A Study Of SU011248 Plus Paclitaxel Versus Bevacizumab Plus Paclitaxel In Patients With Advanced Breast Cancer

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00373256
• Collaborator: (none)
• Enrollment: 488
• Locations: 250
• Arms: 2
• Duration (Months): 57
• Patients Per Site: 2
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

To compare treatment with SU011248 plus paclitaxel versus bevacizumab plus paclitaxel to determine which treatment works better against breast cancer

Condition or Disease	Intervention/Treatment	Phase
Breast Neoplasms	Drug: Sunitinib; Drug: paclitaxel; Drug: bevacizumab; Drug: paclitaxel	Phase 3

Detailed Description

On May 27, 2009, the independent Data Monitoring Committee (DMC) reviewed the progress of Study A6181094. The DMC determined Study A6181094 had met pre-specified futility criteria and was unlikely to meet its primary endpoint to demonstrate a statistically significant improvement in progression-free survival (PFS) in patients treated with sunitinib plus paclitaxel versus bevacizumab plus paclitaxel. Pfizer notified clinical trial investigators involved in the study and regulatory agencies of these findings. Enrollment in this study has been stopped.

Study Design

• Study Type: Interventional
• Actual Enrollment: 488 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 3 Study Of SU011248 In Combination With Paclitaxel Versus Bevacizumab With Paclitaxel In The First-Line Advanced Disease Setting In Patients Having Breast Cancer
• Study Start Date: Nov 1, 2006
• Actual Primary Completion Date: Jun 1, 2009
• Actual Study Completion Date: Aug 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: A	Drug: Sunitinib; Sunitinib 25 mg daily by oral capsules with titration up to 37.5 mg,; Other Names: SU011248, Sutent ; Drug: paclitaxel; Paclitaxel 90 mg/m2 IV, 3 weekly doses every 28 days until progression or unacceptable toxicity.
Active Comparator: B	Drug: bevacizumab; Bevacizumab 10 mg/kg IV every 2 weeks.; Other Names: Avastin ; Drug: paclitaxel; Paclitaxel 90 mg/m2 IV, 3 weekly doses every 28 days until progression or unacceptable toxicity.

Outcome Measures

Primary Outcome Measures

1. Progression-Free Survival (PFS) [From date of randomization through Day 1 and every 8 weeks thereafter up to 18 months or death]

   Time from date of randomization to the date of the first documentation of objective tumor progression or death due to any cause, whichever occurred first. PFS = (first event date minus randomization date +1) divided by 30.4

Secondary Outcome Measures

1. Number of Participants With Objective Response [From date of randomization through Day 1 and every 8 weeks thereafter up to 18 months]

   Objective response = participants with confirmed complete response (CR) or partial response (PR) according to the Response Evaluation Criteria in Solid Tumors (RECIST). A CR was defined as the disappearance of all target lesions. A PR was defined as a > = 30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions.

2. Duration of Response (DR) [From date of randomization through Day 1 and every 8 weeks thereafter up to 18 months or death due to any cause]

   DR=time from the first documentation of objective tumor response (CR or PR) that was subsequently confirmed to first documentation of objective disease progression or death due to any cause, whichever was first. DR was calculated as [the date response ended (ie, date of progressive disease or death) minus first CR or PR date that was subsequently confirmed +1)] divided by 30.4.

3. Overall Survival (OS) [From date of randomization up to 5 years. Survival follow-up changed to 28-days after treatment discontinuation when study was discontinued.]

   OS was defined as the time from date of randomization to death due to any cause. OS (in months) was calculated as (date of death minus randomization date +1) divided by 30.4.

4. Percentage of Participants Surviving at 1 and 2 Years [Year 1, Year 2]

   Percentage of those surviving at the end of one year or end of 2 years from the first dose of study treatment.

5. European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (EORTC QLQ-C30) [Day 1 of Cycles 1 through 7 and then odd-numbered cycles thereafter until 18 months]

   EORTC QLQ-C30: global health/QoL, functional domains (physical, role, cognitive, emotional, social), and symptom scales/items (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea). Recall period: past week; response range: not at all to very much, global/QOL range: very poor to excellent. Scale score range: 0 to 100. Higher functional/global QoL score = better functioning and higher symptom score = greater degree of symptoms.

6. EORTC QLQ Breast Cancer Module (BR23) [Day 1 of Cycles 1 through 7 and then odd-numbered cycles thereafter until 18 months]

   BR23: measured disease related symptoms of dry mouth, eye pain, hair loss, hot flushes, attractiveness, future health, sexual activity, arm/shoulder pain, breast pain, swollen breast, and skin problems on the breast. Recall period: past week; response range: not at all to very much. Scale score range: 0 to 100. Higher symptom score = greater degree of symptoms.

7. Euro Quality of Life-5 Dimension (EQ-5D) [Day 1 of Cycles 1 through 7 and then odd-numbered cycles thereafter until 18 months]

   EQ-5D: health status in 5 dimensions (mobility, self-care, pain/discomfort, anxiety/depression, usual activities). Three-level scale (1=no problem, 2=some problem, and 3=extreme problem). A single score between 1 and 3 is generated for each domain. For each subject, the outcome rating on the 5 domains could be mapped to a single index through an algorithm. The index ranges between 0 and 1, with the higher score indicating a better health state perceived by the subject.

8. EQ - Visual Analog Scale (EQ-VAS) [Day 1 of Cycles 1 through 7 and then odd-numbered cycles thereafter until 18 months]

   EQ-VAS score on the self-rated "thermometer," indicating the patient's own assessment of their health status from 0 (worst) to 100 (best) imaginable health state.

9. Biomarkers [Day 1 of Cycles 1 through 3 and 5, Day 8 of Cycle 1, and Day 15 of Cycle 1]

   Concentrations of plasma proteins (eg, soluble Vascular Endothelial Growth Factor Receptor 2 [VEGFR2] and VEGFR3, VEGF-A, placental growth factor [PlGF], soluble KIT, and possibly soluble PDGFRβ and PDGF) that may be associated with angiogenesis and tumor proliferation.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Diagnosis of advanced breast cancer.

• Measurable disease as per RECIST (Response Evaluation Criterion) in Solid Tumors or bone-only disease.

• ECOG (Eastern Cooperative Oncology Group) performance status 0 or 1.

Exclusion Criteria:

• No prior treatment with cytotoxics in the advanced disease setting.

• HER2/neu positive disease unless trastuzumab was previously received or is contraindicated.

• Treatment with a taxane in the adjuvant setting unless disease free interval >12 months after end of treatment.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pfizer Investigational Site	Bessemer	Alabama	United States	35022
2	Pfizer Investigational Site	Birmingham	Alabama	United States	35205
3	Pfizer Investigational Site	Birmingham	Alabama	United States	35209
4	Pfizer Investigational Site	Birmingham	Alabama	United States	35211
5	Pfizer Investigational Site	Birmingham	Alabama	United States	35213
6	Pfizer Investigational Site	Birmingham	Alabama	United States	35235
7	Pfizer Investigational Site	Daphne	Alabama	United States	36526
8	Pfizer Investigational Site	Mobile	Alabama	United States	36604
9	Pfizer Investigational Site	Mobile	Alabama	United States	36608
10	Pfizer Investigational Site	Flagstaff	Arizona	United States	86001
11	Pfizer Investigational Site	Sedona	Arizona	United States	86336
12	Pfizer Investigational Site	Hot Springs	Arkansas	United States	71913
13	Pfizer Investigational Site	Anaheim	California	United States	92807
14	Pfizer Investigational Site	Antioch	California	United States	94509
15	Pfizer Investigational Site	Antioch	California	United States	94531
16	Pfizer Investigational Site	Baldwin Park	California	United States	91706
17	Pfizer Investigational Site	Bellflower	California	United States	90706
18	Pfizer Investigational Site	Fontana	California	United States	92335
19	Pfizer Investigational Site	Fountain Valley	California	United States	92708
20	Pfizer Investigational Site	Gilroy	California	United States	95020
21	Pfizer Investigational Site	Hawthorne	California	United States	90250
22	Pfizer Investigational Site	Hayward	California	United States	94545
23	Pfizer Investigational Site	Irvine	California	United States	92618
24	Pfizer Investigational Site	La Jolla	California	United States	92093
25	Pfizer Investigational Site	Long Beach	California	United States	90806
26	Pfizer Investigational Site	Los Angeles	California	United States	90025
27	Pfizer Investigational Site	Los Angeles	California	United States	90027
28	Pfizer Investigational Site	Los Angeles	California	United States	90034
29	Pfizer Investigational Site	Martinez	California	United States	94553
30	Pfizer Investigational Site	Milpitas	California	United States	95035
31	Pfizer Investigational Site	Modesto	California	United States	95356
32	Pfizer Investigational Site	Mountain View	California	United States	94041
33	Pfizer Investigational Site	Oakland	California	United States	94611
34	Pfizer Investigational Site	Ontario	California	United States	91761
35	Pfizer Investigational Site	Orange	California	United States	92868
36	Pfizer Investigational Site	Oxnard	California	United States	93030
37	Pfizer Investigational Site	Panorama City	California	United States	91402
38	Pfizer Investigational Site	Pinole	California	United States	94564
39	Pfizer Investigational Site	Riverside	California	United States	92505
40	Pfizer Investigational Site	Sacramento	California	United States	95817
41	Pfizer Investigational Site	San Diego	California	United States	92108
42	Pfizer Investigational Site	San Diego	California	United States	92120
43	Pfizer Investigational Site	San Francisco	California	United States	94080
44	Pfizer Investigational Site	San Francisco	California	United States	94115
45	Pfizer Investigational Site	San Francisco	California	United States	94118
46	Pfizer Investigational Site	San Jose	California	United States	95119
47	Pfizer Investigational Site	San Sacramento	California	United States	95825
48	Pfizer Investigational Site	Santa Clara	California	United States	95051
49	Pfizer Investigational Site	Santa Monica	California	United States	90404
50	Pfizer Investigational Site	Union City	California	United States	94587
51	Pfizer Investigational Site	Vallejo	California	United States	94589
52	Pfizer Investigational Site	Walnut Creek	California	United States	94596
53	Pfizer Investigational Site	Woodland Hills	California	United States	91365
54	Pfizer Investigational Site	Aurora	Colorado	United States	80012
55	Pfizer Investigational Site	Boulder	Colorado	United States	80303
56	Pfizer Investigational Site	Colorado Springs	Colorado	United States	80907
57	Pfizer Investigational Site	Colorado Springs	Colorado	United States	80909
58	Pfizer Investigational Site	Denver	Colorado	United States	80218
59	Pfizer Investigational Site	Denver	Colorado	United States	80220
60	Pfizer Investigational Site	Lakewood	Colorado	United States	80228
61	Pfizer Investigational Site	Littleton	Colorado	United States	80120
62	Pfizer Investigational Site	Lone Tree	Colorado	United States	80214
63	Pfizer Investigational Site	Longmont	Colorado	United States	80501
64	Pfizer Investigational Site	Parker	Colorado	United States	80138
65	Pfizer Investigational Site	Thornton	Colorado	United States	80260
66	Pfizer Investigational Site	Norwalk	Connecticut	United States	06856
67	Pfizer Investigational Site	Boca Raton	Florida	United States	33428
68	Pfizer Investigational Site	Coral Springs	Florida	United States	33065
69	Pfizer Investigational Site	Davie	Florida	United States	33328
70	Pfizer Investigational Site	Hollywood	Florida	United States	33021
71	Pfizer Investigational Site	Inverness	Florida	United States	34452
72	Pfizer Investigational Site	Lakeland	Florida	United States	33805
73	Pfizer Investigational Site	Melbourne	Florida	United States	32901
74	Pfizer Investigational Site	Miami	Florida	United States	33125
75	Pfizer Investigational Site	Miami	Florida	United States	33129
76	Pfizer Investigational Site	Miami	Florida	United States	33133
77	Pfizer Investigational Site	Orlando	Florida	United States	32806
78	Pfizer Investigational Site	Pembroke Pines	Florida	United States	33028
79	Pfizer Investigational Site	Tampa	Florida	United States	33612-9497
80	Pfizer Investigational Site	Winter Park	Florida	United States	32789
81	Pfizer Investigational Site	Atlanta	Georgia	United States	30341
82	Pfizer Investigational Site	Atlanta	Georgia	United States	30342
83	Pfizer Investigational Site	Columbus	Georgia	United States	31902
84	Pfizer Investigational Site	Columbus	Georgia	United States	31904
85	Pfizer Investigational Site	Decatur	Georgia	United States	30033
86	Pfizer Investigational Site	Macon	Georgia	United States	31217
87	Pfizer Investigational Site	Marietta	Georgia	United States	30060
88	Pfizer Investigational Site	Chicago	Illinois	United States	60612
89	Pfizer Investigational Site	Harvey	Illinois	United States	60426
90	Pfizer Investigational Site	Skokie	Illinois	United States	60076
91	Pfizer Investigational Site	Tinley Park	Illinois	United States	60477
92	Pfizer Investigational Site	Vernon Hills	Illinois	United States	60061
93	Pfizer Investigational Site	Avon	Indiana	United States	46123
94	Pfizer Investigational Site	Beech Grove	Indiana	United States	46107
95	Pfizer Investigational Site	Carmel	Indiana	United States	46032
96	Pfizer Investigational Site	Fishers	Indiana	United States	46037
97	Pfizer Investigational Site	Greenfield	Indiana	United States	46140
98	Pfizer Investigational Site	Indianapolis	Indiana	United States	46219
99	Pfizer Investigational Site	Indianapolis	Indiana	United States	46227
100	Pfizer Investigational Site	Indianapolis	Indiana	United States	46237
101	Pfizer Investigational Site	Indianapolis	Indiana	United States	46254
102	Pfizer Investigational Site	Indianapolis	Indiana	United States	46260
103	Pfizer Investigational Site	Jeffersonville	Indiana	United States	47130
104	Pfizer Investigational Site	Mooresville	Indiana	United States	46158
105	Pfizer Investigational Site	Munster	Indiana	United States	46321
106	Pfizer Investigational Site	New Albany	Indiana	United States	47150-6809
107	Pfizer Investigational Site	Kansas City	Kansas	United States	66112
108	Pfizer Investigational Site	Overland Park	Kansas	United States	66210
109	Pfizer Investigational Site	Louisville	Kentucky	United States	40202
110	Pfizer Investigational Site	Louisville	Kentucky	United States	40207
111	Pfizer Investigational Site	Louisville	Kentucky	United States	40217
112	Pfizer Investigational Site	Louisville	Kentucky	United States	40241
113	Pfizer Investigational Site	Louisville	Kentucky	United States	40245
114	Pfizer Investigational Site	Annapolis	Maryland	United States	21401
115	Pfizer Investigational Site	Baltimore	Maryland	United States	21202
116	Pfizer Investigational Site	Baltimore	Maryland	United States	21215
117	Pfizer Investigational Site	Baltimore	Maryland	United States	21225
118	Pfizer Investigational Site	Baltimore	Maryland	United States	21229
119	Pfizer Investigational Site	Columbia	Maryland	United States	21044
120	Pfizer Investigational Site	Randallstown	Maryland	United States	21133
121	Pfizer Investigational Site	Burlington	Massachusetts	United States	01805
122	Pfizer Investigational Site	Peabody	Massachusetts	United States	01960
123	Pfizer Investigational Site	Coon Rapids	Minnesota	United States	55433
124	Pfizer Investigational Site	Robbinsdale	Minnesota	United States	55422
125	Pfizer Investigational Site	Ocean Springs	Mississippi	United States	39564
126	Pfizer Investigational Site	Pascagoula	Mississippi	United States	39581
127	Pfizer Investigational Site	Columbia	Missouri	United States	65201
128	Pfizer Investigational Site	Kansas City	Missouri	United States	64111
129	Pfizer Investigational Site	Kansas City	Missouri	United States	64131
130	Pfizer Investigational Site	Kansas City	Missouri	United States	64154
131	Pfizer Investigational Site	Lee's Summit	Missouri	United States	64064
132	Pfizer Investigational Site	Fremont	Nebraska	United States	68025
133	Pfizer Investigational Site	Grand Island	Nebraska	United States	68803
134	Pfizer Investigational Site	Lincoln	Nebraska	United States	68502
135	Pfizer Investigational Site	Lincoln	Nebraska	United States	68506
136	Pfizer Investigational Site	Lincoln	Nebraska	United States	68510
137	Pfizer Investigational Site	Lincoln	Nebraska	United States	68516
138	Pfizer Investigational Site	Henderson	Nevada	United States	89052
139	Pfizer Investigational Site	Henderson	Nevada	United States	89074
140	Pfizer Investigational Site	Las Vegas	Nevada	United States	89102
141	Pfizer Investigational Site	Las Vegas	Nevada	United States	89106
142	Pfizer Investigational Site	Las Vegas	Nevada	United States	89109
143	Pfizer Investigational Site	Las Vegas	Nevada	United States	89128
144	Pfizer Investigational Site	Las Vegas	Nevada	United States	89148
145	Pfizer Investigational Site	Las Vegas	Nevada	United States	89169
146	Pfizer Investigational Site	Albuquerque	New Mexico	United States	87106
147	Pfizer Investigational Site	Albuquerque	New Mexico	United States	87109
148	Pfizer Investigational Site	Buffalo	New York	United States	14263
149	Pfizer Investigational Site	Corning	New York	United States	14830
150	Pfizer Investigational Site	Jamaica	New York	United States	11432
151	Pfizer Investigational Site	Mineola	New York	United States	11501
152	Pfizer Investigational Site	Cary	North Carolina	United States	27518
153	Pfizer Investigational Site	Clinton	North Carolina	United States	28328
154	Pfizer Investigational Site	Durham	North Carolina	United States	27710
155	Pfizer Investigational Site	Goldsboro	North Carolina	United States	27534
156	Pfizer Investigational Site	Hickory	North Carolina	United States	28602
157	Pfizer Investigational Site	Kenansville	North Carolina	United States	28349
158	Pfizer Investigational Site	Kinston	North Carolina	United States	28501
159	Pfizer Investigational Site	Lenoir	North Carolina	United States	28645
160	Pfizer Investigational Site	Pollocksville	North Carolina	United States	28573
161	Pfizer Investigational Site	Raleight	North Carolina	United States	27614
162	Pfizer Investigational Site	Raliegh	North Carolina	United States	27607
163	Pfizer Investigational Site	Richlands	North Carolina	United States	28574
164	Pfizer Investigational Site	Washington	North Carolina	United States	27889
165	Pfizer Investigational Site	Wilson	North Carolina	United States	27893
166	Pfizer Investigational Site	Winston-Salem	North Carolina	United States	27157
167	Pfizer Investigational Site	Canton	Ohio	United States	44718
168	Pfizer Investigational Site	Dover	Ohio	United States	44622
169	Pfizer Investigational Site	Eugene	Oregon	United States	97401
170	Pfizer Investigational Site	Portland	Oregon	United States	97213
171	Pfizer Investigational Site	Portland	Oregon	United States	97225
172	Pfizer Investigational Site	Portland	Oregon	United States	97227
173	Pfizer Investigational Site	Portland	Oregon	United States	97239
174	Pfizer Investigational Site	Springfield	Oregon	United States	97477
175	Pfizer Investigational Site	Tualatin	Oregon	United States	97062
176	Pfizer Investigational Site	Allentown	Pennsylvania	United States	18104
177	Pfizer Investigational Site	Bethlehem	Pennsylvania	United States	18015
178	Pfizer Investigational Site	Ephrata	Pennsylvania	United States	17522
179	Pfizer Investigational Site	Hershey	Pennsylvania	United States	17033
180	Pfizer Investigational Site	Kingston	Pennsylvania	United States	18704
181	Pfizer Investigational Site	Pittsburgh	Pennsylvania	United States	15213
182	Pfizer Investigational Site	Pittsburgh	Pennsylvania	United States	15232
183	Pfizer Investigational Site	Sayre	Pennsylvania	United States	18840
184	Pfizer Investigational Site	Charleston	South Carolina	United States	29406-9173
185	Pfizer Investigational Site	Easley	South Carolina	United States	29640
186	Pfizer Investigational Site	Greenville	South Carolina	United States	29605
187	Pfizer Investigational Site	Greenville	South Carolina	United States	29615
188	Pfizer Investigational Site	Seneca	South Carolina	United States	29672
189	Pfizer Investigational Site	Spartanburg	South Carolina	United States	29307
190	Pfizer Investigational Site	Bristol	Tennessee	United States	37620
191	Pfizer Investigational Site	Kingsport	Tennessee	United States	37660
192	Pfizer Investigational Site	Amarillo	Texas	United States	79106
193	Pfizer Investigational Site	Antonio	Texas	United States	78212
194	Pfizer Investigational Site	Austin	Texas	United States	78705
195	Pfizer Investigational Site	Austin	Texas	United States	78731
196	Pfizer Investigational Site	Austin	Texas	United States	78758
197	Pfizer Investigational Site	Austin	Texas	United States	78759-5249
198	Pfizer Investigational Site	Bedford	Texas	United States	76022
199	Pfizer Investigational Site	Corpus Christi	Texas	United States	78405
200	Pfizer Investigational Site	Dallas	Texas	United States	75231
201	Pfizer Investigational Site	Dallas	Texas	United States	75246
202	Pfizer Investigational Site	Fort Worth	Texas	United States	76104
203	Pfizer Investigational Site	Fort Worth	Texas	United States	76132
204	Pfizer Investigational Site	Fort Worth	Texas	United States	76177
205	Pfizer Investigational Site	Forth Worth	Texas	United States	76177
206	Pfizer Investigational Site	Houston	Texas	United States	77024
207	Pfizer Investigational Site	Houston	Texas	United States	77090
208	Pfizer Investigational Site	Houston	Texas	United States	77429
209	Pfizer Investigational Site	Kerrville	Texas	United States	78217
210	Pfizer Investigational Site	Longview	Texas	United States	75601
211	Pfizer Investigational Site	Midland	Texas	United States	79701-5946
212	Pfizer Investigational Site	Round Rock	Texas	United States	78665
213	Pfizer Investigational Site	Round Rock	Texas	United States	78681
214	Pfizer Investigational Site	Round Rock	Texas	United States	78745
215	Pfizer Investigational Site	San Antonio	Texas	United States	78217
216	Pfizer Investigational Site	San Antonio	Texas	United States	78258
217	Pfizer Investigational Site	San Marcos	Texas	United States	78666
218	Pfizer Investigational Site	Shenandoah	Texas	United States	77384
219	Pfizer Investigational Site	Tyler	Texas	United States	75702
220	Pfizer Investigational Site	Waco	Texas	United States	76712
221	Pfizer Investigational Site	Ogden	Utah	United States	84403-3274
222	Pfizer Investigational Site	Arlington	Virginia	United States	22205
223	Pfizer Investigational Site	Christiansburg	Virginia	United States	24073
224	Pfizer Investigational Site	Fairfax	Virginia	United States	22031
225	Pfizer Investigational Site	Leesburg	Virginia	United States	20176
226	Pfizer Investigational Site	Norton	Virginia	United States	24273
227	Pfizer Investigational Site	Roanoke	Virginia	United States	24014
228	Pfizer Investigational Site	Salem	Virginia	United States	24153
229	Pfizer Investigational Site	Woodbridge	Virginia	United States	22191
230	Pfizer Investigational Site	Wytheville	Virginia	United States	24382
231	Pfizer Investigational Site	Federal Way	Washington	United States	98003
232	Pfizer Investigational Site	Kennewick	Washington	United States	99336
233	Pfizer Investigational Site	Lakewood	Washington	United States	98499
234	Pfizer Investigational Site	Moses Lake	Washington	United States	98837
235	Pfizer Investigational Site	Puyallup	Washington	United States	98372
236	Pfizer Investigational Site	Tacoma	Washington	United States	98405
237	Pfizer Investigational Site	Vancouver	Washington	United States	98684
238	Pfizer Investigational Site	Vancouver	Washington	United States	98686
239	Pfizer Investigational Site	Wenatchee	Washington	United States	98801
240	Pfizer Investigational Site	Huntington	West Virginia	United States	25701
241	Pfizer Investigational Site	Morgantown	West Virginia	United States	26506
242	Pfizer Investigational Site	Berlin		Germany	14195
243	Pfizer Investigational Site	Hamburg		Germany	20246
244	Pfizer Investigational Site	Trier		Germany	54290
245	Pfizer Investigational Site	Cremona		Italy	26100
246	Pfizer Investigational Site	Grosseto		Italy	58100
247	Pfizer Investigational Site	Olbia		Italy	07026
248	Pfizer Investigational Site	Cabueñes	Gijon	Spain	33394
249	Pfizer Investigational Site	Guadalajara		Spain	19002
250	Pfizer Investigational Site	Madrid		Spain	28033

Sponsors and Collaborators

• Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• To obtain contact information for a study center near you, click here.

Publications

None provided.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT00373256
• Other Study ID Numbers: A6181094
• First Posted: Sep 8, 2006
• Last Update Posted: Sep 10, 2012
• Last Verified: Sep 1, 2012

• Keywords provided by Pfizer: Breast cancer; advanced; sunitinib; bevacizumab; paclitaxel; Phase 3
• Additional relevant MeSH terms: Breast Neoplasms; Paclitaxel; Albumin-Bound Paclitaxel; Bevacizumab; Sunitinib

Study Results

Participant Flow

Arm/Group Title	Sunitinib + Paclitaxel	Bevacizumab + Paclitaxel
Arm/Group Description	Starting sunitinib doses of 25 milligrams (mg) daily. After Cycle 1, escalation to 37.5 mg daily was permitted in the absence of complicated neutropenia and if all 3 Cycle 1 paclitaxel doses were successfully administered at 90 milligrams per square meter (mg/m^2), at discretion of the investigator. Paclitaxel could have been reduced to 65 mg/m^2 based on tolerability; re-escalation to 80 or 90 mg/m^2 upon recovery was permitted.	Bevacizumab 10 milligrams per kilogram (mg/kg); infusion duration according to standard of care. Paclitaxel starting dose of 90 mg/m^2, as a 1 hour infusion. Paclitaxel could have been reduced to 65 mg/m^2 based on tolerability; re-escalation to 80 or 90 mg/m^2 upon recovery was permitted.
Period Title: Overall Study
STARTED	241	247
Treated	235	236
COMPLETED	0	0
NOT COMPLETED	241	247

Baseline Characteristics

Arm/Group Title	Sunitinib + Paclitaxel	Bevacizumab + Paclitaxel	Total
Arm/Group Description	Starting sunitinib doses of 25 mg daily. After Cycle 1, escalation to 37.5 mg daily was permitted in the absence of complicated neutropenia and if all 3 Cycle 1 paclitaxel doses were successfully administered at 90 mg/m^2, at discretion of the investigator. Paclitaxel could have been reduced to 65 mg/m^2 based on tolerability; re-escalation to 80 or 90 mg/m^2 upon recovery was permitted.	Bevacizumab 10 mg/kg; infusion duration according to standard of care. Paclitaxel starting dose of 90 mg/m^2, as a 1 hour infusion. Paclitaxel could have been reduced to 65 mg/m^2 based on tolerability; re-escalation to 80 or 90 mg/m^2 upon recovery was permitted.	Total of all reporting groups
Overall Participants	241	247	488
Age, Customized (Number) [Number]
18 to 44 years	38 15.8%	40 16.2%	78 16%
45 to 64 years	144 59.8%	137 55.5%	281 57.6%
more than 65 years	59 24.5%	70 28.3%	129 26.4%
Sex: Female, Male (Count of Participants)
Female	240 99.6%	247 100%	487 99.8%
Male	1 0.4%	0 0%	1 0.2%

Outcome Measures

1. Primary Outcome

Title	Progression-Free Survival (PFS)
Description	Time from date of randomization to the date of the first documentation of objective tumor progression or death due to any cause, whichever occurred first. PFS = (first event date minus randomization date +1) divided by 30.4
Time Frame	From date of randomization through Day 1 and every 8 weeks thereafter up to 18 months or death

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) population included all patients who were randomized.

Arm/Group Title	Sunitinib + Paclitaxel	Bevacizumab + Paclitaxel
Arm/Group Description	Starting sunitinib doses of 25 mg daily. After Cycle 1, escalation to 37.5 mg daily was permitted in the absence of complicated neutropenia and if all 3 Cycle 1 paclitaxel doses were successfully administered at 90 mg/m^2, at discretion of the investigator. Paclitaxel could have been reduced to 65 mg/m^2 based on tolerability; re-escalation to 80 or 90 mg/m^2 upon recovery was permitted.	Bevacizumab 10 mg/kg; infusion duration according to standard of care. Paclitaxel starting dose of 90 mg/m^2, as a 1 hour infusion. Paclitaxel could have been reduced to 65 mg/m^2 based on tolerability; re-escalation to 80 or 90 mg/m^2 upon recovery was permitted.
Measure Participants	242	243
Median (95% Confidence Interval) [Months]	7.4	9.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sunitinib + Paclitaxel, Bevacizumab + Paclitaxel
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9986
	Comments	p-value from 1-sided log-rank stratified for prior adjuvant chemotherapy, hormone receptor status, disease-free interval from prior adjuvant treatment. Stratification factors from Interactive Voice Randomization System.
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.6299
	Confidence Interval	(2-Sided) 95%; 1.1793 to 2.2527
	Parameter Dispersion	Type: Value:
	Estimation Comments	Assuming proportional hazards, a hazard ratio greater than 1 indicated a reduction in hazard rate in favor Bevacizumab + Paclitaxel.

2. Secondary Outcome

Title	Number of Participants With Objective Response
Description	Objective response = participants with confirmed complete response (CR) or partial response (PR) according to the Response Evaluation Criteria in Solid Tumors (RECIST). A CR was defined as the disappearance of all target lesions. A PR was defined as a > = 30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions.
Time Frame	From date of randomization through Day 1 and every 8 weeks thereafter up to 18 months

Outcome Measure Data

Analysis Population Description

ITT

Arm/Group Title	Sunitinib + Paclitaxel	Bevacizumab + Paclitaxel
Arm/Group Description	Starting sunitinib doses of 25 mg daily. After Cycle 1, escalation to 37.5 mg daily was permitted in the absence of complicated neutropenia and if all 3 Cycle 1 paclitaxel doses were successfully administered at 90 mg/m^2, at discretion of the investigator. Paclitaxel could have been reduced to 65 mg/m^2 based on tolerability; re-escalation to 80 or 90 mg/m^2 upon recovery was permitted.	Bevacizumab 10 mg/kg; infusion duration according to standard of care. Paclitaxel starting dose of 90 mg/m^2, as a 1 hour infusion. Paclitaxel could have been reduced to 65 mg/m^2 based on tolerability; re-escalation to 80 or 90 mg/m^2 upon recovery was permitted.
Measure Participants	242	243
Number [participants]	78 32.4%	78 31.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sunitinib + Paclitaxel
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Objective Response Rate (ORR) (percent)
	Estimated Value	32.2
	Confidence Interval	(2-Sided) 95%; 26.4 to 38.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Bevacizumab + Paclitaxel
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Objective Response Rate (ORR) (percent)
	Estimated Value	32.1
	Confidence Interval	(2-Sided) 95%; 26.3 to 38.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Duration of Response (DR)
Description	DR=time from the first documentation of objective tumor response (CR or PR) that was subsequently confirmed to first documentation of objective disease progression or death due to any cause, whichever was first. DR was calculated as [the date response ended (ie, date of progressive disease or death) minus first CR or PR date that was subsequently confirmed +1)] divided by 30.4.
Time Frame	From date of randomization through Day 1 and every 8 weeks thereafter up to 18 months or death due to any cause

Outcome Measure Data

Analysis Population Description

ITT. DR was calculated for the subgroup of subjects with objective response. 78 subjects reported CR or PR response and were analyzed for DR in each treatment group.

Arm/Group Title	Sunitinib + Paclitaxel	Bevacizumab + Paclitaxel
Arm/Group Description	Starting sunitinib doses of 25 mg daily. After Cycle 1, escalation to 37.5 mg daily was permitted in the absence of complicated neutropenia and if all 3 Cycle 1 paclitaxel doses were successfully administered at 90 mg/m^2, at discretion of the investigator. Paclitaxel could have been reduced to 65 mg/m^2 based on tolerability; re-escalation to 80 or 90 mg/m^2 upon recovery was permitted.	Bevacizumab 10 mg/kg; infusion duration according to standard of care. Paclitaxel starting dose of 90 mg/m^2, as a 1 hour infusion. Paclitaxel could have been reduced to 65 mg/m^2 based on tolerability; re-escalation to 80 or 90 mg/m^2 upon recovery was permitted.
Measure Participants	78	78
Median (95% Confidence Interval) [Months]	6.3	14.8

4. Secondary Outcome

Title	Overall Survival (OS)
Description	OS was defined as the time from date of randomization to death due to any cause. OS (in months) was calculated as (date of death minus randomization date +1) divided by 30.4.
Time Frame	From date of randomization up to 5 years. Survival follow-up changed to 28-days after treatment discontinuation when study was discontinued.

Outcome Measure Data

Analysis Population Description

ITT. The median OS for bevacizumab + paclitaxel at the time of data cut off was not reached; therefore, it could not be calculated.

Arm/Group Title	Sunitinib + Paclitaxel	Bevacizumab + Paclitaxel
Arm/Group Description	Starting sunitinib doses of 25 mg daily. After Cycle 1, escalation to 37.5 mg daily was permitted in the absence of complicated neutropenia and if all 3 Cycle 1 paclitaxel doses were successfully administered at 90 mg/m^2, at discretion of the investigator. Paclitaxel could have been reduced to 65 mg/m^2 based on tolerability; re-escalation to 80 or 90 mg/m^2 upon recovery was permitted.	Bevacizumab 10 mg/kg; infusion duration according to standard of care. Paclitaxel starting dose of 90 mg/m^2, as a 1 hour infusion. Paclitaxel could have been reduced to 65 mg/m^2 based on tolerability; re-escalation to 80 or 90 mg/m^2 upon recovery was permitted.
Measure Participants	242	243
Median (95% Confidence Interval) [Months]	17.6	NA

5. Secondary Outcome

Title	Percentage of Participants Surviving at 1 and 2 Years
Description	Percentage of those surviving at the end of one year or end of 2 years from the first dose of study treatment.
Time Frame	Year 1, Year 2

Outcome Measure Data

Analysis Population Description

ITT.

Arm/Group Title	Sunitinib + Paclitaxel	Bevacizumab + Paclitaxel
Arm/Group Description	Starting sunitinib doses of 25 mg daily. After Cycle 1, escalation to 37.5 mg daily was permitted in the absence of complicated neutropenia and if all 3 Cycle 1 paclitaxel doses were successfully administered at 90 mg/m^2, at discretion of the investigator. Paclitaxel could have been reduced to 65 mg/m^2 based on tolerability; re-escalation to 80 or 90 mg/m^2 upon recovery was permitted.	Bevacizumab 10 mg/kg; infusion duration according to standard of care. Paclitaxel starting dose of 90 mg/m^2, as a 1 hour infusion. Paclitaxel could have been reduced to 65 mg/m^2 based on tolerability; re-escalation to 80 or 90 mg/m^2 upon recovery was permitted.
Measure Participants	242	243
Year 1	76.8 31.9%	83.7 33.9%
Year 2	35.5 14.7%	61.0 24.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sunitinib + Paclitaxel
	Comments	1 year
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage
	Estimated Value	76.8
	Confidence Interval	(2-Sided) 95%; 68.7 to 83.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Sunitinib + Paclitaxel
	Comments	2 years
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage
	Estimated Value	35.5
	Confidence Interval	(2-Sided) 95%; 20.9 to 50.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Bevacizumab + Paclitaxel
	Comments	1 year
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage
	Estimated Value	83.7
	Confidence Interval	(2-Sided) 95%; 76.0 to 89.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Bevacizumab + Paclitaxel
	Comments	2 years
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage
	Estimated Value	61.0
	Confidence Interval	(2-Sided) 95%; 43.2 to 74.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (EORTC QLQ-C30)
Description	EORTC QLQ-C30: global health/QoL, functional domains (physical, role, cognitive, emotional, social), and symptom scales/items (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea). Recall period: past week; response range: not at all to very much, global/QOL range: very poor to excellent. Scale score range: 0 to 100. Higher functional/global QoL score = better functioning and higher symptom score = greater degree of symptoms.
Time Frame	Day 1 of Cycles 1 through 7 and then odd-numbered cycles thereafter until 18 months

Outcome Measure Data

Analysis Population Description

ITT. EORTC QLQ-C30 evaluations were not analyzed since enrollment in this study was terminated early for futility.

Arm/Group Title	Sunitinib + Paclitaxel	Bevacizumab + Paclitaxel
Arm/Group Description	Starting sunitinib doses of 25 mg daily. After Cycle 1, escalation to 37.5 mg daily was permitted in the absence of complicated neutropenia and if all 3 Cycle 1 paclitaxel doses were successfully administered at 90 mg/m^2, at discretion of the investigator. Paclitaxel could have been reduced to 65 mg/m^2 based on tolerability; re-escalation to 80 or 90 mg/m^2 upon recovery was permitted.	Bevacizumab 10 mg/kg; infusion duration according to standard of care. Paclitaxel starting dose of 90 mg/m^2, as a 1 hour infusion. Paclitaxel could have been reduced to 65 mg/m^2 based on tolerability; re-escalation to 80 or 90 mg/m^2 upon recovery was permitted.
Measure Participants	0	0

7. Secondary Outcome

Title	EORTC QLQ Breast Cancer Module (BR23)
Description	BR23: measured disease related symptoms of dry mouth, eye pain, hair loss, hot flushes, attractiveness, future health, sexual activity, arm/shoulder pain, breast pain, swollen breast, and skin problems on the breast. Recall period: past week; response range: not at all to very much. Scale score range: 0 to 100. Higher symptom score = greater degree of symptoms.
Time Frame	Day 1 of Cycles 1 through 7 and then odd-numbered cycles thereafter until 18 months

Outcome Measure Data

Analysis Population Description

ITT. BR23 evaluations were not analyzed since enrollment in this study was terminated early for futility at the first interim analysis.

Arm/Group Title	Sunitinib + Paclitaxel	Bevacizumab + Paclitaxel
Arm/Group Description	Starting sunitinib doses of 25 mg daily. After Cycle 1, escalation to 37.5 mg daily was permitted in the absence of complicated neutropenia and if all 3 Cycle 1 paclitaxel doses were successfully administered at 90 mg/m^2, at discretion of the investigator. Paclitaxel could have been reduced to 65 mg/m^2 based on tolerability; re-escalation to 80 or 90 mg/m^2 upon recovery was permitted.	Bevacizumab 10 mg/kg; infusion duration according to standard of care. Paclitaxel starting dose of 90 mg/m^2, as a 1 hour infusion. Paclitaxel could have been reduced to 65 mg/m^2 based on tolerability; re-escalation to 80 or 90 mg/m^2 upon recovery was permitted.
Measure Participants	0	0

8. Secondary Outcome

Title	Euro Quality of Life-5 Dimension (EQ-5D)
Description	EQ-5D: health status in 5 dimensions (mobility, self-care, pain/discomfort, anxiety/depression, usual activities). Three-level scale (1=no problem, 2=some problem, and 3=extreme problem). A single score between 1 and 3 is generated for each domain. For each subject, the outcome rating on the 5 domains could be mapped to a single index through an algorithm. The index ranges between 0 and 1, with the higher score indicating a better health state perceived by the subject.
Time Frame	Day 1 of Cycles 1 through 7 and then odd-numbered cycles thereafter until 18 months

Outcome Measure Data

Analysis Population Description

ITT. EQ-5D evaluations were not analyzed since enrollment in this study was terminated early for futility at the first interim analysis.

Arm/Group Title	Sunitinib + Paclitaxel	Bevacizumab + Paclitaxel
Arm/Group Description	Starting sunitinib doses of 25 mg daily. After Cycle 1, escalation to 37.5 mg daily was permitted in the absence of complicated neutropenia and if all 3 Cycle 1 paclitaxel doses were successfully administered at 90 mg/m^2, at discretion of the investigator. Paclitaxel could have been reduced to 65 mg/m^2 based on tolerability; re-escalation to 80 or 90 mg/m^2 upon recovery was permitted.	Bevacizumab 10 mg/kg; infusion duration according to standard of care. Paclitaxel starting dose of 90 mg/m^2, as a 1 hour infusion. Paclitaxel could have been reduced to 65 mg/m^2 based on tolerability; re-escalation to 80 or 90 mg/m^2 upon recovery was permitted.
Measure Participants	0	0

9. Secondary Outcome

Title	EQ - Visual Analog Scale (EQ-VAS)
Description	EQ-VAS score on the self-rated "thermometer," indicating the patient's own assessment of their health status from 0 (worst) to 100 (best) imaginable health state.
Time Frame	Day 1 of Cycles 1 through 7 and then odd-numbered cycles thereafter until 18 months

Outcome Measure Data

Analysis Population Description

ITT. EQ-VAS evaluations were not analyzed since enrollment in this study was terminated early for futility at the first interim analysis.

Arm/Group Title	Sunitinib + Paclitaxel	Bevacizumab + Paclitaxel
Arm/Group Description	Starting sunitinib doses of 25 mg daily. After Cycle 1, escalation to 37.5 mg daily was permitted in the absence of complicated neutropenia and if all 3 Cycle 1 paclitaxel doses were successfully administered at 90 mg/m^2, at discretion of the investigator. Paclitaxel could have been reduced to 65 mg/m^2 based on tolerability; re-escalation to 80 or 90 mg/m^2 upon recovery was permitted.	Bevacizumab 10 mg/kg; infusion duration according to standard of care. Paclitaxel starting dose of 90 mg/m^2, as a 1 hour infusion. Paclitaxel could have been reduced to 65 mg/m^2 based on tolerability; re-escalation to 80 or 90 mg/m^2 upon recovery was permitted.
Measure Participants	0	0

10. Secondary Outcome

Title	Biomarkers
Description	Concentrations of plasma proteins (eg, soluble Vascular Endothelial Growth Factor Receptor 2 [VEGFR2] and VEGFR3, VEGF-A, placental growth factor [PlGF], soluble KIT, and possibly soluble PDGFRβ and PDGF) that may be associated with angiogenesis and tumor proliferation.
Time Frame	Day 1 of Cycles 1 through 3 and 5, Day 8 of Cycle 1, and Day 15 of Cycle 1

Outcome Measure Data

Analysis Population Description

ITT. Biomarker data were collected, but since the study was stopped early and there were too few events of OS, PFS, etc, data were not analyzed.

Arm/Group Title	Sunitinib + Paclitaxel	Bevacizumab + Paclitaxel
Arm/Group Description	Starting sunitinib doses of 25 mg daily. After Cycle 1, escalation to 37.5 mg daily was permitted in the absence of complicated neutropenia and if all 3 Cycle 1 paclitaxel doses were successfully administered at 90 mg/m^2, at discretion of the investigator. Paclitaxel could have been reduced to 65 mg/m^2 based on tolerability; re-escalation to 80 or 90 mg/m^2 upon recovery was permitted.	Bevacizumab 10 mg/kg; infusion duration according to standard of care. Paclitaxel starting dose of 90 mg/m^2, as a 1 hour infusion. Paclitaxel could have been reduced to 65 mg/m^2 based on tolerability; re-escalation to 80 or 90 mg/m^2 upon recovery was permitted.
Measure Participants	0	0

Adverse Events

Adverse Event Reporting Description	The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Arm/Group Title	Sunitinib + Paclitaxel		Bevacizumab + Paclitaxel
Arm/Group Description	Starting sunitinib doses of 25 mg daily. After Cycle 1, escalation to 37.5 mg daily was permitted in the absence of complicated neutropenia and if all 3 Cycle 1 paclitaxel doses were successfully administered at 90 mg/m^2, at discretion of the investigator. Paclitaxel could have been reduced to 65 mg/m^2 based on tolerability; re-escalation to 80 or 90 mg/m^2 upon recovery was permitted.		Bevacizumab 10 mg/kg; infusion duration according to standard of care. Paclitaxel starting dose of 90 mg/m^2, as a 1 hour infusion. Paclitaxel could have been reduced to 65 mg/m^2 based on tolerability; re-escalation to 80 or 90 mg/m^2 upon recovery was permitted.
All Cause Mortality
	Sunitinib + Paclitaxel		Bevacizumab + Paclitaxel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Sunitinib + Paclitaxel		Bevacizumab + Paclitaxel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	89/235 (37.9%)		85/242 (35.1%)
Blood and lymphatic system disorders
Anaemia	3/235 (1.3%)		1/242 (0.4%)
Febrile neutropenia	12/235 (5.1%)		3/242 (1.2%)
Leukopenia	1/235 (0.4%)		0/242 (0%)
Neutropenia	6/235 (2.6%)		2/242 (0.8%)
Pancytopenia	2/235 (0.9%)		0/242 (0%)
Thrombocytopenia	2/235 (0.9%)		0/242 (0%)
Cardiac disorders
Atrial fibrillation	1/235 (0.4%)		2/242 (0.8%)
Cardiac failure congestive	1/235 (0.4%)		1/242 (0.4%)
Cardiogenic shock	1/235 (0.4%)		0/242 (0%)
Cardiovascular disorder	0/235 (0%)		1/242 (0.4%)
Myocardial infarction	1/235 (0.4%)		0/242 (0%)
Myocardial ischaemia	1/235 (0.4%)		0/242 (0%)
Supraventricular extrasystoles	1/235 (0.4%)		0/242 (0%)
Gastrointestinal disorders
Abdominal pain	3/235 (1.3%)		4/242 (1.7%)
Abdominal pain lower	0/235 (0%)		2/242 (0.8%)
Abdominal pain upper	1/235 (0.4%)		0/242 (0%)
Ascites	1/235 (0.4%)		0/242 (0%)
Colitis ulcerative	1/235 (0.4%)		0/242 (0%)
Constipation	1/235 (0.4%)		2/242 (0.8%)
Diarrhoea	9/235 (3.8%)		3/242 (1.2%)
Diverticular perforation	1/235 (0.4%)		0/242 (0%)
Duodenitis	1/235 (0.4%)		0/242 (0%)
Gastric ulcer	1/235 (0.4%)		0/242 (0%)
Gastritis	1/235 (0.4%)		0/242 (0%)
Haematemesis	1/235 (0.4%)		0/242 (0%)
Ileus	1/235 (0.4%)		0/242 (0%)
Intestinal ischaemia	0/235 (0%)		1/242 (0.4%)
Lower gastrointestinal haemorrhage	1/235 (0.4%)		0/242 (0%)
Nausea	7/235 (3%)		0/242 (0%)
Oesophageal perforation	1/235 (0.4%)		0/242 (0%)
Pancreatitis	0/235 (0%)		2/242 (0.8%)
Rectal haemorrhage	1/235 (0.4%)		0/242 (0%)
Small intestinal obstruction	1/235 (0.4%)		0/242 (0%)
Vomiting	9/235 (3.8%)		1/242 (0.4%)
Intestinal obstruction	1/235 (0.4%)		0/242 (0%)
Intestinal perforation	0/235 (0%)		1/242 (0.4%)
Oesophagitis	0/235 (0%)		1/242 (0.4%)
Stomatitis	1/235 (0.4%)		0/242 (0%)
Haematochezia	0/235 (0%)		1/242 (0.4%)
General disorders
Asthenia	3/235 (1.3%)		2/242 (0.8%)
Chest pain	2/235 (0.9%)		0/242 (0%)
Disease progression	7/235 (3%)		7/242 (2.9%)
Fatigue	2/235 (0.9%)		2/242 (0.8%)
General physical health deterioration	4/235 (1.7%)		2/242 (0.8%)
Generalised oedema	1/235 (0.4%)		0/242 (0%)
Malaise	0/235 (0%)		1/242 (0.4%)
Mucosal inflammation	1/235 (0.4%)		1/242 (0.4%)
Non-cardiac chest pain	2/235 (0.9%)		0/242 (0%)
Oedema peripheral	0/235 (0%)		1/242 (0.4%)
Pain	1/235 (0.4%)		1/242 (0.4%)
Pyrexia	4/235 (1.7%)		5/242 (2.1%)
Hepatobiliary disorders
Cholecystitis	3/235 (1.3%)		0/242 (0%)
Hepatic cirrhosis	0/235 (0%)		1/242 (0.4%)
Hyperbilirubinaemia	1/235 (0.4%)		0/242 (0%)
Jaundice cholestatic	1/235 (0.4%)		0/242 (0%)
Immune system disorders
Drug hypersensitivity	1/235 (0.4%)		0/242 (0%)
Infections and infestations
Abscess	0/235 (0%)		1/242 (0.4%)
Appendicitis	0/235 (0%)		2/242 (0.8%)
Bacteraemia	1/235 (0.4%)		0/242 (0%)
Breast infection	1/235 (0.4%)		1/242 (0.4%)
Bronchitis	0/235 (0%)		2/242 (0.8%)
Catheter site infection	0/235 (0%)		1/242 (0.4%)
Cellulitis	1/235 (0.4%)		2/242 (0.8%)
Device related infection	3/235 (1.3%)		0/242 (0%)
Diverticulitis	0/235 (0%)		1/242 (0.4%)
Escherichia bacteraemia	1/235 (0.4%)		0/242 (0%)
Gastroenteritis	1/235 (0.4%)		1/242 (0.4%)
Gastrointestinal viral infection	0/235 (0%)		1/242 (0.4%)
Groin infection	1/235 (0.4%)		0/242 (0%)
Hepatitis A	1/235 (0.4%)		0/242 (0%)
Infection	0/235 (0%)		2/242 (0.8%)
Neutropenic sepsis	2/235 (0.9%)		0/242 (0%)
Pneumonia	3/235 (1.3%)		4/242 (1.7%)
Pneumonia klebsiella	0/235 (0%)		1/242 (0.4%)
Pneumonia primary atypical	1/235 (0.4%)		0/242 (0%)
Post procedural infection	0/235 (0%)		1/242 (0.4%)
Sepsis	2/235 (0.9%)		3/242 (1.2%)
Septic shock	0/235 (0%)		1/242 (0.4%)
Sinusitis	1/235 (0.4%)		0/242 (0%)
Staphylococcal sepsis	0/235 (0%)		2/242 (0.8%)
Streptococcal bacteraemia	1/235 (0.4%)		0/242 (0%)
Upper respiratory tract infection	0/235 (0%)		2/242 (0.8%)
Urinary tract infection	3/235 (1.3%)		5/242 (2.1%)
Viral diarrhoea	1/235 (0.4%)		0/242 (0%)
Wound infection	0/235 (0%)		1/242 (0.4%)
Device related sepsis	1/235 (0.4%)		0/242 (0%)
Pneumonia fungal	0/235 (0%)		1/242 (0.4%)
Skin infection	0/235 (0%)		1/242 (0.4%)
Urosepsis	0/235 (0%)		1/242 (0.4%)
Injury, poisoning and procedural complications
Femur fracture	0/235 (0%)		1/242 (0.4%)
Hip fracture	1/235 (0.4%)		1/242 (0.4%)
Humerus fracture	1/235 (0.4%)		1/242 (0.4%)
Joint sprain	0/235 (0%)		1/242 (0.4%)
Lumbar vertebral fracture	1/235 (0.4%)		0/242 (0%)
Meniscus lesion	0/235 (0%)		1/242 (0.4%)
Post procedural haematoma	0/235 (0%)		1/242 (0.4%)
Seroma	1/235 (0.4%)		0/242 (0%)
Wound dehiscence	1/235 (0.4%)		0/242 (0%)
Radius fracture	0/235 (0%)		1/242 (0.4%)
Wound necrosis	0/235 (0%)		1/242 (0.4%)
Investigations
Alanine aminotransferase increased	0/235 (0%)		1/242 (0.4%)
Ammonia increased	0/235 (0%)		1/242 (0.4%)
Aspartate aminotransferase increased	0/235 (0%)		1/242 (0.4%)
Blood magnesium decreased	0/235 (0%)		1/242 (0.4%)
Blood pressure increased	1/235 (0.4%)		0/242 (0%)
Ejection fraction decreased	1/235 (0.4%)		0/236 (0%)
Metabolism and nutrition disorders
Dehydration	15/235 (6.4%)		12/242 (5%)
Electrolyte imbalance	1/235 (0.4%)		0/242 (0%)
Failure to thrive	2/235 (0.9%)		0/242 (0%)
Hypocalcaemia	1/235 (0.4%)		2/242 (0.8%)
Hypoglycaemia	2/235 (0.9%)		0/242 (0%)
Hypokalaemia	3/235 (1.3%)		1/242 (0.4%)
Hyponatraemia	1/235 (0.4%)		0/242 (0%)
Hypovolaemia	1/235 (0.4%)		0/242 (0%)
Decreased appetite	0/235 (0%)		1/242 (0.4%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/235 (0.4%)		0/242 (0%)
Back pain	0/235 (0%)		1/242 (0.4%)
Bone pain	0/235 (0%)		1/242 (0.4%)
Muscular weakness	1/235 (0.4%)		1/242 (0.4%)
Musculoskeletal chest pain	1/235 (0.4%)		0/242 (0%)
Myalgia	1/235 (0.4%)		0/242 (0%)
Pain in extremity	1/235 (0.4%)		0/242 (0%)
Pathological fracture	1/235 (0.4%)		1/242 (0.4%)
Bursitis	0/235 (0%)		1/242 (0.4%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain	0/235 (0%)		1/242 (0.4%)
Metastases to meninges	0/235 (0%)		1/242 (0.4%)
Nervous system disorders
Cerebellar syndrome	0/235 (0%)		1/242 (0.4%)
Cerebrovascular accident	2/235 (0.9%)		1/242 (0.4%)
Convulsion	1/235 (0.4%)		0/242 (0%)
Dizziness	1/235 (0.4%)		0/242 (0%)
Headache	1/235 (0.4%)		2/242 (0.8%)
Myelitis transverse	1/235 (0.4%)		0/242 (0%)
Nerve compression	1/235 (0.4%)		0/242 (0%)
Syncope	3/235 (1.3%)		2/242 (0.8%)
Transient ischaemic attack	0/235 (0%)		2/242 (0.8%)
Cerebral infarction	0/235 (0%)		1/242 (0.4%)
Hydrocephalus	1/235 (0.4%)		0/242 (0%)
Lacunar infarction	0/235 (0%)		1/242 (0.4%)
Subarachnoid haemorrhage	1/235 (0.4%)		0/242 (0%)
Psychiatric disorders
Confusional state	0/235 (0%)		5/242 (2.1%)
Renal and urinary disorders
Nephrotic syndrome	1/235 (0.4%)		1/242 (0.4%)
Renal failure acute	2/235 (0.9%)		0/242 (0%)
Urethral obstruction	0/235 (0%)		1/242 (0.4%)
Urinary retention	0/235 (0%)		1/242 (0.4%)
Respiratory, thoracic and mediastinal disorders
Acute pulmonary oedema	0/235 (0%)		1/242 (0.4%)
Acute respiratory failure	1/235 (0.4%)		0/242 (0%)
Dyspnoea	6/235 (2.6%)		2/242 (0.8%)
Epistaxis	1/235 (0.4%)		3/242 (1.2%)
Haemoptysis	1/235 (0.4%)		2/242 (0.8%)
Pleural effusion	4/235 (1.7%)		1/242 (0.4%)
Pneumonitis	1/235 (0.4%)		1/242 (0.4%)
Pneumothorax	1/235 (0.4%)		0/242 (0%)
Pulmonary embolism	4/235 (1.7%)		4/242 (1.7%)
Respiratory failure	0/235 (0%)		1/242 (0.4%)
Stridor	1/235 (0.4%)		0/242 (0%)
Surgical and medical procedures
Mastectomy	0/235 (0%)		1/242 (0.4%)
Vascular disorders
Deep vein thrombosis	1/235 (0.4%)		2/242 (0.8%)
Hypertension	1/235 (0.4%)		0/242 (0%)
Hypotension	2/235 (0.9%)		2/242 (0.8%)
Aneurysm	1/235 (0.4%)		0/242 (0%)
Arterial rupture	1/235 (0.4%)		0/242 (0%)
Other (Not Including Serious) Adverse Events
	Sunitinib + Paclitaxel		Bevacizumab + Paclitaxel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	232/235 (98.7%)		239/242 (98.8%)
Blood and lymphatic system disorders
Anaemia	104/235 (44.3%)		65/242 (26.9%)
Leukopenia	63/235 (26.8%)		55/242 (22.7%)
Lymphopenia	17/235 (7.2%)		13/242 (5.4%)
Neutropenia	170/235 (72.3%)		98/242 (40.5%)
Thrombocytopenia	56/235 (23.8%)		15/242 (6.2%)
Febrile neutropenia	5/235 (2.1%)		4/242 (1.7%)
Granulocytopenia	2/235 (0.9%)		0/242 (0%)
Leukocytosis	1/235 (0.4%)		2/242 (0.8%)
Lymph node pain	0/235 (0%)		1/242 (0.4%)
Lymphadenopathy	1/235 (0.4%)		3/242 (1.2%)
Macrocytosis	2/235 (0.9%)		0/242 (0%)
Microcytosis	0/235 (0%)		1/242 (0.4%)
Neutrophilia	2/235 (0.9%)		0/242 (0%)
Splenomegaly	0/235 (0%)		2/242 (0.8%)
Pancytopenia	4/235 (1.7%)		0/242 (0%)
Cardiac disorders
Atrial fibrillation	1/235 (0.4%)		1/242 (0.4%)
Cardiac failure congestive	2/235 (0.9%)		4/242 (1.7%)
Cardiomegaly	0/235 (0%)		1/242 (0.4%)
Cardiotoxicity	1/235 (0.4%)		1/242 (0.4%)
Cyanosis	1/235 (0.4%)		0/242 (0%)
Intracardiac thrombus	1/235 (0.4%)		0/242 (0%)
Left ventricular dysfunction	4/235 (1.7%)		5/242 (2.1%)
Left ventricular hypertrophy	0/235 (0%)		1/242 (0.4%)
Palpitations	2/235 (0.9%)		6/242 (2.5%)
Pericardial effusion	1/235 (0.4%)		2/242 (0.8%)
Sinus tachycardia	1/235 (0.4%)		2/242 (0.8%)
Splinter haemorrhages	0/235 (0%)		1/242 (0.4%)
Tachycardia	8/235 (3.4%)		12/242 (5%)
Tachycardia paroxysmal	1/235 (0.4%)		0/242 (0%)
Ventricular extrasystoles	1/235 (0.4%)		0/242 (0%)
Congenital, familial and genetic disorders
Atrial septal defect	0/235 (0%)		1/242 (0.4%)
Ear and labyrinth disorders
Cerumen impaction	0/235 (0%)		1/242 (0.4%)
Deafness	1/235 (0.4%)		0/242 (0%)
Ear disorder	2/235 (0.9%)		1/242 (0.4%)
Ear haemorrhage	1/235 (0.4%)		0/242 (0%)
Ear pain	5/235 (2.1%)		3/242 (1.2%)
Tinnitus	3/235 (1.3%)		0/242 (0%)
Vertigo	2/235 (0.9%)		4/242 (1.7%)
Endocrine disorders
Cushingoid	0/235 (0%)		1/242 (0.4%)
Hyperparathyroidism	1/235 (0.4%)		0/242 (0%)
Hyperthyroidism	1/235 (0.4%)		0/242 (0%)
Hypothyroidism	6/235 (2.6%)		7/242 (2.9%)
Eye disorders
Lacrimation increased	14/235 (6%)		14/242 (5.8%)
Vision blurred	15/235 (6.4%)		9/242 (3.7%)
Blindness unilateral	1/235 (0.4%)		0/242 (0%)
Cataract	0/235 (0%)		1/242 (0.4%)
Conjunctival haemorrhage	3/235 (1.3%)		0/242 (0%)
Conjunctival oedema	1/235 (0.4%)		0/242 (0%)
Conjunctival pallor	0/235 (0%)		1/242 (0.4%)
Conjunctivitis	5/235 (2.1%)		7/242 (2.9%)
Dacryostenosis acquired	0/235 (0%)		1/242 (0.4%)
Diplopia	5/235 (2.1%)		2/242 (0.8%)
Dry eye	4/235 (1.7%)		6/242 (2.5%)
Eye disorder	1/235 (0.4%)		0/242 (0%)
Eye haemorrhage	1/235 (0.4%)		0/242 (0%)
Eye irritation	2/235 (0.9%)		1/242 (0.4%)
Eye pain	1/235 (0.4%)		2/242 (0.8%)
Eye pruritus	0/235 (0%)		2/242 (0.8%)
Eye swelling	1/235 (0.4%)		0/242 (0%)
Eyelid oedema	4/235 (1.7%)		0/242 (0%)
Eyelid ptosis	1/235 (0.4%)		0/242 (0%)
Eyelids pruritus	1/235 (0.4%)		0/242 (0%)
Glaucoma	1/235 (0.4%)		0/242 (0%)
Halo vision	1/235 (0.4%)		0/242 (0%)
Keratoconjunctivitis sicca	0/235 (0%)		1/242 (0.4%)
Mydriasis	1/235 (0.4%)		0/242 (0%)
Optic ischaemic neuropathy	1/235 (0.4%)		0/242 (0%)
Periorbital oedema	2/235 (0.9%)		1/242 (0.4%)
Photophobia	0/235 (0%)		1/242 (0.4%)
Pupils unequal	1/235 (0.4%)		1/242 (0.4%)
Retinopathy hypertensive	0/235 (0%)		1/242 (0.4%)
Scotoma	1/235 (0.4%)		0/242 (0%)
Visual acuity reduced	0/235 (0%)		4/242 (1.7%)
Visual impairment	1/235 (0.4%)		6/242 (2.5%)
Vitreous floaters	2/235 (0.9%)		0/242 (0%)
Vitreous haemorrhage	1/235 (0.4%)		0/242 (0%)
Gastrointestinal disorders
Abdominal pain	34/235 (14.5%)		36/242 (14.9%)
Abdominal pain upper	21/235 (8.9%)		7/242 (2.9%)
Constipation	69/235 (29.4%)		92/242 (38%)
Diarrhoea	145/235 (61.7%)		109/242 (45%)
Dry mouth	15/235 (6.4%)		12/242 (5%)
Dyspepsia	41/235 (17.4%)		31/242 (12.8%)
Gastrooesophageal reflux disease	28/235 (11.9%)		12/242 (5%)
Haemorrhoids	14/235 (6%)		10/242 (4.1%)
Nausea	118/235 (50.2%)		113/242 (46.7%)
Oral pain	21/235 (8.9%)		8/242 (3.3%)
Stomatitis	44/235 (18.7%)		23/242 (9.5%)
Vomiting	67/235 (28.5%)		58/242 (24%)
Abdominal discomfort	2/235 (0.9%)		2/242 (0.8%)
Abdominal distension	4/235 (1.7%)		8/242 (3.3%)
Abdominal pain lower	4/235 (1.7%)		3/242 (1.2%)
Abdominal tenderness	4/235 (1.7%)		1/242 (0.4%)
Anal fistula	1/235 (0.4%)		2/242 (0.8%)
Anorectal discomfort	1/235 (0.4%)		1/242 (0.4%)
Ascites	3/235 (1.3%)		5/242 (2.1%)
Chapped lips	2/235 (0.9%)		1/242 (0.4%)
Cheilitis	1/235 (0.4%)		1/242 (0.4%)
Cheilosis	1/235 (0.4%)		0/242 (0%)
Colitis	1/235 (0.4%)		0/242 (0%)
Defaecation urgency	0/235 (0%)		1/242 (0.4%)
Dental caries	1/235 (0.4%)		1/242 (0.4%)
Diarrhoea haemorrhagic	2/235 (0.9%)		0/242 (0%)
Diverticulum	2/235 (0.9%)		1/242 (0.4%)
Duodenogastric reflux	0/235 (0%)		1/242 (0.4%)
Dysphagia	9/235 (3.8%)		5/242 (2.1%)
Epigastric discomfort	0/235 (0%)		2/242 (0.8%)
Eructation	1/235 (0.4%)		1/242 (0.4%)
Faecal incontinence	1/235 (0.4%)		2/242 (0.8%)
Faeces discoloured	0/235 (0%)		1/242 (0.4%)
Flatulence	11/235 (4.7%)		7/242 (2.9%)
Food poisoning	1/235 (0.4%)		0/242 (0%)
Frequent bowel movements	1/235 (0.4%)		1/242 (0.4%)
Gastritis	1/235 (0.4%)		2/242 (0.8%)
Gastrointestinal haemorrhage	2/235 (0.9%)		0/242 (0%)
Gastrointestinal pain	1/235 (0.4%)		2/242 (0.8%)
Gastrointestinal sounds abnormal	1/235 (0.4%)		0/242 (0%)
Gingival bleeding	10/235 (4.3%)		4/242 (1.7%)
Gingival pain	2/235 (0.9%)		1/242 (0.4%)
Gingival recession	1/235 (0.4%)		0/242 (0%)
Gingival swelling	1/235 (0.4%)		0/242 (0%)
Gingivitis	3/235 (1.3%)		0/242 (0%)
Glossitis	2/235 (0.9%)		1/242 (0.4%)
Glossodynia	8/235 (3.4%)		3/242 (1.2%)
Haematochezia	3/235 (1.3%)		5/242 (2.1%)
Haemorrhoidal haemorrhage	2/235 (0.9%)		5/242 (2.1%)
Hyperchlorhydria	1/235 (0.4%)		0/242 (0%)
Lip dry	0/235 (0%)		1/242 (0.4%)
Lip ulceration	1/235 (0.4%)		1/242 (0.4%)
Melaena	3/235 (1.3%)		0/242 (0%)
Mouth ulceration	1/235 (0.4%)		2/242 (0.8%)
Oesophageal disorder	1/235 (0.4%)		0/242 (0%)
Oesophageal pain	2/235 (0.9%)		0/242 (0%)
Oesophagitis	2/235 (0.9%)		0/242 (0%)
Oral discomfort	1/235 (0.4%)		0/242 (0%)
Oral disorder	1/235 (0.4%)		0/242 (0%)
Pancreatitis	0/235 (0%)		1/242 (0.4%)
Paraesthesia oral	2/235 (0.9%)		1/242 (0.4%)
Perianal erythema	1/235 (0.4%)		0/242 (0%)
Periodontal disease	3/235 (1.3%)		1/242 (0.4%)
Peritonitis	0/235 (0%)		1/242 (0.4%)
Proctalgia	4/235 (1.7%)		1/242 (0.4%)
Rectal haemorrhage	7/235 (3%)		3/242 (1.2%)
Rectal ulcer	1/235 (0.4%)		0/242 (0%)
Regurgitation	1/235 (0.4%)		0/242 (0%)
Salivary gland disorder	0/235 (0%)		1/242 (0.4%)
Salivary hypersecretion	1/235 (0.4%)		0/242 (0%)
Sensitivity of teeth	0/235 (0%)		1/242 (0.4%)
Small intestinal perforation	0/235 (0%)		1/242 (0.4%)
Swollen tongue	1/235 (0.4%)		0/242 (0%)
Tongue disorder	1/235 (0.4%)		0/242 (0%)
Tongue ulceration	2/235 (0.9%)		0/242 (0%)
Tooth discolouration	1/235 (0.4%)		0/242 (0%)
Tooth disorder	0/235 (0%)		1/242 (0.4%)
Tooth erosion	1/235 (0.4%)		0/242 (0%)
Tooth loss	1/235 (0.4%)		0/242 (0%)
Toothache	3/235 (1.3%)		12/242 (5%)
Upper gastrointestinal haemorrhage	1/235 (0.4%)		0/242 (0%)
Vomiting projectile	0/235 (0%)		1/242 (0.4%)
General disorders
Asthenia	29/235 (12.3%)		21/242 (8.7%)
Chest pain	12/235 (5.1%)		10/242 (4.1%)
Chills	13/235 (5.5%)		17/242 (7%)
Fatigue	148/235 (63%)		156/242 (64.5%)
Mucosal inflammation	50/235 (21.3%)		52/242 (21.5%)
Oedema	11/235 (4.7%)		11/242 (4.5%)
Oedema peripheral	39/235 (16.6%)		33/242 (13.6%)
Pain	25/235 (10.6%)		17/242 (7%)
Pyrexia	43/235 (18.3%)		40/242 (16.5%)
Adverse drug reaction	3/235 (1.3%)		0/242 (0%)
Application site irritation	0/235 (0%)		1/242 (0.4%)
Atrophy	0/235 (0%)		1/242 (0.4%)
Axillary pain	2/235 (0.9%)		1/242 (0.4%)
Catheter site erythema	1/235 (0.4%)		1/242 (0.4%)
Catheter site haematoma	1/235 (0.4%)		1/242 (0.4%)
Catheter site inflammation	1/235 (0.4%)		1/242 (0.4%)
Catheter site pain	4/235 (1.7%)		4/242 (1.7%)
Catheter site rash	0/235 (0%)		1/242 (0.4%)
Catheter site swelling	0/235 (0%)		1/242 (0.4%)
Chest discomfort	3/235 (1.3%)		4/242 (1.7%)
Cyst	0/235 (0%)		2/242 (0.8%)
Device malfunction	0/235 (0%)		1/242 (0.4%)
Device occlusion	1/235 (0.4%)		3/242 (1.2%)
Disease progression	0/235 (0%)		3/242 (1.2%)
Early satiety	0/235 (0%)		1/242 (0.4%)
Extravasation	1/235 (0.4%)		0/242 (0%)
Face oedema	3/235 (1.3%)		3/242 (1.2%)
Feeling abnormal	1/235 (0.4%)		0/242 (0%)
Feeling cold	1/235 (0.4%)		2/242 (0.8%)
Feeling hot	1/235 (0.4%)		2/242 (0.8%)
Fibrosis	1/235 (0.4%)		0/242 (0%)
Gait disturbance	3/235 (1.3%)		8/242 (3.3%)
Generalised oedema	2/235 (0.9%)		2/242 (0.8%)
Gravitational oedema	0/235 (0%)		1/242 (0.4%)
Hypothermia	3/235 (1.3%)		4/242 (1.7%)
Ill-defined disorder	2/235 (0.9%)		1/242 (0.4%)
Impaired healing	2/235 (0.9%)		1/242 (0.4%)
Influenza like illness	2/235 (0.9%)		9/242 (3.7%)
Infusion site extravasation	0/235 (0%)		1/242 (0.4%)
Infusion site haematoma	1/235 (0.4%)		1/242 (0.4%)
Infusion site pain	1/235 (0.4%)		0/242 (0%)
Infusion site reaction	1/235 (0.4%)		0/242 (0%)
Injection site haematoma	0/235 (0%)		1/242 (0.4%)
Injection site reaction	2/235 (0.9%)		1/242 (0.4%)
Irritability	1/235 (0.4%)		3/242 (1.2%)
Local swelling	2/235 (0.9%)		0/242 (0%)
Localised oedema	1/235 (0.4%)		1/242 (0.4%)
Malaise	3/235 (1.3%)		5/242 (2.1%)
Medical device complication	0/235 (0%)		1/242 (0.4%)
Mucosal haemorrhage	0/235 (0%)		3/242 (1.2%)
Mucosal hyperaemia	0/235 (0%)		1/242 (0.4%)
Nodule	1/235 (0.4%)		0/242 (0%)
Non-cardiac chest pain	3/235 (1.3%)		2/242 (0.8%)
Temperature intolerance	1/235 (0.4%)		0/242 (0%)
Tenderness	0/235 (0%)		1/242 (0.4%)
Thirst	1/235 (0.4%)		0/242 (0%)
Thrombosis in device	5/235 (2.1%)		3/242 (1.2%)
Ulcer	0/235 (0%)		1/242 (0.4%)
Hepatobiliary disorders
Cholecystitis	0/235 (0%)		1/242 (0.4%)
Cholelithiasis	0/235 (0%)		1/242 (0.4%)
Gallbladder fistula	1/235 (0.4%)		0/242 (0%)
Gallbladder pain	1/235 (0.4%)		0/242 (0%)
Hepatic failure	1/235 (0.4%)		0/242 (0%)
Hepatic pain	1/235 (0.4%)		0/242 (0%)
Hepatic vein thrombosis	0/235 (0%)		1/242 (0.4%)
Hepatomegaly	1/235 (0.4%)		1/242 (0.4%)
Hyperbilirubinaemia	7/235 (3%)		3/242 (1.2%)
Hypertransaminasaemia	1/235 (0.4%)		1/242 (0.4%)
Jaundice	1/235 (0.4%)		0/242 (0%)
Portal hypertension	0/235 (0%)		1/242 (0.4%)
Immune system disorders
Contrast media allergy	0/235 (0%)		1/242 (0.4%)
Drug hypersensitivity	4/235 (1.7%)		4/242 (1.7%)
Hypersensitivity	7/235 (3%)		7/242 (2.9%)
Iodine allergy	0/235 (0%)		1/242 (0.4%)
Multiple allergies	1/235 (0.4%)		1/242 (0.4%)
Seasonal allergy	6/235 (2.6%)		6/242 (2.5%)
Infections and infestations
Sinusitis	18/235 (7.7%)		21/242 (8.7%)
Upper respiratory tract infection	20/235 (8.5%)		45/242 (18.6%)
Urinary tract infection	31/235 (13.2%)		43/242 (17.8%)
Abscess	2/235 (0.9%)		0/242 (0%)
Anal abscess	0/235 (0%)		1/242 (0.4%)
Asymptomatic bacteriuria	1/235 (0.4%)		0/242 (0%)
Bacteraemia	1/235 (0.4%)		1/242 (0.4%)
Breast infection	2/235 (0.9%)		0/242 (0%)
Bronchitis	7/235 (3%)		5/242 (2.1%)
Candidiasis	7/235 (3%)		4/242 (1.7%)
Catheter site cellulitis	0/235 (0%)		1/242 (0.4%)
Catheter site infection	4/235 (1.7%)		6/242 (2.5%)
Cellulitis	7/235 (3%)		7/242 (2.9%)
Cellulitis streptococcal	0/235 (0%)		1/242 (0.4%)
Chest wall abscess	1/235 (0.4%)		0/242 (0%)
Chronic sinusitis	0/235 (0%)		1/242 (0.4%)
Clostridial infection	0/235 (0%)		1/242 (0.4%)
Clostridium difficile colitis	2/235 (0.9%)		2/242 (0.8%)
Cystitis	5/235 (2.1%)		5/242 (2.1%)
Device related infection	4/235 (1.7%)		5/242 (2.1%)
Diverticulitis	1/235 (0.4%)		0/242 (0%)
Ear infection	2/235 (0.9%)		2/242 (0.8%)
Escherichia sepsis	0/235 (0%)		1/242 (0.4%)
Eye infection	2/235 (0.9%)		5/242 (2.1%)
Folliculitis	4/235 (1.7%)		8/242 (3.3%)
Fungal infection	4/235 (1.7%)		5/242 (2.1%)
Fungal skin infection	2/235 (0.9%)		2/242 (0.8%)
Furuncle	2/235 (0.9%)		2/242 (0.8%)
Gastroenteritis	0/235 (0%)		1/242 (0.4%)
Genital herpes	1/235 (0.4%)		0/242 (0%)
Gingival infection	0/235 (0%)		1/242 (0.4%)
Groin abscess	1/235 (0.4%)		0/242 (0%)
Groin infection	0/235 (0%)		1/242 (0.4%)
Hepatitis C	1/235 (0.4%)		0/242 (0%)
Herpes simplex	0/235 (0%)		1/242 (0.4%)
Herpes zoster	1/235 (0.4%)		4/242 (1.7%)
Hordeolum	1/235 (0.4%)		2/242 (0.8%)
Incision site infection	1/235 (0.4%)		1/242 (0.4%)
Infection	3/235 (1.3%)		3/242 (1.2%)
Influenza	4/235 (1.7%)		3/242 (1.2%)
Labyrinthitis	0/235 (0%)		1/242 (0.4%)
Laryngitis	2/235 (0.9%)		5/242 (2.1%)
Localised infection	2/235 (0.9%)		5/242 (2.1%)
Lower respiratory tract infection	0/235 (0%)		2/242 (0.8%)
Lung infection	2/235 (0.9%)		0/242 (0%)
Mucocutaneous candidiasis	0/235 (0%)		1/242 (0.4%)
Nail bed infection	1/235 (0.4%)		2/242 (0.8%)
Nail bed infection bacterial	0/235 (0%)		1/242 (0.4%)
Nail infection	0/235 (0%)		4/242 (1.7%)
Nasopharyngitis	3/235 (1.3%)		6/242 (2.5%)
Oesophageal candidiasis	0/235 (0%)		1/242 (0.4%)
Onychomycosis	1/235 (0.4%)		4/242 (1.7%)
Oral candidiasis	2/235 (0.9%)		1/242 (0.4%)
Oral herpes	6/235 (2.6%)		7/242 (2.9%)
Oral infection	1/235 (0.4%)		1/242 (0.4%)
Osteomyelitis	1/235 (0.4%)		0/242 (0%)
Otitis media	0/235 (0%)		1/242 (0.4%)
Paronychia	2/235 (0.9%)		1/242 (0.4%)
Parotitis	0/235 (0%)		1/242 (0.4%)
Pelvic abscess	0/235 (0%)		1/242 (0.4%)
Perirectal abscess	1/235 (0.4%)		1/242 (0.4%)
Pharyngitis	4/235 (1.7%)		2/242 (0.8%)
Pneumonia	4/235 (1.7%)		1/242 (0.4%)
Rash pustular	2/235 (0.9%)		3/242 (1.2%)
Respiratory tract infection	0/235 (0%)		3/242 (1.2%)
Rhinitis	3/235 (1.3%)		8/242 (3.3%)
Sepsis	0/235 (0%)		1/242 (0.4%)
Sialoadenitis	0/235 (0%)		1/242 (0.4%)
Skin infection	3/235 (1.3%)		1/242 (0.4%)
Soft tissue infection	1/235 (0.4%)		0/242 (0%)
Staphylococcal infection	1/235 (0.4%)		1/242 (0.4%)
Staphylococcal osteomyelitis	0/235 (0%)		1/242 (0.4%)
Subcutaneous abscess	4/235 (1.7%)		2/242 (0.8%)
Tonsillitis	1/235 (0.4%)		0/242 (0%)
Tooth abscess	0/235 (0%)		5/242 (2.1%)
Tooth infection	2/235 (0.9%)		5/242 (2.1%)
Viral infection	0/235 (0%)		3/242 (1.2%)
Viral upper respiratory tract infection	1/235 (0.4%)		1/242 (0.4%)
Vulvovaginal candidiasis	0/235 (0%)		1/242 (0.4%)
Vulvovaginal mycotic infection	2/235 (0.9%)		3/242 (1.2%)
Vulvovaginitis	0/235 (0%)		1/242 (0.4%)
Wound infection	0/235 (0%)		1/242 (0.4%)
Wound infection staphylococcal	0/235 (0%)		1/242 (0.4%)
Injury, poisoning and procedural complications
Accidental overdose	1/235 (0.4%)		0/242 (0%)
Burns second degree	0/235 (0%)		1/242 (0.4%)
Contusion	9/235 (3.8%)		8/242 (3.3%)
Excoriation	2/235 (0.9%)		2/242 (0.8%)
Eye injury	0/235 (0%)		1/242 (0.4%)
Eye penetration	1/235 (0.4%)		0/242 (0%)
Fall	7/235 (3%)		6/242 (2.5%)
Foot fracture	1/235 (0.4%)		2/242 (0.8%)
Gastroenteritis radiation	1/235 (0.4%)		0/242 (0%)
Humerus fracture	0/235 (0%)		1/242 (0.4%)
Infusion related reaction	2/235 (0.9%)		2/242 (0.8%)
Joint disclocation	1/235 (0.4%)		0/242 (0%)
Joint injury	0/235 (0%)		1/242 (0.4%)
Joint sprain	1/235 (0.4%)		0/242 (0%)
Laceration	1/235 (0.4%)		1/242 (0.4%)
Limb injury	0/235 (0%)		1/242 (0.4%)
Muscle strain	0/235 (0%)		2/242 (0.8%)
Open wound	0/235 (0%)		1/242 (0.4%)
Procedural pain	3/235 (1.3%)		2/242 (0.8%)
Radiation skin injury	0/235 (0%)		1/242 (0.4%)
Radius fracture	0/235 (0%)		1/242 (0.4%)
Rib fracture	0/235 (0%)		2/242 (0.8%)
Road traffic accident	1/235 (0.4%)		0/242 (0%)
Scapula fracture	0/235 (0%)		1/242 (0.4%)
Skeletal injury	0/235 (0%)		1/242 (0.4%)
Spinal compression fracture	1/235 (0.4%)		0/242 (0%)
Sunburn	1/235 (0.4%)		1/242 (0.4%)
Tendon rupture	0/235 (0%)		1/242 (0.4%)
Thermal burn	2/235 (0.9%)		2/242 (0.8%)
Tooth fracture	0/235 (0%)		1/242 (0.4%)
Toxicity to various agents	1/235 (0.4%)		1/242 (0.4%)
Vitreous injury	0/235 (0%)		1/242 (0.4%)
Wound	2/235 (0.9%)		4/242 (1.7%)
Wound complication	3/235 (1.3%)		3/242 (1.2%)
Wound dehiscence	0/235 (0%)		1/242 (0.4%)
Wrist fracture	1/235 (0.4%)		0/242 (0%)
Investigations
Alanine aminotransferase increased	29/235 (12.3%)		12/242 (5%)
Aspartate aminotransferase increased	26/235 (11.1%)		16/242 (6.6%)
Blood alkaline phosphatase increased	21/235 (8.9%)		11/242 (4.5%)
Weight decreased	32/235 (13.6%)		30/242 (12.4%)
Bacterial test positive	1/235 (0.4%)		0/242 (0%)
Blood albumin decreased	2/235 (0.9%)		1/242 (0.4%)
Blood amylase increased	0/235 (0%)		1/242 (0.4%)
Blood bicarbonate decreased	0/235 (0%)		1/242 (0.4%)
Blood bilirubin increased	4/235 (1.7%)		3/242 (1.2%)
Blood chloride decreased	1/235 (0.4%)		1/242 (0.4%)
Blood cholesterol increased	1/235 (0.4%)		1/242 (0.4%)
Blood creatine increased	0/235 (0%)		1/242 (0.4%)
Blood creatinine decreased	1/235 (0.4%)		0/242 (0%)
Blood creatinine increased	3/235 (1.3%)		10/242 (4.1%)
Blood glucose decreased	1/235 (0.4%)		0/242 (0%)
Blood glucose increased	5/235 (2.1%)		1/242 (0.4%)
Blood homocysteine increased	1/235 (0.4%)		1/242 (0.4%)
Blood lactate dehydrogenase increased	2/235 (0.9%)		0/242 (0%)
Blood magnesium decreased	3/235 (1.3%)		4/242 (1.7%)
Blood magnesium increased	1/235 (0.4%)		0/242 (0%)
Blood parathyroid hormone increased	1/235 (0.4%)		0/242 (0%)
Blood phosphorus decreased	1/235 (0.4%)		1/242 (0.4%)
Blood phosphorus increased	1/235 (0.4%)		0/242 (0%)
Blood potassium decreased	3/235 (1.3%)		1/242 (0.4%)
Blood potassium increased	0/235 (0%)		1/242 (0.4%)
Blood pressure increased	1/235 (0.4%)		5/242 (2.1%)
Blood sodium decreased	2/235 (0.9%)		1/242 (0.4%)
Blood thyroid stimulating hormone decreased	1/235 (0.4%)		0/242 (0%)
Blood thyroid stimulating hormone increased	2/235 (0.9%)		1/242 (0.4%)
Blood triglycerides increased	0/235 (0%)		2/242 (0.8%)
Blood urea increased	0/235 (0%)		3/242 (1.2%)
Blood uric acid increased	0/235 (0%)		2/242 (0.8%)
Blood urine	1/235 (0.4%)		0/242 (0%)
Body temperature increased	1/235 (0.4%)		0/242 (0%)
Breath sounds abnormal	5/235 (2.1%)		1/242 (0.4%)
Cardiac murmur	0/235 (0%)		2/242 (0.8%)
Ejection fraction decreased	5/235 (2.1%)		8/242 (3.3%)
Electrocardiogram QT prolonged	0/235 (0%)		2/242 (0.8%)
Electrocardiogram T wave inversion	1/235 (0.4%)		0/242 (0%)
Electrocardiogram abnormal	1/235 (0.4%)		0/242 (0%)
Fungal test positive	0/235 (0%)		1/242 (0.4%)
Gallop rhythm present	0/235 (0%)		1/242 (0.4%)
Gamma-glutamyltransferase increased	0/235 (0%)		1/242 (0.4%)
Glomerular filtration rate decreased	0/235 (0%)		1/242 (0.4%)
Haematocrit decreased	1/235 (0.4%)		1/242 (0.4%)
Haemoglobin decreased	12/235 (5.1%)		15/242 (6.2%)
Haemoglobin increased	0/235 (0%)		1/242 (0.4%)
Heart rate increased	1/235 (0.4%)		1/242 (0.4%)
Heart rate irregular	1/235 (0.4%)		0/242 (0%)
International normalised ratio	1/235 (0.4%)		0/242 (0%)
International normalised ratio increased	2/235 (0.9%)		1/242 (0.4%)
Lipase increased	0/235 (0%)		1/242 (0.4%)
Lymphocyte count decreased	2/235 (0.9%)		0/242 (0%)
Neutrophil count	1/235 (0.4%)		0/242 (0%)
Neutrophil count decreased	9/235 (3.8%)		6/242 (2.5%)
Neutrophil count increased	0/235 (0%)		2/242 (0.8%)
Platelet count decreased	7/235 (3%)		2/242 (0.8%)
Platelet count increased	1/235 (0.4%)		0/242 (0%)
Protein total decreased	0/235 (0%)		1/242 (0.4%)
Protein urine present	1/235 (0.4%)		0/242 (0%)
Right ventricular systolic pressure increased	0/235 (0%)		1/242 (0.4%)
Thyroxine increased	1/235 (0.4%)		0/242 (0%)
Transaminases increased	2/235 (0.9%)		1/242 (0.4%)
Urine leukocyte esterase positive	0/235 (0%)		1/242 (0.4%)
Urine protein/creatinine ratio increased	0/235 (0%)		4/242 (1.7%)
Vitamin D decreased	1/235 (0.4%)		2/242 (0.8%)
Weight increased	7/235 (3%)		4/242 (1.7%)
White blood cell count	1/235 (0.4%)		0/242 (0%)
White blood cell count decreased	7/235 (3%)		9/242 (3.7%)
White blood cell count increased	0/235 (0%)		2/242 (0.8%)
Metabolism and nutrition disorders
Decreased appetite	71/235 (30.2%)		62/242 (25.6%)
Dehydration	31/235 (13.2%)		22/242 (9.1%)
Hyperglycaemia	26/235 (11.1%)		30/242 (12.4%)
Hypoalbuminaemia	15/235 (6.4%)		13/242 (5.4%)
Hypocalcaemia	15/235 (6.4%)		7/242 (2.9%)
Hypokalaemia	39/235 (16.6%)		27/242 (11.2%)
Hypomagnesaemia	17/235 (7.2%)		19/242 (7.9%)
Hyponatraemia	17/235 (7.2%)		9/242 (3.7%)
Diabetes mellitus	0/235 (0%)		1/242 (0.4%)
Enzyme abnormality	1/235 (0.4%)		0/242 (0%)
Failure to thrive	2/235 (0.9%)		1/242 (0.4%)
Fluid intake reduced	1/235 (0.4%)		1/242 (0.4%)
Fluid overload	1/235 (0.4%)		0/242 (0%)
Fluid retention	2/235 (0.9%)		2/242 (0.8%)
Folate deficiency	0/235 (0%)		1/242 (0.4%)
Gout	0/235 (0%)		1/242 (0.4%)
Hypercalcaemia	1/235 (0.4%)		5/242 (2.1%)
Hypercholesterolaemia	4/235 (1.7%)		2/242 (0.8%)
Hyperkalaemia	5/235 (2.1%)		5/242 (2.1%)
Hyperlipidaemia	1/235 (0.4%)		0/242 (0%)
Hypernatraemia	1/235 (0.4%)		2/242 (0.8%)
Hyperuricaemia	2/235 (0.9%)		2/242 (0.8%)
Hypoglycaemia	3/235 (1.3%)		1/242 (0.4%)
Hypophosphataemia	7/235 (3%)		2/242 (0.8%)
Hypophagia	1/235 (0.4%)		0/242 (0%)
Hypovolaemia	1/235 (0.4%)		3/242 (1.2%)
Increased appetite	1/235 (0.4%)		0/242 (0%)
Iron deficiency	0/235 (0%)		1/242 (0.4%)
Malnutrition	0/235 (0%)		1/242 (0.4%)
Vitamin B12 deficiency	2/235 (0.9%)		1/242 (0.4%)
Vitamin D deficiency	3/235 (1.3%)		2/242 (0.8%)
Musculoskeletal and connective tissue disorders
Arthralgia	45/235 (19.1%)		64/242 (26.4%)
Back pain	39/235 (16.6%)		39/242 (16.1%)
Bone pain	30/235 (12.8%)		26/242 (10.7%)
Muscle spasms	14/235 (6%)		15/242 (6.2%)
Muscular weakness	9/235 (3.8%)		17/242 (7%)
Musculoskeletal chest pain	12/235 (5.1%)		21/242 (8.7%)
Musculoskeletal pain	16/235 (6.8%)		23/242 (9.5%)
Myalgia	26/235 (11.1%)		42/242 (17.4%)
Pain in extremity	27/235 (11.5%)		54/242 (22.3%)
Arthritis	1/235 (0.4%)		2/242 (0.8%)
Arthropathy	1/235 (0.4%)		0/242 (0%)
Axillary mass	0/235 (0%)		1/242 (0.4%)
Bone cyst	0/235 (0%)		1/242 (0.4%)
Chest wall necrosis	1/235 (0.4%)		0/242 (0%)
Coccydynia	0/235 (0%)		2/242 (0.8%)
Costochondritis	0/235 (0%)		1/242 (0.4%)
Exostosis	1/235 (0.4%)		0/242 (0%)
Flank pain	2/235 (0.9%)		7/242 (2.9%)
Groin pain	0/235 (0%)		4/242 (1.7%)
Intervertebral disc disorder	0/235 (0%)		1/242 (0.4%)
Joint effusion	0/235 (0%)		1/242 (0.4%)
Joint stiffness	1/235 (0.4%)		0/242 (0%)
Joint swelling	3/235 (1.3%)		2/242 (0.8%)
Limb discomfort	2/235 (0.9%)		0/242 (0%)
Muscle twitching	0/235 (0%)		2/242 (0.8%)
Musculoskeletal discomfort	0/235 (0%)		4/242 (1.7%)
Musculoskeletal stiffness	4/235 (1.7%)		2/242 (0.8%)
Myopathy	0/235 (0%)		1/242 (0.4%)
Neck pain	3/235 (1.3%)		5/242 (2.1%)
Osteonecrosis	0/235 (0%)		1/242 (0.4%)
Osteonecrosis of jaw	1/235 (0.4%)		0/242 (0%)
Osteopenia	1/235 (0.4%)		0/242 (0%)
Pain in jaw	2/235 (0.9%)		7/242 (2.9%)
Polyarthritis	0/235 (0%)		1/242 (0.4%)
Sensation of heaviness	2/235 (0.9%)		0/242 (0%)
Trigger finger	1/235 (0.4%)		0/242 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer	0/235 (0%)		1/242 (0.4%)
Cancer pain	0/235 (0%)		1/242 (0.4%)
Haemangioma	1/235 (0.4%)		0/242 (0%)
Melanocytic naevus	0/235 (0%)		1/242 (0.4%)
Parathyroid tumour benign	1/235 (0.4%)		0/242 (0%)
Skin papilloma	1/235 (0.4%)		0/242 (0%)
Squamous cell carcinoma	1/235 (0.4%)		0/242 (0%)
Tumour pain	0/235 (0%)		1/242 (0.4%)
Nervous system disorders
Dizziness	24/235 (10.2%)		51/242 (21.1%)
Dysgeusia	62/235 (26.4%)		53/242 (21.9%)
Headache	56/235 (23.8%)		67/242 (27.7%)
Neuropathy peripheral	93/235 (39.6%)		116/242 (47.9%)
Paraesthesia	16/235 (6.8%)		18/242 (7.4%)
Peripheral sensory neuropathy	21/235 (8.9%)		32/242 (13.2%)
Ageusia	1/235 (0.4%)		1/242 (0.4%)
Amnesia	1/235 (0.4%)		2/242 (0.8%)
Aphasia	3/235 (1.3%)		1/242 (0.4%)
Aphonia	0/235 (0%)		1/242 (0.4%)
Ataxia	2/235 (0.9%)		2/242 (0.8%)
Balance disorder	0/235 (0%)		8/242 (3.3%)
Burning sensation	0/235 (0%)		2/242 (0.8%)
Cognitive disorder	1/235 (0.4%)		1/242 (0.4%)
Convulsion	0/235 (0%)		1/242 (0.4%)
Cranial nerve disorder	0/235 (0%)		1/242 (0.4%)
Disturbance in attention	0/235 (0%)		1/242 (0.4%)
Dysarthria	1/235 (0.4%)		1/242 (0.4%)
Dyskinesia	0/235 (0%)		1/242 (0.4%)
Hemiparesis	1/235 (0.4%)		1/242 (0.4%)
Hepatic encephalopathy	1/235 (0.4%)		1/242 (0.4%)
Hydrocephalus	0/235 (0%)		1/242 (0.4%)
Hyperaesthesia	3/235 (1.3%)		1/242 (0.4%)
Hypersomnia	1/235 (0.4%)		1/242 (0.4%)
Hypoaesthesia	5/235 (2.1%)		11/242 (4.5%)
Hypogeusia	1/235 (0.4%)		2/242 (0.8%)
Hyporeflexia	0/235 (0%)		1/242 (0.4%)
Lethargy	1/235 (0.4%)		2/242 (0.8%)
Memory impairment	5/235 (2.1%)		3/242 (1.2%)
Migraine	3/235 (1.3%)		3/242 (1.2%)
Nercolepsy	0/235 (0%)		1/242 (0.4%)
Neuralgia	0/235 (0%)		1/242 (0.4%)
Neurotoxicity	5/235 (2.1%)		4/242 (1.7%)
Parosmia	0/235 (0%)		1/242 (0.4%)
Partial seizures	1/235 (0.4%)		0/242 (0%)
Peripheral motor neuropathy	2/235 (0.9%)		2/242 (0.8%)
Peripheral sensorimotor neuropathy	0/235 (0%)		2/242 (0.8%)
Peroneal nerve palsy	1/235 (0.4%)		0/242 (0%)
Polyneuropathy	0/235 (0%)		1/242 (0.4%)
Presyncope	0/235 (0%)		1/242 (0.4%)
Psychomotor hyperactivity	1/235 (0.4%)		0/242 (0%)
Reflexes abnormal	1/235 (0.4%)		0/242 (0%)
Restless legs syndrome	3/235 (1.3%)		6/242 (2.5%)
Reversible ischaemic neurological deficit	1/235 (0.4%)		0/242 (0%)
Sciatica	0/235 (0%)		2/242 (0.8%)
Sensory disturbance	0/235 (0%)		1/242 (0.4%)
Sinus headache	6/235 (2.6%)		8/242 (3.3%)
Somnolence	4/235 (1.7%)		1/242 (0.4%)
Speech disorder	1/235 (0.4%)		1/242 (0.4%)
Syncope	3/235 (1.3%)		2/242 (0.8%)
Transient ischaemic attach	0/235 (0%)		1/242 (0.4%)
Tremor	5/235 (2.1%)		3/242 (1.2%)
Visual field defect	1/235 (0.4%)		0/242 (0%)
Psychiatric disorders
Anxiety	31/235 (13.2%)		23/242 (9.5%)
Depression	19/235 (8.1%)		23/242 (9.5%)
Insomnia	50/235 (21.3%)		48/242 (19.8%)
Affect lability	0/235 (0%)		1/242 (0.4%)
Agitation	1/235 (0.4%)		2/242 (0.8%)
Bipolar disorder	1/235 (0.4%)		0/242 (0%)
Confusional state	9/235 (3.8%)		9/242 (3.7%)
Depressed mood	2/235 (0.9%)		1/242 (0.4%)
Disorientation	2/235 (0.9%)		1/242 (0.4%)
Executive dysfunction	0/235 (0%)		1/242 (0.4%)
Hallucination	2/235 (0.9%)		1/242 (0.4%)
Mental status changes	6/235 (2.6%)		1/242 (0.4%)
Mood altered	2/235 (0.9%)		7/242 (2.9%)
Mood swings	1/235 (0.4%)		0/242 (0%)
Nervousness	1/235 (0.4%)		1/242 (0.4%)
Nightmare	1/235 (0.4%)		0/242 (0%)
Panic attack	0/235 (0%)		1/242 (0.4%)
Psychotic disorder	1/235 (0.4%)		0/242 (0%)
Restlessness	0/235 (0%)		2/242 (0.8%)
Stress	0/235 (0%)		2/242 (0.8%)
Renal and urinary disorders
Bladder disorder	1/235 (0.4%)		0/242 (0%)
Bladder spasm	1/235 (0.4%)		1/242 (0.4%)
Chromaturia	1/235 (0.4%)		1/242 (0.4%)
Cystitis interstitial	0/235 (0%)		1/242 (0.4%)
Dysuria	9/235 (3.8%)		7/242 (2.9%)
Haematuria	1/235 (0.4%)		7/242 (2.9%)
Haemoglobinuria	1/235 (0.4%)		0/242 (0%)
Hydronephrosis	0/235 (0%)		1/242 (0.4%)
Hypertonic bladder	0/235 (0%)		1/242 (0.4%)
Incotinence	0/235 (0%)		2/242 (0.8%)
Micturition urgency	1/235 (0.4%)		2/242 (0.8%)
Nocturia	0/235 (0%)		1/242 (0.4%)
Pollakiuria	2/235 (0.9%)		4/242 (1.7%)
Proteinuria	8/235 (3.4%)		16/242 (6.6%)
Renal failure	1/235 (0.4%)		2/242 (0.8%)
Renal failure acute	0/235 (0%)		1/242 (0.4%)
Renal pain	1/235 (0.4%)		1/242 (0.4%)
Urinary hesitation	0/235 (0%)		1/242 (0.4%)
Urinary incontinence	4/235 (1.7%)		4/242 (1.7%)
Urinary retention	0/235 (0%)		1/242 (0.4%)
Urine odour abnormal	0/235 (0%)		1/242 (0.4%)
Urogenital disorder	1/235 (0.4%)		0/242 (0%)
Reproductive system and breast disorders
Amenorrhoea	0/235 (0%)		1/242 (0.4%)
Atrophic vulvovaginitis	0/235 (0%)		1/242 (0.4%)
Bartholin's cyst	1/235 (0.4%)		0/242 (0%)
Breast disorder	0/235 (0%)		1/242 (0.4%)
Breast induration	1/235 (0.4%)		0/242 (0%)
Breast oedema	1/235 (0.4%)		0/242 (0%)
Breast pain	6/235 (2.6%)		7/242 (2.9%)
Breast tenderness	1/235 (0.4%)		1/242 (0.4%)
Dyspareunia	0/235 (0%)		2/242 (0.8%)
Endometrial hyperplasia	0/235 (0%)		1/242 (0.4%)
Genital lesion	0/235 (0%)		1/242 (0.4%)
Genital rash	0/235 (0%)		1/242 (0.4%)
Genital tract inflammation	1/235 (0.4%)		0/242 (0%)
Metrorrhagia	1/235 (0.4%)		0/242 (0%)
Nipple pain	1/235 (0.4%)		0/242 (0%)
Oligomenorrhoea	0/235 (0%)		1/242 (0.4%)
Pelvic pain	0/235 (0%)		2/242 (0.8%)
Uterine polyp	1/235 (0.4%)		0/242 (0%)
Vaginal discharge	2/235 (0.9%)		1/242 (0.4%)
Vaginal exfoliation	0/235 (0%)		1/242 (0.4%)
Vaginal haemorrhage	4/235 (1.7%)		4/242 (1.7%)
Vaginal inflammation	1/235 (0.4%)		0/242 (0%)
Vaginal laceration	2/235 (0.9%)		0/242 (0%)
Vaginal mucosal blistering	0/235 (0%)		1/242 (0.4%)
Vulvovaginal discomfort	1/235 (0.4%)		0/242 (0%)
Vulvovaginal pain	1/235 (0.4%)		0/242 (0%)
Vulvovaginal pruritus	0/235 (0%)		1/242 (0.4%)
Respiratory, thoracic and mediastinal disorders
Cough	46/235 (19.6%)		72/242 (29.8%)
Dysphonia	7/235 (3%)		20/242 (8.3%)
Dyspnoea	55/235 (23.4%)		63/242 (26%)
Epistaxis	69/235 (29.4%)		100/242 (41.3%)
Nasal congestion	12/235 (5.1%)		18/242 (7.4%)
Oropharyngeal pain	21/235 (8.9%)		32/242 (13.2%)
Rhinorrhoea	1/235 (0.4%)		16/242 (6.6%)
Allergic sinusitis	0/235 (0%)		2/242 (0.8%)
Asthma	0/235 (0%)		1/242 (0.4%)
Bronchial hyperreactivity	0/235 (0%)		1/242 (0.4%)
Chronic obstructive pulmonary disease	1/235 (0.4%)		1/242 (0.4%)
Diaphragmatic disorder	0/235 (0%)		1/242 (0.4%)
Dyspnoea exertional	5/235 (2.1%)		7/242 (2.9%)
Emphysema	1/235 (0.4%)		0/242 (0%)
Haemoptysis	4/235 (1.7%)		4/242 (1.7%)
Hypercapnia	0/235 (0%)		1/242 (0.4%)
Hypoxia	1/235 (0.4%)		1/242 (0.4%)
Increased bronchial secretion	1/235 (0.4%)		0/242 (0%)
Lung infiltration	0/235 (0%)		1/242 (0.4%)
Nasal discomfort	0/235 (0%)		2/242 (0.8%)
Nasal disorder	3/235 (1.3%)		3/242 (1.2%)
Nasal dryness	2/235 (0.9%)		3/242 (1.2%)
Nasal obstruction	1/235 (0.4%)		0/242 (0%)
Nasal ulcer	0/235 (0%)		1/242 (0.4%)
Oropharyngeal discomfort	1/235 (0.4%)		0/242 (0%)
Painful respiration	1/235 (0.4%)		1/242 (0.4%)
Paranasal sinus discomfort	1/235 (0.4%)		0/242 (0%)
Paranasal sinus hypersecretion	1/235 (0.4%)		2/242 (0.8%)
Pharyngeal erythema	0/235 (0%)		1/242 (0.4%)
Pharyngeal inflammation	1/235 (0.4%)		1/242 (0.4%)
Pleural effusion	4/235 (1.7%)		7/242 (2.9%)
Pleuritic pain	1/235 (0.4%)		2/242 (0.8%)
Pneumonitis	0/235 (0%)		3/242 (1.2%)
Productive cough	4/235 (1.7%)		10/242 (4.1%)
Pulmonary congestion	0/235 (0%)		3/242 (1.2%)
Pulmonary embolism	5/235 (2.1%)		3/242 (1.2%)
Pulmonary hypertension	0/235 (0%)		1/242 (0.4%)
Pulmonary oedema	1/235 (0.4%)		0/242 (0%)
Rales	1/235 (0.4%)		0/242 (0%)
Respiratory disorder	0/235 (0%)		3/242 (1.2%)
Respiratory tract congestion	3/235 (1.3%)		6/242 (2.5%)
Rhinalgia	1/235 (0.4%)		1/242 (0.4%)
Rhinitis allergic	2/235 (0.9%)		10/242 (4.1%)
Rhinitis seasonal	0/235 (0%)		1/242 (0.4%)
Rhonchi	1/235 (0.4%)		0/242 (0%)
Sinus congestion	9/235 (3.8%)		13/242 (5.4%)
Sinus disorder	0/235 (0%)		2/242 (0.8%)
Sputum discoloured	1/235 (0.4%)		0/242 (0%)
Throat irritation	4/235 (1.7%)		0/242 (0%)
Throat tightness	1/235 (0.4%)		0/242 (0%)
Upper respiratory tract congestion	0/235 (0%)		1/242 (0.4%)
Upper-airway cough syndrome	1/235 (0.4%)		5/242 (2.1%)
Wheezing	3/235 (1.3%)		5/242 (2.1%)
Skin and subcutaneous tissue disorders
Alopecia	116/235 (49.4%)		142/242 (58.7%)
Dry skin	25/235 (10.6%)		9/242 (3.7%)
Erythema	14/235 (6%)		10/242 (4.1%)
Nail disorder	12/235 (5.1%)		50/242 (20.7%)
Palmar-plantar erythrodysaesthesia syndrome	29/235 (12.3%)		4/242 (1.7%)
Pruritus	18/235 (7.7%)		21/242 (8.7%)
Rash	66/235 (28.1%)		60/242 (24.8%)
Acne	2/235 (0.9%)		8/242 (3.3%)
Actinic keratosis	0/235 (0%)		1/242 (0.4%)
Blister	2/235 (0.9%)		5/242 (2.1%)
Cold sweat	0/235 (0%)		1/242 (0.4%)
Decubitus ulcer	3/235 (1.3%)		2/242 (0.8%)
Dermal cyst	0/235 (0%)		2/242 (0.8%)
Dermatitis	7/235 (3%)		6/242 (2.5%)
Dermatitis acneiform	3/235 (1.3%)		5/242 (2.1%)
Dermatitis allergic	1/235 (0.4%)		2/242 (0.8%)
Dermatitis contact	1/235 (0.4%)		2/242 (0.8%)
Dermatitis exfoliative	0/235 (0%)		1/242 (0.4%)
Ecchymosis	2/235 (0.9%)		1/242 (0.4%)
Eczema	2/235 (0.9%)		3/242 (1.2%)
Erythema nodosum	1/235 (0.4%)		0/242 (0%)
Exfoliative rash	2/235 (0.9%)		1/242 (0.4%)
Hair colour changes	2/235 (0.9%)		0/242 (0%)
Heat rash	0/235 (0%)		1/242 (0.4%)
Hidradenitis	1/235 (0.4%)		0/242 (0%)
Hyperhidrosis	4/235 (1.7%)		6/242 (2.5%)
Hyperkeratosis	1/235 (0.4%)		1/242 (0.4%)
Hypoaesthesia facial	2/235 (0.9%)		3/242 (1.2%)
Increased tendency to bruise	0/235 (0%)		1/242 (0.4%)
Leukoplakia	1/235 (0.4%)		0/242 (0%)
Nail bed disorder	0/235 (0%)		1/242 (0.4%)
Nail discolouration	10/235 (4.3%)		7/242 (2.9%)
Nail toxicity	1/235 (0.4%)		0/242 (0%)
Night sweats	5/235 (2.1%)		6/242 (2.5%)
Nipple ulceration	1/235 (0.4%)		0/242 (0%)
Onychalgia	0/235 (0%)		7/242 (2.9%)
Onychoclasis	1/235 (0.4%)		3/242 (1.2%)
Onycholysis	2/235 (0.9%)		5/242 (2.1%)
Onychomadesis	0/235 (0%)		2/242 (0.8%)
Pain of skin	0/235 (0%)		2/242 (0.8%)
Palmar erythema	2/235 (0.9%)		0/242 (0%)
Panniculitis	1/235 (0.4%)		0/242 (0%)
Papule	1/235 (0.4%)		1/242 (0.4%)
Petechiae	1/235 (0.4%)		1/242 (0.4%)
Pigmentation disorder	0/235 (0%)		1/242 (0.4%)
Prurtitus generalised	2/235 (0.9%)		0/242 (0%)
Psoriasis	1/235 (0.4%)		1/242 (0.4%)
Purpura senile	0/235 (0%)		1/242 (0.4%)
Rash erythematous	2/235 (0.9%)		3/242 (1.2%)
Rash follicular	0/235 (0%)		1/242 (0.4%)
Rash generalised	0/235 (0%)		1/242 (0.4%)
Rash macular	2/235 (0.9%)		3/242 (1.2%)
Rash maculo-papular	4/235 (1.7%)		0/242 (0%)
Rash pruritic	4/235 (1.7%)		4/242 (1.7%)
Rosacea	1/235 (0.4%)		1/242 (0.4%)
Scab	1/235 (0.4%)		1/242 (0.4%)
Scar	0/235 (0%)		1/242 (0.4%)
Scar pain	0/235 (0%)		1/242 (0.4%)
Skin discolouration	7/235 (3%)		7/242 (2.9%)
Skin disorder	1/235 (0.4%)		2/242 (0.8%)
Skin exfoliation	7/235 (3%)		5/242 (2.1%)
Skin fissures	2/235 (0.9%)		0/242 (0%)
Skin hyperpigmentation	0/235 (0%)		7/242 (2.9%)
Skin hypertrophy	0/235 (0%)		1/242 (0.4%)
Skin hypopigmentation	2/235 (0.9%)		0/242 (0%)
Skin irritation	1/235 (0.4%)		2/242 (0.8%)
Skin lesion	5/235 (2.1%)		2/242 (0.8%)
Skin reaction	2/235 (0.9%)		0/242 (0%)
Skin tightness	1/235 (0.4%)		1/242 (0.4%)
Skin ulcer	3/235 (1.3%)		3/242 (1.2%)
Swelling face	3/235 (1.3%)		4/242 (1.7%)
Urticaria	3/235 (1.3%)		3/242 (1.2%)
Yellow skin	1/235 (0.4%)		0/242 (0%)
Surgical and medical procedures
Mastectomy	1/235 (0.4%)		0/242 (0%)
Vascular disorders
Flushing	15/235 (6.4%)		12/242 (5%)
Hot flush	20/235 (8.5%)		20/242 (8.3%)
Hypertension	52/235 (22.1%)		77/242 (31.8%)
Hypotension	15/235 (6.4%)		9/242 (3.7%)
Aortic stenosis	0/235 (0%)		1/242 (0.4%)
Atteriosclerosis	1/235 (0.4%)		0/242 (0%)
Deep vein thrombosis	2/235 (0.9%)		6/242 (2.5%)
Haematoma	1/235 (0.4%)		1/242 (0.4%)
Haemorrhage	0/235 (0%)		2/242 (0.8%)
Infarction	1/235 (0.4%)		0/242 (0%)
Jugular vein thrombosis	1/235 (0.4%)		0/242 (0%)
Lymphoedema	7/235 (3%)		14/242 (5.8%)
Orthostatic hypotension	2/235 (0.9%)		1/242 (0.4%)
Pallor	1/235 (0.4%)		2/242 (0.8%)
Peripheral coldness	0/235 (0%)		1/242 (0.4%)
Phlebitis	0/235 (0%)		2/242 (0.8%)
Phlebitis superficial	0/235 (0%)		1/242 (0.4%)
Poor peripheral circulation	0/235 (0%)		1/242 (0.4%)
Subclavian vein thrombosis	0/235 (0%)		1/242 (0.4%)
Superior vena cava syndrome	0/235 (0%)		1/242 (0.4%)
Systolic hypertension	1/235 (0.4%)		0/242 (0%)
Thrombosis	0/235 (0%)		2/242 (0.8%)
Vasodilatation	1/235 (0.4%)		0/242 (0%)
Venous thrombosis	0/235 (0%)		1/242 (0.4%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

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

Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.