using the Kaplan-Meier method from time of randomization to time of progression, death, or last follow-up. Progression defined as 25% increase in the sum of products of all measurable lesions over smallest sum observed (over baseline if no decrease) using the same techniques as baseline, OR clear worsening of any evaluable disease, OR appearance of any new lesion/site, OR failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer). |
Time Frame | Every 3 months from randomization until progression of disease, death or last follow-up. |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Doublet (2 Agents): Arm II, Arm III and Arm IV | Triplet (3 Agents): Arm V, Arm VI and Arm VII |
---|---|---|
Arm/Group Description | Arm II: TMZ + Thalidomide, Arm III: TMZ + Celecoxib and Arm IV: TMZ + Isotretinoin Oral Temozolomide (TMZ): 150 mg/m^2 once daily on days 1-7 and 15-21. Thalidomide: 400 mg orally every day continuous dosing (starting at 200 mg each day and escalating weekly by 100 mg until the maximum dose of 400 mg/day is achieved). Celecoxib: 400 mg orally twice a day continuous dosing. Isotretinoin: 40 mg/m^2 orally twice a day (total daily dose = 80 mg/m^2) days 1-21 of a 28 day cycle. | Arm V: TMZ + Isotretinoin + Celecoxib, Arm VI: TMZ + Thalidomide + Celecoxib and Arm VII: Thalidomide + Celecoxib + Isotretinoin Oral Temozolomide (TMZ): 150 mg/m^2 once daily on days 1-7 and 15-21. Thalidomide: 400 mg orally every day continuous dosing (starting at 200 mg each day and escalating weekly by 100 mg until the maximum dose of 400 mg/day is achieved). Celecoxib: 400 mg orally twice a day continuous dosing. Isotretinoin: 40 mg/m^2 orally twice a day (total daily dose = 80 mg/m^2) days 1-21 of a 28 day cycle. |
Measure Participants | 60 | 58 |
Median (95% Confidence Interval) [months] |
17.0
|
20.1
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Thalidomide: Arm II, Arm VI, Arm VII and Arm VIII, No Thalidomide: Arm I, Arm III, Arm IV and Arm V |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority or Other (legacy) | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
Estimated Value | 0.7 | |
Confidence Interval |
(2-Sided) 95% 0.5 to 1.1 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Overall Survival of Individual Arms |
---|---|
Description | Overall Survival (OS) was estimated using the Kaplan-Meier method from time of randomization to time of progression, death, or last follow-up. Progression defined as 25% increase in the sum of products of all measurable lesions over smallest sum observed (over baseline if no decrease) using the same techniques as baseline, OR clear worsening of any evaluable disease, OR appearance of any new lesion/site, OR failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer). |
Time Frame | Every 3 months from randomization until progression of disease, death or last follow-up. |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Arm I: TMZ | Arm II: TMZ + Thalidomide | Arm III: TMZ + Celecoxib | Arm IV: TMZ + Isotretinoin | Arm V: TMZ + Isotretinoin + Celecoxib | Arm VI: TMZ + Thalidomide + Celecoxib | Arm VII: TMZ + Thalidomide + Isotretinoin | Arm VIII: TMZ + Thalidomide + Isotretinoin + Celecoxib |
---|---|---|---|---|---|---|---|---|
Arm/Group Description | Oral Temozolomide (TMZ): 150 mg/m^2 once daily on days 1-7 and 15-21. | Oral Temozolomide (TMZ): 150 mg/m^2 once daily on days 1-7 and 15-21. Thalidomide: 400 mg orally every day continuous dosing (starting at 200 mg each day and escalating weekly by 100 mg until the maximum dose of 400 mg/day is achieved). | Oral Temozolomide (TMZ): 150 mg/m^2 once daily on days 1-7 and 15-21. Celecoxib: 400 mg orally twice a day continuous dosing. | Oral Temozolomide (TMZ): 150 mg/m^2 once daily on days 1-7 and 15-21. Isotretinoin: 40 mg/m^2 orally twice a day (total daily dose = 80 mg/m^2) days 1-21 of a 28 day cycle. | Oral Temozolomide (TMZ): 150 mg/m^2 once daily on days 1-7 and 15-21. Celecoxib: 400 mg orally twice a day continuous dosing. Isotretinoin: 40 mg/m^2 orally twice a day (total daily dose = 80 mg/m^2) days 1-21 of a 28 day cycle. | Oral Temozolomide (TMZ): 150 mg/m^2 once daily on days 1-7 and 15-21. Celecoxib: 400 mg orally twice a day continuous dosing. Thalidomide: 400 mg orally every day continuous dosing (starting at 200 mg each day and escalating weekly by 100 mg until the maximum dose of 400 mg/day is achieved). | Oral Temozolomide (TMZ): 150 mg/m^2 once daily on days 1-7 and 15-21. Isotretinoin: 40 mg/m^2 orally twice a day (total daily dose = 80 mg/m^2) days 1-21 of a 28 day cycle. Thalidomide: 400 mg orally every day continuous dosing (starting at 200 mg each day and escalating weekly by 100 mg until the maximum dose of 400 mg/day is achieved). | Oral Temozolomide (TMZ): 150 mg/m^2 once daily on days 1-7 and 15-21. Celecoxib: 400 mg orally twice a day continuous dosing. Isotretinoin: 40 mg/m^2 orally twice a day (total daily dose = 80 mg/m^2) days 1-21 of a 28 day cycle. Thalidomide: 400 mg orally every day continuous dosing (starting at 200 mg each day and escalating weekly by 100 mg until the maximum dose of 400 mg/day is achieved). |
Measure Participants | 22 | 18 | 21 | 21 | 21 | 20 | 17 | 15 |
Median (95% Confidence Interval) [months] |
21.2
|
17.4
|
18.1
|
11.7
|
23.1
|
20.2
|
17.9
|
18.5
|
Adverse Events
Time Frame | Adverse Events (AEs) and Serious Adverse Events (SAEs) were collected from study drug administration to time of progression, death, or last follow-up,1 year", "Adverse Events (AEs) and Serious Adverse Events (SAEs) were collected from study drug administration to time of progression, death, or last follow-up, up to 5 years. | |||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Adverse Event Reporting Description | ||||||||||||||||
Arm/Group Title | Arm I: TMZ | Arm II: TMZ + Thalidomide | Arm III: TMZ + Celecoxib | Arm IV: TMZ + Isotretinoin | Arm V: TMZ + Isotretinoin + Celecoxib | Arm VI: TMZ + Thalidomide + Celecoxib | Arm VII: TMZ + Thalidomide + Isotretinoin | Arm VIII: TMZ + Thalidomide + Isotretinoin + Celecoxib | ||||||||
Arm/Group Description | Oral Temozolomide (TMZ): 150 mg/m^2 once daily on days 1-7 and 15-21. | Oral Temozolomide (TMZ): 150 mg/m^2 once daily on days 1-7 and 15-21. Thalidomide: 400 mg orally every day continuous dosing (starting at 200 mg each day and escalating weekly by 100 mg until the maximum dose of 400 mg/day is achieved). | Oral Temozolomide (TMZ): 150 mg/m^2 once daily on days 1-7 and 15-21. Celecoxib: 400 mg orally twice a day continuous dosing. | Oral Temozolomide (TMZ): 150 mg/m^2 once daily on days 1-7 and 15-21. Isotretinoin: 40 mg/m^2 orally twice a day (total daily dose = 80 mg/m^2) days 1-21 of a 28 day cycle. | Oral Temozolomide (TMZ): 150 mg/m^2 once daily on days 1-7 and 15-21. Celecoxib: 400 mg orally twice a day continuous dosing. Isotretinoin: 40 mg/m^2 orally twice a day (total daily dose = 80 mg/m^2) days 1-21 of a 28 day cycle. | Oral Temozolomide (TMZ): 150 mg/m^2 once daily on days 1-7 and 15-21. Celecoxib: 400 mg orally twice a day continuous dosing. Thalidomide: 400 mg orally every day continuous dosing (starting at 200 mg each day and escalating weekly by 100 mg until the maximum dose of 400 mg/day is achieved). | Oral Temozolomide (TMZ): 150 mg/m^2 once daily on days 1-7 and 15-21. Isotretinoin: 40 mg/m^2 orally twice a day (total daily dose = 80 mg/m^2) days 1-21 of a 28 day cycle. Thalidomide: 400 mg orally every day continuous dosing (starting at 200 mg each day and escalating weekly by 100 mg until the maximum dose of 400 mg/day is achieved). | Oral Temozolomide (TMZ): 150 mg/m^2 once daily on days 1-7 and 15-21. Celecoxib: 400 mg orally twice a day continuous dosing. Isotretinoin: 40 mg/m^2 orally twice a day (total daily dose = 80 mg/m^2) days 1-21 of a 28 day cycle. Thalidomide: 400 mg orally every day continuous dosing (starting at 200 mg each day and escalating weekly by 100 mg until the maximum dose of 400 mg/day is achieved). | ||||||||
All Cause Mortality |
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Arm I: TMZ | Arm II: TMZ + Thalidomide | Arm III: TMZ + Celecoxib | Arm IV: TMZ + Isotretinoin | Arm V: TMZ + Isotretinoin + Celecoxib | Arm VI: TMZ + Thalidomide + Celecoxib | Arm VII: TMZ + Thalidomide + Isotretinoin | Arm VIII: TMZ + Thalidomide + Isotretinoin + Celecoxib | |||||||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||||||
Serious Adverse Events |
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Arm I: TMZ | Arm II: TMZ + Thalidomide | Arm III: TMZ + Celecoxib | Arm IV: TMZ + Isotretinoin | Arm V: TMZ + Isotretinoin + Celecoxib | Arm VI: TMZ + Thalidomide + Celecoxib | Arm VII: TMZ + Thalidomide + Isotretinoin | Arm VIII: TMZ + Thalidomide + Isotretinoin + Celecoxib | |||||||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 11/22 (50%) | 9/21 (42.9%) | 7/21 (33.3%) | 8/18 (44.4%) | 12/21 (57.1%) | 15/17 (88.2%) | 8/20 (40%) | 7/15 (46.7%) | ||||||||
Blood and lymphatic system disorders | ||||||||||||||||
Lymphopenia | 10/22 (45.5%) | 10 | 5/21 (23.8%) | 5 | 5/21 (23.8%) | 5 | 5/18 (27.8%) | 5 | 11/21 (52.4%) | 11 | 10/17 (58.8%) | 10 | 3/20 (15%) | 3 | 4/15 (26.7%) | 4 |
Platelets | 1/22 (4.5%) | 1 | 1/21 (4.8%) | 1 | 1/21 (4.8%) | 1 | 1/18 (5.6%) | 1 | 0/21 (0%) | 0 | 2/17 (11.8%) | 2 | 1/20 (5%) | 1 | 0/15 (0%) | 0 |
Leukocytes | 0/22 (0%) | 0 | 2/21 (9.5%) | 2 | 0/21 (0%) | 0 | 2/18 (11.1%) | 2 | 0/21 (0%) | 0 | 1/17 (5.9%) | 1 | 2/20 (10%) | 2 | 0/15 (0%) | 0 |
Neutrophils | 0/22 (0%) | 0 | 3/21 (14.3%) | 3 | 0/21 (0%) | 0 | 2/18 (11.1%) | 2 | 0/21 (0%) | 0 | 2/17 (11.8%) | 2 | 3/20 (15%) | 3 | 1/15 (6.7%) | 1 |
Hemoglobin | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 1/21 (4.8%) | 1 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Thrombocytopenia | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 1/21 (4.8%) | 1 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Cardiac disorders | ||||||||||||||||
Sinus Bradycardia | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 1/17 (5.9%) | 1 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
General disorders | ||||||||||||||||
Death | 0/22 (0%) | 0 | 1/21 (4.8%) | 1 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 1/17 (5.9%) | 1 | 1/20 (5%) | 1 | 0/15 (0%) | 0 |
Fatigue | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 1/21 (4.8%) | 1 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Obesity | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 1/21 (4.8%) | 1 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 1/15 (6.7%) | 1 |
Metabolism and nutrition disorders | ||||||||||||||||
Hyperkalemia | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 1/21 (4.8%) | 1 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Hyperglycemia | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 1/18 (5.6%) | 1 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Musculoskeletal and connective tissue disorders | ||||||||||||||||
Gait/Walking | 0/22 (0%) | 0 | 1/21 (4.8%) | 1 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||||||
Lymphoma | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 1/18 (5.6%) | 1 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Nervous system disorders | ||||||||||||||||
Pyramidal Tract Dysfunction | 0/22 (0%) | 0 | 1/21 (4.8%) | 1 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Respiratory, thoracic and mediastinal disorders | ||||||||||||||||
Pneumonia | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 1/21 (4.8%) | 1 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Dyspnea | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 1/20 (5%) | 1 | 1/15 (6.7%) | 1 |
Skin and subcutaneous tissue disorders | ||||||||||||||||
Erythema Multiforme | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 1/15 (6.7%) | 1 |
Vascular disorders | ||||||||||||||||
Thrombosis | 1/22 (4.5%) | 1 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 1/18 (5.6%) | 1 | 0/21 (0%) | 0 | 1/17 (5.9%) | 1 | 2/20 (10%) | 2 | 1/15 (6.7%) | 1 |
Pulmonary Embolism | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 1/17 (5.9%) | 1 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
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Arm I: TMZ | Arm II: TMZ + Thalidomide | Arm III: TMZ + Celecoxib | Arm IV: TMZ + Isotretinoin | Arm V: TMZ + Isotretinoin + Celecoxib | Arm VI: TMZ + Thalidomide + Celecoxib | Arm VII: TMZ + Thalidomide + Isotretinoin | Arm VIII: TMZ + Thalidomide + Isotretinoin + Celecoxib | |||||||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 22/22 (100%) | 21/21 (100%) | 21/21 (100%) | 18/18 (100%) | 21/21 (100%) | 17/17 (100%) | 20/20 (100%) | 15/15 (100%) | ||||||||
Blood and lymphatic system disorders | ||||||||||||||||
Leukocytes | 16/22 (72.7%) | 54 | 14/21 (66.7%) | 28 | 16/21 (76.2%) | 43 | 15/18 (83.3%) | 34 | 16/21 (76.2%) | 66 | 17/17 (100%) | 35 | 11/20 (55%) | 36 | 14/15 (93.3%) | 32 |
Lymphopenia | 22/22 (100%) | 99 | 21/21 (100%) | 35 | 21/21 (100%) | 70 | 18/18 (100%) | 50 | 21/21 (100%) | 74 | 17/17 (100%) | 69 | 12/20 (60%) | 23 | 12/15 (80%) | 17 |
Neutrophils | 13/22 (59.1%) | 37 | 11/21 (52.4%) | 25 | 9/21 (42.9%) | 30 | 10/18 (55.6%) | 21 | 11/21 (52.4%) | 19 | 17/17 (100%) | 24 | 7/20 (35%) | 27 | 12/15 (80%) | 22 |
Platelets | 13/22 (59.1%) | 35 | 5/21 (23.8%) | 8 | 12/21 (57.1%) | 28 | 13/18 (72.2%) | 17 | 11/21 (52.4%) | 31 | 14/17 (82.4%) | 26 | 9/20 (45%) | 22 | 11/15 (73.3%) | 14 |
Hemoglobin | 16/22 (72.7%) | 39 | 8/21 (38.1%) | 12 | 17/21 (81%) | 39 | 14/18 (77.8%) | 31 | 15/21 (71.4%) | 39 | 17/17 (100%) | 45 | 9/20 (45%) | 25 | 11/15 (73.3%) | 26 |
Anemia | 1/22 (4.5%) | 1 | 0/21 (0%) | 0 | 2/21 (9.5%) | 3 | 0/18 (0%) | 0 | 1/21 (4.8%) | 1 | 1/17 (5.9%) | 1 | 0/20 (0%) | 0 | 2/15 (13.3%) | 4 |
Hematocrit | 1/22 (4.5%) | 1 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
CO2 Serum High | 4/22 (18.2%) | 5 | 2/21 (9.5%) | 2 | 5/21 (23.8%) | 6 | 1/18 (5.6%) | 1 | 2/21 (9.5%) | 2 | 4/17 (23.5%) | 7 | 4/20 (20%) | 4 | 2/15 (13.3%) | 2 |
Edema | 4/22 (18.2%) | 4 | 2/21 (9.5%) | 2 | 6/21 (28.6%) | 6 | 2/18 (11.1%) | 2 | 3/21 (14.3%) | 4 | 6/17 (35.3%) | 9 | 3/20 (15%) | 4 | 6/15 (40%) | 6 |
Leukocytosis | 1/22 (4.5%) | 1 | 0/21 (0%) | 0 | 2/21 (9.5%) | 3 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
High Lactate Dehydrogenase | 8/22 (36.4%) | 10 | 3/21 (14.3%) | 3 | 4/21 (19%) | 5 | 5/18 (27.8%) | 7 | 3/21 (14.3%) | 3 | 3/17 (17.6%) | 4 | 2/20 (10%) | 2 | 3/15 (20%) | 4 |
High BUN Serum | 5/22 (22.7%) | 9 | 2/21 (9.5%) | 2 | 8/21 (38.1%) | 13 | 4/18 (22.2%) | 6 | 6/21 (28.6%) | 8 | 2/17 (11.8%) | 2 | 2/20 (10%) | 2 | 1/15 (6.7%) | 1 |
Edema | 1/22 (4.5%) | 1 | 0/21 (0%) | 0 | 1/21 (4.8%) | 1 | 1/18 (5.6%) | 1 | 0/21 (0%) | 0 | 1/17 (5.9%) | 1 | 1/20 (5%) | 1 | 1/15 (6.7%) | 1 |
Edema | 0/22 (0%) | 0 | 1/21 (4.8%) | 1 | 3/21 (14.3%) | 3 | 0/18 (0%) | 0 | 2/21 (9.5%) | 2 | 1/17 (5.9%) | 1 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Thrombotic Thrombocytopenic Purpura | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 1/21 (4.8%) | 1 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Low BUN Serum | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 1/18 (5.6%) | 1 | 1/21 (4.8%) | 1 | 2/17 (11.8%) | 2 | 1/20 (5%) | 1 | 1/15 (6.7%) | 1 |
Bilateral Ankle Swelling | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 1/18 (5.6%) | 1 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Low Lactate Dehydrogenase | 0/22 (0%) | 0 | 1/21 (4.8%) | 2 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 1/21 (4.8%) | 1 | 2/17 (11.8%) | 4 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Partial Thromboplastin Time | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 1/17 (5.9%) | 1 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Cardiac disorders | ||||||||||||||||
Sinus Bradycardia | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 1/17 (5.9%) | 1 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Supraventricular Arrhythmia-Sinus Tachycardia | 1/22 (4.5%) | 1 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Hypertension | 4/22 (18.2%) | 6 | 4/21 (19%) | 4 | 1/21 (4.8%) | 2 | 4/18 (22.2%) | 4 | 2/21 (9.5%) | 2 | 1/17 (5.9%) | 1 | 4/20 (20%) | 5 | 2/15 (13.3%) | 2 |
Hypotension | 1/22 (4.5%) | 1 | 1/21 (4.8%) | 1 | 2/21 (9.5%) | 2 | 2/18 (11.1%) | 2 | 0/21 (0%) | 0 | 2/17 (11.8%) | 2 | 1/20 (5%) | 1 | 0/15 (0%) | 0 |
Palpitations | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 2/18 (11.1%) | 2 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 1/20 (5%) | 1 | 0/15 (0%) | 0 |
Supraventricular Arrhythmia-Atrial Fibrillation | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 1/18 (5.6%) | 1 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Chest Tightness | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 1/17 (5.9%) | 1 | 1/20 (5%) | 1 | 0/15 (0%) | 0 |
Cardiac Arrhythmia | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 2/20 (10%) | 2 | 0/15 (0%) | 0 |
Ear and labyrinth disorders | ||||||||||||||||
Hearing Loss | 1/22 (4.5%) | 1 | 1/21 (4.8%) | 1 | 5/21 (23.8%) | 5 | 3/18 (16.7%) | 3 | 1/21 (4.8%) | 1 | 3/17 (17.6%) | 3 | 3/20 (15%) | 3 | 2/15 (13.3%) | 2 |
Left Ear Drainage | 1/22 (4.5%) | 1 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Otitis | 1/22 (4.5%) | 1 | 1/21 (4.8%) | 1 | 0/21 (0%) | 0 | 2/18 (11.1%) | 2 | 2/21 (9.5%) | 3 | 1/17 (5.9%) | 1 | 1/20 (5%) | 1 | 0/15 (0%) | 0 |
Ear Pain | 4/22 (18.2%) | 5 | 1/21 (4.8%) | 1 | 1/21 (4.8%) | 1 | 1/18 (5.6%) | 1 | 1/21 (4.8%) | 1 | 2/17 (11.8%) | 2 | 1/20 (5%) | 1 | 0/15 (0%) | 0 |
Tinnitus | 1/22 (4.5%) | 1 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 3/18 (16.7%) | 3 | 2/21 (9.5%) | 2 | 2/17 (11.8%) | 2 | 1/20 (5%) | 1 | 1/15 (6.7%) | 1 |
Ear Wax | 0/22 (0%) | 0 | 1/21 (4.8%) | 1 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Tympanic Membrane Perforation | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 1/17 (5.9%) | 1 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Otosclerosis | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 1/20 (5%) | 1 | 0/15 (0%) | 0 |
Endocrine disorders | ||||||||||||||||
Hot Flashes | 1/22 (4.5%) | 1 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Cushingoid | 0/22 (0%) | 0 | 1/21 (4.8%) | 1 | 1/21 (4.8%) | 1 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 1/20 (5%) | 1 | 0/15 (0%) | 0 |
Diabetes | 0/22 (0%) | 0 | 1/21 (4.8%) | 1 | 1/21 (4.8%) | 1 | 1/18 (5.6%) | 1 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 1/20 (5%) | 1 | 0/15 (0%) | 0 |
Hypothyroidism | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 1/18 (5.6%) | 1 | 0/21 (0%) | 0 | 1/17 (5.9%) | 1 | 2/20 (10%) | 2 | 1/15 (6.7%) | 1 |
Low Testosterone | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 1/17 (5.9%) | 1 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Thyroid Problems | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 1/15 (6.7%) | 1 |
Eye disorders | ||||||||||||||||
Blurred Vision | 4/22 (18.2%) | 6 | 1/21 (4.8%) | 1 | 4/21 (19%) | 4 | 2/18 (11.1%) | 2 | 4/21 (19%) | 4 | 4/17 (23.5%) | 4 | 3/20 (15%) | 4 | 4/15 (26.7%) | 4 |
Anopsia | 2/22 (9.1%) | 2 | 2/21 (9.5%) | 2 | 3/21 (14.3%) | 3 | 2/18 (11.1%) | 2 | 3/21 (14.3%) | 3 | 4/17 (23.5%) | 4 | 3/20 (15%) | 4 | 6/15 (40%) | 6 |
Lowered Visual Acuity | 1/22 (4.5%) | 1 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 1/18 (5.6%) | 1 | 2/21 (9.5%) | 2 | 1/17 (5.9%) | 1 | 1/20 (5%) | 1 | 0/15 (0%) | 0 |
Loss of Vision | 2/22 (9.1%) | 2 | 0/21 (0%) | 0 | 2/21 (9.5%) | 2 | 2/18 (11.1%) | 2 | 1/21 (4.8%) | 1 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Photophobia | 1/22 (4.5%) | 1 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 1/18 (5.6%) | 1 | 0/21 (0%) | 0 | 2/17 (11.8%) | 2 | 0/20 (0%) | 0 | 1/15 (6.7%) | 1 |
Retinopathy | 1/22 (4.5%) | 1 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Watery Eye | 1/22 (4.5%) | 1 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 1/18 (5.6%) | 1 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Diplopia | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 2/21 (9.5%) | 2 | 2/18 (11.1%) | 2 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 3/20 (15%) | 4 | 0/15 (0%) | 0 |
Dry Eye | 0/22 (0%) | 0 | 2/21 (9.5%) | 2 | 1/21 (4.8%) | 1 | 2/18 (11.1%) | 2 | 1/21 (4.8%) | 1 | 0/17 (0%) | 0 | 2/20 (10%) | 2 | 1/15 (6.7%) | 1 |
Eyelid Dysfunction | 0/22 (0%) | 0 | 1/21 (4.8%) | 1 | 1/21 (4.8%) | 1 | 0/18 (0%) | 0 | 2/21 (9.5%) | 2 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Nystagmus | 0/22 (0%) | 0 | 1/21 (4.8%) | 1 | 1/21 (4.8%) | 1 | 0/18 (0%) | 0 | 1/21 (4.8%) | 1 | 0/17 (0%) | 0 | 1/20 (5%) | 2 | 1/15 (6.7%) | 1 |
Extraocular Movement | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 1/21 (4.8%) | 1 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 1/20 (5%) | 1 | 0/15 (0%) | 0 |
Exophoria | 0/22 (0%) | 0 | 1/21 (4.8%) | 1 | 0/21 (0%) | 0 | 1/18 (5.6%) | 1 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 1/20 (5%) | 1 | 0/15 (0%) | 0 |
Esotropia | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 1/18 (5.6%) | 1 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 1/20 (5%) | 1 | 0/15 (0%) | 0 |
Astigmatism | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 1/21 (4.8%) | 1 | 0/17 (0%) | 0 | 1/20 (5%) | 1 | 0/15 (0%) | 0 |
Conjunctival Infection | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 2/21 (9.5%) | 2 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Eye Pain | 0/22 (0%) | 0 | 1/21 (4.8%) | 1 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 1/21 (4.8%) | 1 | 0/17 (0%) | 0 | 2/20 (10%) | 2 | 1/15 (6.7%) | 1 |
Photosensitivity | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 1/21 (4.8%) | 1 | 0/17 (0%) | 0 | 1/20 (5%) | 1 | 0/15 (0%) | 0 |
Asymmetrical Optic Cup | 0/22 (0%) | 0 | 1/21 (4.8%) | 1 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Anisocoria | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 1/17 (5.9%) | 1 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Swollen Eyes | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 1/20 (5%) | 1 | 1/15 (6.7%) | 1 |
Gastrointestinal disorders | ||||||||||||||||
Anorexia | 8/22 (36.4%) | 9 | 2/21 (9.5%) | 2 | 3/21 (14.3%) | 3 | 7/18 (38.9%) | 10 | 3/21 (14.3%) | 3 | 9/17 (52.9%) | 10 | 4/20 (20%) | 4 | 3/15 (20%) | 3 |
Constipation | 13/22 (59.1%) | 13 | 11/21 (52.4%) | 11 | 9/21 (42.9%) | 9 | 11/18 (61.1%) | 12 | 8/21 (38.1%) | 8 | 12/17 (70.6%) | 14 | 10/20 (50%) | 10 | 8/15 (53.3%) | 8 |
Colitis | 1/22 (4.5%) | 1 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Diarrhea | 1/22 (4.5%) | 1 | 0/21 (0%) | 0 | 3/21 (14.3%) | 5 | 4/18 (22.2%) | 4 | 1/21 (4.8%) | 1 | 4/17 (23.5%) | 4 | 5/20 (25%) | 6 | 3/15 (20%) | 3 |
Xerostomia | 1/22 (4.5%) | 1 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 1/20 (5%) | 1 | 0/15 (0%) | 0 |
Dysphagia | 2/22 (9.1%) | 2 | 1/21 (4.8%) | 1 | 1/21 (4.8%) | 1 | 2/18 (11.1%) | 2 | 1/21 (4.8%) | 1 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Bloating | 1/22 (4.5%) | 1 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 1/20 (5%) | 1 | 1/15 (6.7%) | 1 |
Heartburn | 1/22 (4.5%) | 1 | 1/21 (4.8%) | 1 | 2/21 (9.5%) | 2 | 1/18 (5.6%) | 1 | 1/21 (4.8%) | 1 | 1/17 (5.9%) | 1 | 0/20 (0%) | 0 | 2/15 (13.3%) | 2 |
Gingivitis | 1/22 (4.5%) | 1 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 1/17 (5.9%) | 1 | 1/20 (5%) | 1 | 0/15 (0%) | 0 |
Nausea | 11/22 (50%) | 14 | 6/21 (28.6%) | 7 | 9/21 (42.9%) | 11 | 10/18 (55.6%) | 12 | 11/21 (52.4%) | 12 | 10/17 (58.8%) | 13 | 11/20 (55%) | 12 | 8/15 (53.3%) | 8 |
Abdomen/GI Pain | 2/22 (9.1%) | 2 | 1/21 (4.8%) | 1 | 2/21 (9.5%) | 2 | 5/18 (27.8%) | 6 | 2/21 (9.5%) | 2 | 1/17 (5.9%) | 1 | 2/20 (10%) | 2 | 4/15 (26.7%) | 5 |
Taste Alteration | 2/22 (9.1%) | 2 | 0/21 (0%) | 0 | 2/21 (9.5%) | 2 | 0/18 (0%) | 0 | 1/21 (4.8%) | 1 | 1/17 (5.9%) | 1 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Vomiting | 5/22 (22.7%) | 5 | 4/21 (19%) | 4 | 4/21 (19%) | 5 | 4/18 (22.2%) | 5 | 1/21 (4.8%) | 1 | 4/17 (23.5%) | 4 | 5/20 (25%) | 5 | 3/15 (20%) | 3 |
Dehydration | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 2/21 (9.5%) | 2 | 0/18 (0%) | 0 | 1/21 (4.8%) | 1 | 1/17 (5.9%) | 1 | 1/20 (5%) | 1 | 1/15 (6.7%) | 1 |
Distension | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 1/21 (4.8%) | 1 | 1/18 (5.6%) | 1 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 1/20 (5%) | 1 | 0/15 (0%) | 0 |
Dry Mouth | 0/22 (0%) | 0 | 1/21 (4.8%) | 1 | 1/21 (4.8%) | 1 | 0/18 (0%) | 0 | 4/21 (19%) | 4 | 0/17 (0%) | 0 | 3/20 (15%) | 3 | 1/15 (6.7%) | 1 |
Thrush | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 1/21 (4.8%) | 2 | 1/18 (5.6%) | 1 | 1/21 (4.8%) | 1 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Mucositis | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 1/21 (4.8%) | 1 | 1/18 (5.6%) | 2 | 1/21 (4.8%) | 1 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 1/15 (6.7%) | 1 |
Mouth Sores | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 1/21 (4.8%) | 1 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Ulcer | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 1/21 (4.8%) | 1 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Ascites | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 1/18 (5.6%) | 1 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Periodontal Disease | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 1/18 (5.6%) | 1 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Gastritis | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 1/18 (5.6%) | 1 | 1/21 (4.8%) | 1 | 2/17 (11.8%) | 2 | 0/20 (0%) | 0 | 1/15 (6.7%) | 1 |
Dysgeusia | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 1/21 (4.8%) | 1 | 2/17 (11.8%) | 2 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Dyspepsia | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 1/21 (4.8%) | 1 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Indigestion | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 1/21 (4.8%) | 1 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Diverticulitis | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 1/21 (4.8%) | 1 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Intermittent Appetite Change | 0/22 (0%) | 0 | 1/21 (4.8%) | 1 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 1/17 (5.9%) | 1 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
GERD | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 1/17 (5.9%) | 1 | 0/20 (0%) | 0 | 2/15 (13.3%) | 2 |
Hemorrhoids | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 1/17 (5.9%) | 1 | 2/20 (10%) | 3 | 1/15 (6.7%) | 1 |
Flatulence | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 1/20 (5%) | 1 | 0/15 (0%) | 0 |
Anal Incontinence | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 1/20 (5%) | 1 | 0/15 (0%) | 0 |
General disorders | ||||||||||||||||
Fatigue | 19/22 (86.4%) | 27 | 13/21 (61.9%) | 16 | 16/21 (76.2%) | 20 | 14/18 (77.8%) | 15 | 17/21 (81%) | 20 | 17/17 (100%) | 26 | 14/20 (70%) | 16 | 14/15 (93.3%) | 16 |
Pain | 1/22 (4.5%) | 1 | 2/21 (9.5%) | 2 | 2/21 (9.5%) | 2 | 5/18 (27.8%) | 7 | 1/21 (4.8%) | 1 | 4/17 (23.5%) | 4 | 4/20 (20%) | 5 | 5/15 (33.3%) | 6 |
Speech Impairment | 2/22 (9.1%) | 2 | 6/21 (28.6%) | 6 | 4/21 (19%) | 4 | 4/18 (22.2%) | 4 | 7/21 (33.3%) | 7 | 4/17 (23.5%) | 5 | 8/20 (40%) | 8 | 1/15 (6.7%) | 1 |
Weight Loss | 10/22 (45.5%) | 11 | 1/21 (4.8%) | 1 | 5/21 (23.8%) | 5 | 3/18 (16.7%) | 4 | 7/21 (33.3%) | 8 | 4/17 (23.5%) | 4 | 4/20 (20%) | 4 | 5/15 (33.3%) | 5 |
Fever | 4/22 (18.2%) | 5 | 1/21 (4.8%) | 1 | 0/21 (0%) | 0 | 3/18 (16.7%) | 5 | 1/21 (4.8%) | 1 | 2/17 (11.8%) | 2 | 3/20 (15%) | 4 | 2/15 (13.3%) | 2 |
Insomnia | 7/22 (31.8%) | 8 | 2/21 (9.5%) | 2 | 5/21 (23.8%) | 5 | 4/18 (22.2%) | 5 | 7/21 (33.3%) | 7 | 6/17 (35.3%) | 6 | 3/20 (15%) | 3 | 4/15 (26.7%) | 4 |
Chills | 1/22 (4.5%) | 1 | 1/21 (4.8%) | 1 | 1/21 (4.8%) | 1 | 2/18 (11.1%) | 4 | 0/21 (0%) | 0 | 3/17 (17.6%) | 3 | 3/20 (15%) | 3 | 0/15 (0%) | 0 |
Weight Gain | 2/22 (9.1%) | 2 | 1/21 (4.8%) | 1 | 1/21 (4.8%) | 1 | 0/18 (0%) | 0 | 1/21 (4.8%) | 1 | 1/17 (5.9%) | 1 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Obesity | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 1/21 (4.8%) | 1 | 0/17 (0%) | 0 | 3/20 (15%) | 4 | 1/15 (6.7%) | 1 |
Flu-Like Syndrome | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 1/17 (5.9%) | 1 | 2/20 (10%) | 3 | 0/15 (0%) | 0 |
Hepatobiliary disorders | ||||||||||||||||
ALT, SGPT | 6/22 (27.3%) | 7 | 5/21 (23.8%) | 6 | 8/21 (38.1%) | 14 | 7/18 (38.9%) | 7 | 6/21 (28.6%) | 9 | 4/17 (23.5%) | 5 | 8/20 (40%) | 8 | 7/15 (46.7%) | 9 |
AST, SGOT | 4/22 (18.2%) | 4 | 5/21 (23.8%) | 8 | 9/21 (42.9%) | 10 | 3/18 (16.7%) | 3 | 5/21 (23.8%) | 5 | 6/17 (35.3%) | 10 | 6/20 (30%) | 6 | 6/15 (40%) | 7 |
Gilbert's Disease | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 1/17 (5.9%) | 1 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Immune system disorders | ||||||||||||||||
Allergic Reaction | 1/22 (4.5%) | 1 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 1/17 (5.9%) | 2 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Allergic Rhinitis | 2/22 (9.1%) | 2 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 3/18 (16.7%) | 3 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Rhinitis | 2/22 (9.1%) | 3 | 0/21 (0%) | 0 | 1/21 (4.8%) | 1 | 1/18 (5.6%) | 1 | 3/21 (14.3%) | 3 | 2/17 (11.8%) | 4 | 4/20 (20%) | 4 | 2/15 (13.3%) | 2 |
Allergy | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 1/21 (4.8%) | 1 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Allergy | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 1/21 (4.8%) | 1 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Sarcoidosis | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 1/20 (5%) | 1 | 0/15 (0%) | 0 |
Infections and infestations | ||||||||||||||||
Infection | 1/22 (4.5%) | 1 | 3/21 (14.3%) | 3 | 0/21 (0%) | 0 | 1/18 (5.6%) | 1 | 3/21 (14.3%) | 3 | 2/17 (11.8%) | 2 | 1/20 (5%) | 1 | 1/15 (6.7%) | 1 |
Opportunistic Infection | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 1/18 (5.6%) | 1 | 1/21 (4.8%) | 1 | 1/17 (5.9%) | 1 | 1/20 (5%) | 1 | 0/15 (0%) | 0 |
Herpes | 1/22 (4.5%) | 1 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Infection with Unknown ANC | 1/22 (4.5%) | 1 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Infection with Normal ANC | 1/22 (4.5%) | 1 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 1/18 (5.6%) | 1 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 1/20 (5%) | 1 | 0/15 (0%) | 0 |
Infection with Normal ANC | 1/22 (4.5%) | 3 | 1/21 (4.8%) | 1 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Oral Candidiasis | 0/22 (0%) | 0 | 1/21 (4.8%) | 1 | 1/21 (4.8%) | 1 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 1/17 (5.9%) | 1 | 1/20 (5%) | 1 | 0/15 (0%) | 0 |
Toe Infection | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 1/18 (5.6%) | 1 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Sore Throat | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 2/18 (11.1%) | 2 | 1/21 (4.8%) | 1 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Infection with Normal ANC | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 1/18 (5.6%) | 1 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Metabolism and nutrition disorders | ||||||||||||||||
Hyperglycemia | 18/22 (81.8%) | 35 | 8/21 (38.1%) | 10 | 17/21 (81%) | 38 | 10/18 (55.6%) | 20 | 11/21 (52.4%) | 17 | 9/17 (52.9%) | 18 | 10/20 (50%) | 20 | 9/15 (60%) | 10 |
Amylase | 1/22 (4.5%) | 1 | 0/21 (0%) | 0 | 1/21 (4.8%) | 1 | 2/18 (11.1%) | 4 | 5/21 (23.8%) | 15 | 0/17 (0%) | 0 | 1/20 (5%) | 2 | 0/15 (0%) | 0 |
Hypertriglyceridemia | 6/22 (27.3%) | 7 | 7/21 (33.3%) | 7 | 7/21 (33.3%) | 7 | 10/18 (55.6%) | 21 | 16/21 (76.2%) | 30 | 3/17 (17.6%) | 3 | 11/20 (55%) | 17 | 11/15 (73.3%) | 14 |
Hypoalbuminemia | 2/22 (9.1%) | 3 | 3/21 (14.3%) | 8 | 3/21 (14.3%) | 4 | 3/18 (16.7%) | 3 | 2/21 (9.5%) | 3 | 4/17 (23.5%) | 5 | 2/20 (10%) | 2 | 4/15 (26.7%) | 5 |
Hypophosphatemia | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 1/21 (4.8%) | 1 | 5/18 (27.8%) | 5 | 0/21 (0%) | 0 | 2/17 (11.8%) | 2 | 0/20 (0%) | 0 | 1/15 (6.7%) | 1 |
Lipase | 1/22 (4.5%) | 1 | 0/21 (0%) | 0 | 1/21 (4.8%) | 1 | 7/18 (38.9%) | 8 | 9/21 (42.9%) | 23 | 1/17 (5.9%) | 1 | 3/20 (15%) | 3 | 3/15 (20%) | 5 |
Hypokalemia | 3/22 (13.6%) | 4 | 1/21 (4.8%) | 1 | 3/21 (14.3%) | 4 | 3/18 (16.7%) | 3 | 4/21 (19%) | 6 | 4/17 (23.5%) | 5 | 4/20 (20%) | 7 | 3/15 (20%) | 4 |
Hypercholesteremia | 9/22 (40.9%) | 12 | 6/21 (28.6%) | 6 | 3/21 (14.3%) | 3 | 13/18 (72.2%) | 17 | 16/21 (76.2%) | 22 | 4/17 (23.5%) | 4 | 8/20 (40%) | 8 | 9/15 (60%) | 10 |
Alkaline Phosphatase | 6/22 (27.3%) | 14 | 2/21 (9.5%) | 2 | 2/21 (9.5%) | 4 | 4/18 (22.2%) | 5 | 5/21 (23.8%) | 11 | 2/17 (11.8%) | 2 | 2/20 (10%) | 2 | 1/15 (6.7%) | 1 |
Low Bicarbonate | 2/22 (9.1%) | 2 | 2/21 (9.5%) | 5 | 2/21 (9.5%) | 2 | 7/18 (38.9%) | 7 | 2/21 (9.5%) | 2 | 1/17 (5.9%) | 1 | 1/20 (5%) | 1 | 2/15 (13.3%) | 2 |
Hyperbilirubinemia | 2/22 (9.1%) | 3 | 3/21 (14.3%) | 3 | 3/21 (14.3%) | 5 | 3/18 (16.7%) | 7 | 3/21 (14.3%) | 6 | 1/17 (5.9%) | 1 | 1/20 (5%) | 1 | 3/15 (20%) | 3 |
Creatinine | 6/22 (27.3%) | 7 | 3/21 (14.3%) | 3 | 2/21 (9.5%) | 2 | 5/18 (27.8%) | 5 | 4/21 (19%) | 6 | 5/17 (29.4%) | 5 | 4/20 (20%) | 4 | 2/15 (13.3%) | 3 |
Hypoglycemia | 3/22 (13.6%) | 3 | 0/21 (0%) | 0 | 5/21 (23.8%) | 5 | 1/18 (5.6%) | 2 | 1/21 (4.8%) | 1 | 1/17 (5.9%) | 1 | 2/20 (10%) | 2 | 0/15 (0%) | 0 |
Hypercalcemia | 1/22 (4.5%) | 1 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 1/21 (4.8%) | 1 | 0/17 (0%) | 0 | 1/20 (5%) | 1 | 1/15 (6.7%) | 1 |
Hyperkalemia | 2/22 (9.1%) | 2 | 0/21 (0%) | 0 | 3/21 (14.3%) | 3 | 1/18 (5.6%) | 1 | 4/21 (19%) | 6 | 1/17 (5.9%) | 1 | 2/20 (10%) | 2 | 2/15 (13.3%) | 3 |
Hypermagnesemia | 1/22 (4.5%) | 1 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 1/18 (5.6%) | 1 | 1/21 (4.8%) | 1 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Hyperuricemia | 5/22 (22.7%) | 5 | 1/21 (4.8%) | 1 | 5/21 (23.8%) | 6 | 2/18 (11.1%) | 2 | 6/21 (28.6%) | 9 | 1/17 (5.9%) | 1 | 1/20 (5%) | 2 | 0/15 (0%) | 0 |
Hypocalcemia | 1/22 (4.5%) | 1 | 1/21 (4.8%) | 3 | 3/21 (14.3%) | 7 | 1/18 (5.6%) | 1 | 2/21 (9.5%) | 2 | 3/17 (17.6%) | 3 | 2/20 (10%) | 2 | 1/15 (6.7%) | 1 |
Hyponatremia | 5/22 (22.7%) | 6 | 3/21 (14.3%) | 4 | 2/21 (9.5%) | 2 | 3/18 (16.7%) | 3 | 4/21 (19%) | 6 | 1/17 (5.9%) | 1 | 0/20 (0%) | 0 | 1/15 (6.7%) | 1 |
Hypomagnesemia | 1/22 (4.5%) | 1 | 3/21 (14.3%) | 3 | 2/21 (9.5%) | 2 | 1/18 (5.6%) | 1 | 1/21 (4.8%) | 1 | 0/17 (0%) | 0 | 1/20 (5%) | 1 | 1/15 (6.7%) | 1 |
Hyperlipidemia | 1/22 (4.5%) | 1 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 1/18 (5.6%) | 1 | 1/21 (4.8%) | 1 | 0/17 (0%) | 0 | 1/20 (5%) | 1 | 0/15 (0%) | 0 |
High Chloride Serum | 3/22 (13.6%) | 4 | 3/21 (14.3%) | 6 | 5/21 (23.8%) | 7 | 6/18 (33.3%) | 9 | 2/21 (9.5%) | 4 | 5/17 (29.4%) | 9 | 2/20 (10%) | 3 | 2/15 (13.3%) | 2 |
Hyperphosphatemia | 4/22 (18.2%) | 7 | 1/21 (4.8%) | 1 | 2/21 (9.5%) | 2 | 1/18 (5.6%) | 1 | 3/21 (14.3%) | 4 | 2/17 (11.8%) | 2 | 4/20 (20%) | 4 | 0/15 (0%) | 0 |
High Bicarbonate | 2/22 (9.1%) | 2 | 0/21 (0%) | 0 | 1/21 (4.8%) | 1 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 2/20 (10%) | 2 | 0/15 (0%) | 0 |
Low Chloride Serum | 2/22 (9.1%) | 2 | 1/21 (4.8%) | 1 | 1/21 (4.8%) | 1 | 1/18 (5.6%) | 1 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 1/20 (5%) | 2 | 0/15 (0%) | 0 |
Low Protein Serum | 2/22 (9.1%) | 2 | 1/21 (4.8%) | 2 | 3/21 (14.3%) | 5 | 1/18 (5.6%) | 1 | 1/21 (4.8%) | 1 | 3/17 (17.6%) | 6 | 2/20 (10%) | 3 | 2/15 (13.3%) | 2 |
High Protein Serum | 2/22 (9.1%) | 2 | 0/21 (0%) | 0 | 1/21 (4.8%) | 1 | 0/18 (0%) | 0 | 2/21 (9.5%) | 2 | 1/17 (5.9%) | 1 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Low Uric Acid | 2/22 (9.1%) | 3 | 0/21 (0%) | 0 | 2/21 (9.5%) | 2 | 1/18 (5.6%) | 1 | 0/21 (0%) | 0 | 1/17 (5.9%) | 1 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Hypernatremia | 2/22 (9.1%) | 3 | 2/21 (9.5%) | 2 | 2/21 (9.5%) | 2 | 2/18 (11.1%) | 2 | 1/21 (4.8%) | 1 | 3/17 (17.6%) | 4 | 0/20 (0%) | 0 | 2/15 (13.3%) | 2 |
Proteinuria | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 2/21 (9.5%) | 3 | 0/18 (0%) | 0 | 1/21 (4.8%) | 1 | 3/17 (17.6%) | 6 | 2/20 (10%) | 2 | 0/15 (0%) | 0 |
Hyperalbuminenia | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 1/21 (4.8%) | 2 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 2/15 (13.3%) | 2 |
Creatine Phosphokinase | 0/22 (0%) | 0 | 1/21 (4.8%) | 1 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Musculoskeletal and connective tissue disorders | ||||||||||||||||
Muscle Weakness | 11/22 (50%) | 16 | 5/21 (23.8%) | 5 | 9/21 (42.9%) | 10 | 11/18 (61.1%) | 14 | 7/21 (33.3%) | 7 | 11/17 (64.7%) | 14 | 4/20 (20%) | 4 | 4/15 (26.7%) | 5 |
Gait/Walking | 5/22 (22.7%) | 5 | 5/21 (23.8%) | 5 | 7/21 (33.3%) | 8 | 6/18 (33.3%) | 7 | 6/21 (28.6%) | 7 | 8/17 (47.1%) | 8 | 10/20 (50%) | 10 | 4/15 (26.7%) | 4 |
Involuntary Movement | 1/22 (4.5%) | 1 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 1/20 (5%) | 1 | 0/15 (0%) | 0 |
Unsteady Gait | 2/22 (9.1%) | 2 | 0/21 (0%) | 0 | 1/21 (4.8%) | 1 | 1/18 (5.6%) | 1 | 1/21 (4.8%) | 1 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Back Pain | 5/22 (22.7%) | 5 | 2/21 (9.5%) | 2 | 1/21 (4.8%) | 1 | 3/18 (16.7%) | 3 | 1/21 (4.8%) | 1 | 1/17 (5.9%) | 1 | 1/20 (5%) | 1 | 2/15 (13.3%) | 2 |
Joint Pain | 2/22 (9.1%) | 2 | 0/21 (0%) | 0 | 2/21 (9.5%) | 2 | 5/18 (27.8%) | 6 | 0/21 (0%) | 0 | 3/17 (17.6%) | 4 | 0/20 (0%) | 0 | 2/15 (13.3%) | 2 |
Knee Pain | 1/22 (4.5%) | 1 | 1/21 (4.8%) | 1 | 0/21 (0%) | 0 | 2/18 (11.1%) | 2 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Ankle Pain | 1/22 (4.5%) | 1 | 1/21 (4.8%) | 1 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 1/15 (6.7%) | 1 |
Shoulder Pain | 2/22 (9.1%) | 2 | 0/21 (0%) | 0 | 1/21 (4.8%) | 1 | 0/18 (0%) | 0 | 2/21 (9.5%) | 2 | 1/17 (5.9%) | 1 | 1/20 (5%) | 1 | 0/15 (0%) | 0 |
Jaw Pain | 2/22 (9.1%) | 2 | 1/21 (4.8%) | 1 | 0/21 (0%) | 0 | 1/18 (5.6%) | 1 | 0/21 (0%) | 0 | 1/17 (5.9%) | 1 | 0/20 (0%) | 0 | 2/15 (13.3%) | 2 |
Wrist Pain | 2/22 (9.1%) | 2 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Muscle Cramps | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 1/21 (4.8%) | 1 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 1/17 (5.9%) | 1 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Hip Pain | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 1/21 (4.8%) | 1 | 1/18 (5.6%) | 1 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 1/15 (6.7%) | 1 |
Neck Pain | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 3/18 (16.7%) | 3 | 1/21 (4.8%) | 1 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Fracture | 0/22 (0%) | 0 | 1/21 (4.8%) | 1 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Bilateral Hands/Feet Swelling | 0/22 (0%) | 0 | 1/21 (4.8%) | 1 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 2/17 (11.8%) | 2 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Muscles Twitching | 0/22 (0%) | 0 | 1/21 (4.8%) | 1 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Gout | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 1/17 (5.9%) | 1 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Osteopenia | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 1/20 (5%) | 1 | 0/15 (0%) | 0 |
Deep Tendon Reflexes - Limb | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 1/20 (5%) | 1 | 2/15 (13.3%) | 2 |
Left Hemiparesis | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 1/15 (6.7%) | 1 |
Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||||||
Polyp in the Cardia | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 1/17 (5.9%) | 1 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Hepatic Hemangioma | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 1/20 (5%) | 1 | 0/15 (0%) | 0 |
Cervical Lipoma | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 1/20 (5%) | 1 | 0/15 (0%) | 0 |
Asymptomatic Thyroid Nodule | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 1/15 (6.7%) | 1 |
Nervous system disorders | ||||||||||||||||
Syncope | 1/22 (4.5%) | 1 | 3/21 (14.3%) | 3 | 1/21 (4.8%) | 1 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 1/20 (5%) | 1 | 2/15 (13.3%) | 2 |
Headache | 10/22 (45.5%) | 13 | 9/21 (42.9%) | 11 | 9/21 (42.9%) | 9 | 14/18 (77.8%) | 15 | 12/21 (57.1%) | 17 | 8/17 (47.1%) | 10 | 13/20 (65%) | 16 | 8/15 (53.3%) | 9 |
Dizziness | 7/22 (31.8%) | 7 | 6/21 (28.6%) | 6 | 9/21 (42.9%) | 10 | 6/18 (33.3%) | 6 | 8/21 (38.1%) | 9 | 11/17 (64.7%) | 13 | 9/20 (45%) | 9 | 3/15 (20%) | 3 |
Ataxia | 1/22 (4.5%) | 1 | 1/21 (4.8%) | 1 | 1/21 (4.8%) | 1 | 0/18 (0%) | 0 | 4/21 (19%) | 4 | 5/17 (29.4%) | 5 | 2/20 (10%) | 2 | 1/15 (6.7%) | 1 |
Pyramidal Tract Dysfunction | 10/22 (45.5%) | 10 | 5/21 (23.8%) | 5 | 7/21 (33.3%) | 7 | 6/18 (33.3%) | 6 | 7/21 (33.3%) | 7 | 8/17 (47.1%) | 8 | 8/20 (40%) | 8 | 4/15 (26.7%) | 4 |
Cognitive Disturbance | 6/22 (27.3%) | 7 | 4/21 (19%) | 4 | 7/21 (33.3%) | 7 | 5/18 (27.8%) | 5 | 5/21 (23.8%) | 5 | 5/17 (29.4%) | 5 | 5/20 (25%) | 5 | 3/15 (20%) | 3 |
Confusion | 3/22 (13.6%) | 4 | 0/21 (0%) | 0 | 4/21 (19%) | 5 | 5/18 (27.8%) | 5 | 1/21 (4.8%) | 1 | 4/17 (23.5%) | 4 | 4/20 (20%) | 4 | 3/15 (20%) | 3 |
Memory Impairment | 9/22 (40.9%) | 9 | 5/21 (23.8%) | 5 | 7/21 (33.3%) | 7 | 8/18 (44.4%) | 9 | 8/21 (38.1%) | 8 | 7/17 (41.2%) | 7 | 4/20 (20%) | 4 | 4/15 (26.7%) | 4 |
Anxiety | 3/22 (13.6%) | 3 | 1/21 (4.8%) | 1 | 3/21 (14.3%) | 3 | 2/18 (11.1%) | 2 | 3/21 (14.3%) | 3 | 5/17 (29.4%) | 5 | 4/20 (20%) | 4 | 0/15 (0%) | 0 |
Agitation | 1/22 (4.5%) | 1 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 2/18 (11.1%) | 2 | 2/21 (9.5%) | 2 | 2/17 (11.8%) | 2 | 1/20 (5%) | 1 | 0/15 (0%) | 0 |
Neuropathy | 2/22 (9.1%) | 2 | 0/21 (0%) | 0 | 2/21 (9.5%) | 2 | 0/18 (0%) | 0 | 1/21 (4.8%) | 1 | 1/17 (5.9%) | 1 | 1/20 (5%) | 2 | 1/15 (6.7%) | 1 |
Neuropathy - Motor | 1/22 (4.5%) | 1 | 2/21 (9.5%) | 2 | 2/21 (9.5%) | 2 | 1/18 (5.6%) | 1 | 0/21 (0%) | 0 | 2/17 (11.8%) | 2 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Neuropathy - Sensory | 4/22 (18.2%) | 4 | 3/21 (14.3%) | 4 | 2/21 (9.5%) | 2 | 2/18 (11.1%) | 4 | 2/21 (9.5%) | 2 | 4/17 (23.5%) | 4 | 4/20 (20%) | 4 | 4/15 (26.7%) | 4 |
Tingling | 3/22 (13.6%) | 3 | 2/21 (9.5%) | 2 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 3/21 (14.3%) | 3 | 3/17 (17.6%) | 3 | 4/20 (20%) | 5 | 1/15 (6.7%) | 1 |
Dysesthesias | 1/22 (4.5%) | 1 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Numbness | 4/22 (18.2%) | 4 | 2/21 (9.5%) | 2 | 3/21 (14.3%) | 3 | 3/18 (16.7%) | 4 | 2/21 (9.5%) | 2 | 4/17 (23.5%) | 5 | 7/20 (35%) | 8 | 1/15 (6.7%) | 1 |
Radiculopathy | 1/22 (4.5%) | 1 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Neuralgia | 1/22 (4.5%) | 1 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Seizure | 5/22 (22.7%) | 5 | 6/21 (28.6%) | 6 | 5/21 (23.8%) | 14 | 7/18 (38.9%) | 10 | 11/21 (52.4%) | 13 | 8/17 (47.1%) | 12 | 8/20 (40%) | 8 | 2/15 (13.3%) | 2 |
Somnolence | 2/22 (9.1%) | 2 | 1/21 (4.8%) | 1 | 1/21 (4.8%) | 1 | 1/18 (5.6%) | 1 | 0/21 (0%) | 0 | 3/17 (17.6%) | 4 | 5/20 (25%) | 5 | 4/15 (26.7%) | 4 |
Tremor | 2/22 (9.1%) | 2 | 3/21 (14.3%) | 3 | 2/21 (9.5%) | 2 | 2/18 (11.1%) | 2 | 2/21 (9.5%) | 2 | 3/17 (17.6%) | 3 | 3/20 (15%) | 3 | 7/15 (46.7%) | 7 |
Low Phenytoin | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 1/21 (4.8%) | 1 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Psychosis | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 1/21 (4.8%) | 1 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Mood Changes | 0/22 (0%) | 0 | 1/21 (4.8%) | 1 | 2/21 (9.5%) | 2 | 0/18 (0%) | 0 | 1/21 (4.8%) | 1 | 1/17 (5.9%) | 1 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
CN VI Palsy | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 1/18 (5.6%) | 1 | 0/21 (0%) | 0 | 1/17 (5.9%) | 1 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Short Term Memory | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 1/21 (4.8%) | 1 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Dystonic Meige Syndrome | 0/22 (0%) | 0 | 1/21 (4.8%) | 1 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Left VII CN Palsy | 0/22 (0%) | 0 | 1/21 (4.8%) | 1 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Disorientation | 0/22 (0%) | 0 | 1/21 (4.8%) | 1 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Light Headedness | 0/22 (0%) | 0 | 1/21 (4.8%) | 1 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Restlessness | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 2/17 (11.8%) | 2 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Hyperreflexia | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 1/17 (5.9%) | 1 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Apraxia | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 1/20 (5%) | 1 | 1/15 (6.7%) | 1 |
Facial Droop | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 1/20 (5%) | 1 | 0/15 (0%) | 0 |
Psychiatric disorders | ||||||||||||||||
Depression | 3/22 (13.6%) | 4 | 2/21 (9.5%) | 2 | 2/21 (9.5%) | 2 | 4/18 (22.2%) | 5 | 8/21 (38.1%) | 8 | 5/17 (29.4%) | 6 | 2/20 (10%) | 2 | 4/15 (26.7%) | 4 |
Renal and urinary disorders | ||||||||||||||||
Urinary Tract Infection | 1/22 (4.5%) | 1 | 1/21 (4.8%) | 1 | 1/21 (4.8%) | 1 | 3/18 (16.7%) | 3 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 1/20 (5%) | 1 | 0/15 (0%) | 0 |
Pain | 1/22 (4.5%) | 1 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Urinary Frequency | 4/22 (18.2%) | 5 | 2/21 (9.5%) | 3 | 1/21 (4.8%) | 1 | 5/18 (27.8%) | 6 | 2/21 (9.5%) | 2 | 3/17 (17.6%) | 4 | 3/20 (15%) | 3 | 2/15 (13.3%) | 2 |
Renal Pain | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 1/21 (4.8%) | 1 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 1/17 (5.9%) | 1 | 1/20 (5%) | 1 | 0/15 (0%) | 0 |
Membranous Glomerulonephritis | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 1/21 (4.8%) | 1 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Stress Incontinence | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 1/21 (4.8%) | 1 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Hematuria | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 1/18 (5.6%) | 1 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Dysuria | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 1/21 (4.8%) | 1 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Urinary Incontinence | 0/22 (0%) | 0 | 2/21 (9.5%) | 3 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 1/20 (5%) | 1 | 1/15 (6.7%) | 1 |
Bladder Spasms | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 1/17 (5.9%) | 1 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Burning During Urination | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 1/17 (5.9%) | 1 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Kidney Stones | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 1/20 (5%) | 1 | 0/15 (0%) | 0 |
Reproductive system and breast disorders | ||||||||||||||||
Erectile Dysfunction | 1/22 (4.5%) | 1 | 0/21 (0%) | 0 | 1/21 (4.8%) | 1 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 1/20 (5%) | 1 | 0/15 (0%) | 0 |
Libido | 1/22 (4.5%) | 1 | 1/21 (4.8%) | 1 | 2/21 (9.5%) | 2 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 1/20 (5%) | 1 | 0/15 (0%) | 0 |
Breast Pain | 1/22 (4.5%) | 1 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Irregular Menses | 0/22 (0%) | 0 | 1/21 (4.8%) | 1 | 1/21 (4.8%) | 1 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Orgasmic dyfunction | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 1/21 (4.8%) | 1 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Vaginal Dryness | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 1/21 (4.8%) | 1 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Breast Tenderness | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 1/17 (5.9%) | 1 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Respiratory, thoracic and mediastinal disorders | ||||||||||||||||
Dyspnea | 3/22 (13.6%) | 3 | 1/21 (4.8%) | 1 | 1/21 (4.8%) | 1 | 4/18 (22.2%) | 5 | 3/21 (14.3%) | 4 | 5/17 (29.4%) | 6 | 3/20 (15%) | 5 | 2/15 (13.3%) | 2 |
Pneumonitis | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 1/17 (5.9%) | 1 | 4/20 (20%) | 4 | 0/15 (0%) | 0 |
Bronchospasm | 2/22 (9.1%) | 3 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Cough | 8/22 (36.4%) | 10 | 3/21 (14.3%) | 3 | 3/21 (14.3%) | 4 | 7/18 (38.9%) | 8 | 3/21 (14.3%) | 4 | 2/17 (11.8%) | 2 | 6/20 (30%) | 8 | 3/15 (20%) | 4 |
Upper Respiratory Infection | 3/22 (13.6%) | 6 | 3/21 (14.3%) | 3 | 0/21 (0%) | 0 | 3/18 (16.7%) | 3 | 1/21 (4.8%) | 1 | 1/17 (5.9%) | 1 | 1/20 (5%) | 1 | 2/15 (13.3%) | 2 |
Paranasal Sinus Reactions | 1/22 (4.5%) | 1 | 0/21 (0%) | 0 | 1/21 (4.8%) | 1 | 0/18 (0%) | 0 | 1/21 (4.8%) | 1 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 1/15 (6.7%) | 1 |
Chest Pain | 5/22 (22.7%) | 6 | 1/21 (4.8%) | 1 | 0/21 (0%) | 0 | 2/18 (11.1%) | 2 | 1/21 (4.8%) | 1 | 3/17 (17.6%) | 3 | 1/20 (5%) | 1 | 1/15 (6.7%) | 1 |
Wheezing | 1/22 (4.5%) | 2 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 1/15 (6.7%) | 1 |
Vital Capacity | 1/22 (4.5%) | 1 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Voice Changes | 2/22 (9.1%) | 2 | 1/21 (4.8%) | 1 | 1/21 (4.8%) | 1 | 1/18 (5.6%) | 1 | 0/21 (0%) | 0 | 1/17 (5.9%) | 1 | 0/20 (0%) | 0 | 1/15 (6.7%) | 1 |
Hiccoughs | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 2/21 (9.5%) | 2 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Sinus Congestion | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 1/21 (4.8%) | 1 | 1/18 (5.6%) | 1 | 0/21 (0%) | 0 | 1/17 (5.9%) | 1 | 1/20 (5%) | 1 | 1/15 (6.7%) | 1 |
Throat Pain | 0/22 (0%) | 0 | 1/21 (4.8%) | 1 | 0/21 (0%) | 0 | 2/18 (11.1%) | 3 | 0/21 (0%) | 0 | 2/17 (11.8%) | 2 | 1/20 (5%) | 1 | 0/15 (0%) | 0 |
Pleural Effusion | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 1/18 (5.6%) | 1 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 1/20 (5%) | 1 | 0/15 (0%) | 0 |
Pneumothorax | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 1/21 (4.8%) | 1 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Aspiration | 0/22 (0%) | 0 | 1/21 (4.8%) | 1 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Edema | 0/22 (0%) | 0 | 1/21 (4.8%) | 1 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Bronchitis | 0/22 (0%) | 0 | 1/21 (4.8%) | 1 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 1/15 (6.7%) | 1 |
Tachycardia | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 1/17 (5.9%) | 1 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
CO2 Serum Low | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 1/20 (5%) | 1 | 1/15 (6.7%) | 1 |
Skin and subcutaneous tissue disorders | ||||||||||||||||
Rash | 8/22 (36.4%) | 8 | 5/21 (23.8%) | 5 | 6/21 (28.6%) | 10 | 1/18 (5.6%) | 1 | 4/21 (19%) | 4 | 11/17 (64.7%) | 12 | 6/20 (30%) | 7 | 4/15 (26.7%) | 4 |
Pruritus | 4/22 (18.2%) | 4 | 0/21 (0%) | 0 | 3/21 (14.3%) | 3 | 3/18 (16.7%) | 3 | 2/21 (9.5%) | 2 | 1/17 (5.9%) | 2 | 2/20 (10%) | 2 | 2/15 (13.3%) | 2 |
Dry Skin | 3/22 (13.6%) | 3 | 2/21 (9.5%) | 2 | 4/21 (19%) | 4 | 11/18 (61.1%) | 13 | 19/21 (90.5%) | 19 | 9/17 (52.9%) | 9 | 9/20 (45%) | 9 | 10/15 (66.7%) | 10 |
Alopecia | 3/22 (13.6%) | 3 | 4/21 (19%) | 4 | 5/21 (23.8%) | 5 | 4/18 (22.2%) | 4 | 5/21 (23.8%) | 5 | 1/17 (5.9%) | 1 | 3/20 (15%) | 3 | 6/15 (40%) | 6 |
Bruising | 2/22 (9.1%) | 2 | 1/21 (4.8%) | 1 | 1/21 (4.8%) | 1 | 2/18 (11.1%) | 2 | 0/21 (0%) | 0 | 1/17 (5.9%) | 1 | 1/20 (5%) | 1 | 2/15 (13.3%) | 2 |
Cellulitis | 2/22 (9.1%) | 2 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 2/21 (9.5%) | 2 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 1/15 (6.7%) | 1 |
Shingles | 1/22 (4.5%) | 1 | 0/21 (0%) | 0 | 1/21 (4.8%) | 1 | 1/18 (5.6%) | 1 | 2/21 (9.5%) | 2 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 1/15 (6.7%) | 1 |
Nail Changes | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 1/21 (4.8%) | 1 | 0/18 (0%) | 0 | 1/21 (4.8%) | 1 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Acne | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 1/18 (5.6%) | 1 | 1/21 (4.8%) | 1 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Skin Lesion | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 3/18 (16.7%) | 3 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Facial Hair Growth | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 1/18 (5.6%) | 1 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Erythema Multiforme | 0/22 (0%) | 0 | 1/21 (4.8%) | 1 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 1/21 (4.8%) | 1 | 1/17 (5.9%) | 1 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Cheilosis | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 1/21 (4.8%) | 1 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 1/15 (6.7%) | 1 |
Ecchymosis Lower Extremity | 0/22 (0%) | 0 | 1/21 (4.8%) | 1 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Uticaria | 0/22 (0%) | 0 | 1/21 (4.8%) | 1 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Burn | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 1/17 (5.9%) | 1 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Ulceration | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 1/17 (5.9%) | 1 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Wound Complication | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 1/17 (5.9%) | 1 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Skin Sensitivity | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 1/20 (5%) | 1 | 0/15 (0%) | 0 |
Dermatitis | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 1/20 (5%) | 1 | 0/15 (0%) | 0 |
Flushing | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 1/20 (5%) | 1 | 0/15 (0%) | 0 |
Hyperpigmentation | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 1/20 (5%) | 1 | 1/15 (6.7%) | 1 |
Agraphesthesia | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 1/20 (5%) | 1 | 0/15 (0%) | 0 |
Injection Site Reaction | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 1/15 (6.7%) | 1 |
Vascular disorders | ||||||||||||||||
Thrombosis | 4/22 (18.2%) | 5 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 1/18 (5.6%) | 1 | 2/21 (9.5%) | 2 | 1/17 (5.9%) | 1 | 1/20 (5%) | 1 | 0/15 (0%) | 0 |
Hemorrhage | 1/22 (4.5%) | 1 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 3/18 (16.7%) | 4 | 1/21 (4.8%) | 2 | 0/17 (0%) | 0 | 3/20 (15%) | 3 | 1/15 (6.7%) | 1 |
Thrombophlebitis | 1/22 (4.5%) | 1 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Varicosities | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 1/21 (4.8%) | 1 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 0/20 (0%) | 0 | 0/15 (0%) | 0 |
Deep Vein Thrombosis | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 1/21 (4.8%) | 1 | 1/17 (5.9%) | 1 | 0/20 (0%) | 0 | 1/15 (6.7%) | 1 |
Necrosis | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 1/20 (5%) | 1 | 0/15 (0%) | 0 |
Peripheral Vascular Disease | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 1/20 (5%) | 1 | 0/15 (0%) | 0 |
Vein Injury | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/21 (0%) | 0 | 0/18 (0%) | 0 | 0/21 (0%) | 0 | 0/17 (0%) | 0 | 1/20 (5%) | 1 | 0/15 (0%) | 0 |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title | John F de Groot, Chair Ad Interim, Neuro-Oncology |
---|---|
Organization | The University of Texas (UT) MD Anderson Cancer Center |
Phone | 713-745-3072 |
jdegroot@mdanderson.org |
- 2004-0662
- MDA-ID-02586
- NCI-6636
- MDA-2004-0662
- CDR0000432954
- NCI-2009-00076