Trial Outcomes & Findings for A Study of Ixabepilone as Second-line Therapy for Locally Advanced, Recurrent, or Metastatic Endometrial Cancer (NCT NCT00883116)

Last Updated: 2017-03-09

Results Overview

Survival was defined as the time from the date of randomization until the date of death. If the patient did not die, OS was censored on the last date he or she was known to be alive.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

551 participants

Primary outcome timeframe

Date of randomization to date of death or last date censored to up to approximately 26 months

Results posted on

2017-03-09

Participant Flow

551 participants enrolled. 496 randomized (248 ixabepilone, 248 control); 487 received treatment (248 ixabepilone, 239 to control). Reasons not treated include 1 no longer met study criteria, 1 withdrew consent, 1 condition worsened, and 6 non-specified.

Participant milestones

Participant milestones
Measure	Ixabepilone, 40 mg/m^2, IV Participants received ixabepilone, 40 mg/m\^2, given intravenously (IV) over 3 hours every 21 days until unacceptable toxicity or disease progression	Control Chemotherapy Participants received either paclitaxel, 175 mg/m\^2 given IV over 3 hours, or per institutional guidelines but not exceeding 3 hours, every 21 days until disease progression or unacceptable toxicity or doxorubicin, 60 mg/m\^2 given IV per institutional guidelines every 21 days, depending on the prior therapy received, until disease progression, unacceptable toxicity, or cumulative dose of 500 mg/m\^2.
Overall Study STARTED	248	248
Overall Study Received Treatment	248	239
Overall Study COMPLETED	39	29
Overall Study NOT COMPLETED	209	219

Reasons for withdrawal

Reasons for withdrawal
Measure	Ixabepilone, 40 mg/m^2, IV Participants received ixabepilone, 40 mg/m\^2, given intravenously (IV) over 3 hours every 21 days until unacceptable toxicity or disease progression	Control Chemotherapy Participants received either paclitaxel, 175 mg/m\^2 given IV over 3 hours, or per institutional guidelines but not exceeding 3 hours, every 21 days until disease progression or unacceptable toxicity or doxorubicin, 60 mg/m\^2 given IV per institutional guidelines every 21 days, depending on the prior therapy received, until disease progression, unacceptable toxicity, or cumulative dose of 500 mg/m\^2.
Overall Study Adverse event unrelated to study drug	5	10
Overall Study Death	6	2
Overall Study Disease progression	130	128
Overall Study Lost to Follow-up	0	1
Overall Study Maximum clinical benefit	13	46
Overall Study Not identified	3	6
Overall Study Study drug toxicity	36	16
Overall Study Withdrawal by Subject	14	8
Overall Study No longer meets study criteria	2	2

Baseline Characteristics

A Study of Ixabepilone as Second-line Therapy for Locally Advanced, Recurrent, or Metastatic Endometrial Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ixabepilone, 40 mg/m^2, IV n=248 Participants Participants received ixabepilone, 40 mg/m\^2, given intravenously (IV) over 3 hours every 21 days until unacceptable toxicity or disease progression	Control Chemotherapy n=248 Participants Participants received either paclitaxel, 175 mg/m\^2 given IV over 3 hours, or per institutional guidelines but not exceeding 3 hours, every 21 days until disease progression or unacceptable toxicity or doxorubicin, 60 mg/m\^2 given IV per institutional guidelines every 21 days, depending on the prior therapy received, until disease progression, unacceptable toxicity, or cumulative dose of 500 mg/m\^2.	Total n=496 Participants Total of all reporting groups
Age, Continuous	64.0 Years n=5 Participants	64.0 Years n=7 Participants	64.0 Years n=5 Participants
Age, Customized Younger than 65 years	126 Participants n=5 Participants	139 Participants n=7 Participants	265 Participants n=5 Participants
Age, Customized 65 years and older	122 Participants n=5 Participants	109 Participants n=7 Participants	231 Participants n=5 Participants
Age, Customized Younger than 50 years	14 Participants n=5 Participants	18 Participants n=7 Participants	32 Participants n=5 Participants
Age, Customized 50 years and older	234 Participants n=5 Participants	230 Participants n=7 Participants	464 Participants n=5 Participants
Sex: Female, Male Female	248 Participants n=5 Participants	248 Participants n=7 Participants	496 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized White	215 Participants n=5 Participants	213 Participants n=7 Participants	428 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	12 Participants n=5 Participants	18 Participants n=7 Participants	30 Participants n=5 Participants
Race/Ethnicity, Customized Asian	6 Participants n=5 Participants	5 Participants n=7 Participants	11 Participants n=5 Participants
Race/Ethnicity, Customized Other	12 Participants n=5 Participants	12 Participants n=7 Participants	24 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	3 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants
Karnofsky Performance Scale Index Status 100	86 Participants n=5 Participants	86 Participants n=7 Participants	172 Participants n=5 Participants
Karnofsky Performance Scale Index Status 90	95 Participants n=5 Participants	79 Participants n=7 Participants	174 Participants n=5 Participants
Karnofsky Performance Scale Index Status 80	48 Participants n=5 Participants	64 Participants n=7 Participants	112 Participants n=5 Participants
Karnofsky Performance Scale Index Status 70	19 Participants n=5 Participants	16 Participants n=7 Participants	35 Participants n=5 Participants
Karnofsky Performance Scale Index Status <70	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Karnofsky Performance Scale Index Status Not reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: Date of randomization to date of death or last date censored to up to approximately 26 months

Population: All randomized participants

Survival was defined as the time from the date of randomization until the date of death. If the patient did not die, OS was censored on the last date he or she was known to be alive.

Outcome measures

Outcome measures
Measure	Ixabepilone, 40 mg/m^2, Intravenously (IV) n=248 Participants Participants received ixabepilone, 40 mg/m\^2, given IV over 3 hours every 21 days until unacceptable toxicity or disease progression	Control With Chemotherapy (Paclitaxel or Doxorubicin) n=248 Participants Participants received paclitaxel, 175 mg/m\^2, given IV over 3 hours, or per institutional guidelines but not exceeding 3 hours, every 21 days until disease progression or unacceptable toxicity or doxorubicin, 60 mg/m\^2, given IV per institutional guidelines every 21 days, depending on the prior therapy received, until disease progression, unacceptable toxicity, or cumulative dose of 500 mg/m\^2.
Overall Survival (OS)	10.9 Months Interval 8.5 to 12.7	12.3 Months Interval 10.7 to 15.4

SECONDARY outcome

Timeframe: Date of randomization to date of disease progression or death (or date of last tumor assessment for those who did not die or progress) up to approximately 22 months

Population: All participants with measurable disease at randomization

Progression-free survival was defined as the time from randomization to the date of documented disease progression. Patients who died without a reported prior progression were considered to have progressed on the date of their death. Those who did not progress or die were censored on the date of their last tumor assessment. Participants who did not have any on-study tumor assessments were censored on the date they were randomized. Measurable disease was present if the patient had 1 or more measurable lesions.

Outcome measures

Outcome measures
Measure	Ixabepilone, 40 mg/m^2, Intravenously (IV) n=223 Participants Participants received ixabepilone, 40 mg/m\^2, given IV over 3 hours every 21 days until unacceptable toxicity or disease progression	Control With Chemotherapy (Paclitaxel or Doxorubicin) n=223 Participants Participants received paclitaxel, 175 mg/m\^2, given IV over 3 hours, or per institutional guidelines but not exceeding 3 hours, every 21 days until disease progression or unacceptable toxicity or doxorubicin, 60 mg/m\^2, given IV per institutional guidelines every 21 days, depending on the prior therapy received, until disease progression, unacceptable toxicity, or cumulative dose of 500 mg/m\^2.
Progression-free Survival	3.4 Months Interval 2.8 to 4.2	4.0 Months Interval 2.7 to 4.3

SECONDARY outcome

Timeframe: Date of randomization and every 6 weeks to end of treatment (9 cycles, or approximately Day 189)

Population: All randomized participants with measurable disease

Best overall response rate was defined as the number of participants whose best response was either partial response (PR) or complete response (CR) divided by the number of participants in the treatment group. Overall tumor response was based on an integration of the evaluation of target, nontarget, and new lesions. CR=Disappearance of all clinical and radiologic evidence of target lesions. PR=At least 30% reduction in the sum of diameters of all target lesions; taking as reference the baseline study measurement. Changes in tumor measurements need not be confirmed by repeat measurements performed after the criteria for response were first met.

Outcome measures

Outcome measures
Measure	Ixabepilone, 40 mg/m^2, Intravenously (IV) n=223 Participants Participants received ixabepilone, 40 mg/m\^2, given IV over 3 hours every 21 days until unacceptable toxicity or disease progression	Control With Chemotherapy (Paclitaxel or Doxorubicin) n=223 Participants Participants received paclitaxel, 175 mg/m\^2, given IV over 3 hours, or per institutional guidelines but not exceeding 3 hours, every 21 days until disease progression or unacceptable toxicity or doxorubicin, 60 mg/m\^2, given IV per institutional guidelines every 21 days, depending on the prior therapy received, until disease progression, unacceptable toxicity, or cumulative dose of 500 mg/m\^2.
Best Overall Response Rate	15.2 Percentage of participants Interval 10.8 to 20.6	15.7 Percentage of participants Interval 11.2 to 21.1

SECONDARY outcome

Timeframe: From Day 1 (first dose) to 30 days past last dose (up to Day 219); 9 cycles, or 189 days + 30 days

Population: All participants who received at least 1 dose of ixabepilone

AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Related to study drug=having certain, probable, possible, or missing relationship to study drug. Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4=Life-threatening or disabling, Gr 5=Death.

Outcome measures

Outcome measures
Measure	Ixabepilone, 40 mg/m^2, Intravenously (IV) n=248 Participants Participants received ixabepilone, 40 mg/m\^2, given IV over 3 hours every 21 days until unacceptable toxicity or disease progression	Control With Chemotherapy (Paclitaxel or Doxorubicin) n=239 Participants Participants received paclitaxel, 175 mg/m\^2, given IV over 3 hours, or per institutional guidelines but not exceeding 3 hours, every 21 days until disease progression or unacceptable toxicity or doxorubicin, 60 mg/m\^2, given IV per institutional guidelines every 21 days, depending on the prior therapy received, until disease progression, unacceptable toxicity, or cumulative dose of 500 mg/m\^2.
Number of Participants With a Serious Adverse Event (SAE), an SAE Related to Study Drug, Death as Outcome, a Peripheral Neuropathy Adverse Event (AE), a Grade 3 or Higher AE, and an AE Related to Study Drug Any SAEs	89 Participants	70 Participants
Number of Participants With a Serious Adverse Event (SAE), an SAE Related to Study Drug, Death as Outcome, a Peripheral Neuropathy Adverse Event (AE), a Grade 3 or Higher AE, and an AE Related to Study Drug Any SAE related to study drug	43 Participants	29 Participants
Number of Participants With a Serious Adverse Event (SAE), an SAE Related to Study Drug, Death as Outcome, a Peripheral Neuropathy Adverse Event (AE), a Grade 3 or Higher AE, and an AE Related to Study Drug Deaths	121 Participants	95 Participants
Number of Participants With a Serious Adverse Event (SAE), an SAE Related to Study Drug, Death as Outcome, a Peripheral Neuropathy Adverse Event (AE), a Grade 3 or Higher AE, and an AE Related to Study Drug Any AE related to study drug	223 Participants	215 Participants
Number of Participants With a Serious Adverse Event (SAE), an SAE Related to Study Drug, Death as Outcome, a Peripheral Neuropathy Adverse Event (AE), a Grade 3 or Higher AE, and an AE Related to Study Drug Any AE leading to study drug discontinuation	49 Participants	37 Participants
Number of Participants With a Serious Adverse Event (SAE), an SAE Related to Study Drug, Death as Outcome, a Peripheral Neuropathy Adverse Event (AE), a Grade 3 or Higher AE, and an AE Related to Study Drug Any peripheral neuropathy AE	108 Participants	62 Participants
Number of Participants With a Serious Adverse Event (SAE), an SAE Related to Study Drug, Death as Outcome, a Peripheral Neuropathy Adverse Event (AE), a Grade 3 or Higher AE, and an AE Related to Study Drug Any Grade 3 or higher AE	160 Participants	148 Participants

Adverse Events

Ixabepilone, 40 mg/m^2, Intravenously (IV)

Serious events: 89 serious events

Other events: 233 other events

Deaths: 0 deaths

Control With Chemotherapy (Doxorubicin, 60 mg/m^2, IV)

Serious events: 59 serious events

Other events: 160 other events

Deaths: 0 deaths

Control With Chemotherapy (Paclitaxel, 175 mg/m^2, IV)

Serious events: 11 serious events

Other events: 63 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Bristol-Myers Squibb Study Director

Bristol-Myers Squibb

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	Ixabepilone, 40 mg/m^2, Intravenously (IV) n=248 participants at risk Participants received ixabepilone, 40 mg/m\^2, given intravenously (IV) over 3 hours every 21 days until unacceptable toxicity or disease progression	Control With Chemotherapy (Doxorubicin, 60 mg/m^2, IV) n=171 participants at risk Participants received doxorubicin, 60 mg/m\^2 given intravenously (IV) per institutional guidelines every 21 days, depending on the prior therapy received, until disease progression, unacceptable toxicity, or cumulative dose of 500 mg/m\^2.	Control With Chemotherapy (Paclitaxel, 175 mg/m^2, IV) n=68 participants at risk Participants received paclitaxel, 175 mg/m\^2 given IV over 3 hours, or per institutional guidelines but not exceeding 3 hours, every 21 days until disease progression or unacceptable toxicity.
Investigations Blood creatinine increased	1.2% 3/248 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	0.00% 0/171 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	0.00% 0/68 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014
General disorders Device malfunction	0.00% 0/248 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	0.00% 0/171 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	1.5% 1/68 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014
Nervous system disorders Dizziness	0.81% 2/248 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	0.00% 0/171 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	0.00% 0/68 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014
Gastrointestinal disorders Dyspepsia	0.40% 1/248 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	0.00% 0/171 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	0.00% 0/68 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014
Vascular disorders Embolism	0.40% 1/248 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	0.00% 0/171 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	0.00% 0/68 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014
Infections and infestations Endocarditis	0.40% 1/248 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	0.00% 0/171 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	1.5% 1/68 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.40% 1/248 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	0.00% 0/171 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	0.00% 0/68 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014
Renal and urinary disorders Haemorrhage urinary tract	0.00% 0/248 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	0.58% 1/171 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	0.00% 0/68 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014
Injury, poisoning and procedural complications Humerus fracture	0.40% 1/248 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	0.00% 0/171 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	0.00% 0/68 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014
Metabolism and nutrition disorders Hyperkalaemia	0.40% 1/248 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	0.00% 0/171 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	0.00% 0/68 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014
Cardiac disorders Myocardial ischaemia	0.00% 0/248 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	0.00% 0/171 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	1.5% 1/68 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014
General disorders Oedema	0.40% 1/248 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	0.00% 0/171 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	0.00% 0/68 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014
Vascular disorders Orthostatic hypotension	0.40% 1/248 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	0.00% 0/171 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	0.00% 0/68 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	1.2% 3/248 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	3.5% 6/171 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	0.00% 0/68 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014
Infections and infestations Pyelonephritis	0.00% 0/248 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	0.00% 0/171 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	1.5% 1/68 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014
Gastrointestinal disorders Rectal obstruction	0.00% 0/248 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	0.58% 1/171 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	0.00% 0/68 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.40% 1/248 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	0.00% 0/171 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	0.00% 0/68 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014
Gastrointestinal disorders Small intestinal obstruction	0.40% 1/248 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	1.2% 2/171 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	1.5% 1/68 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014
Gastrointestinal disorders Upper gastrointestinal haemorrhage	0.40% 1/248 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	0.58% 1/171 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	0.00% 0/68 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014
Renal and urinary disorders Urinary tract obstruction	0.40% 1/248 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	0.00% 0/171 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	0.00% 0/68 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014
Gastrointestinal disorders Ascites	1.2% 3/248 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	0.58% 1/171 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	0.00% 0/68 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014
Metabolism and nutrition disorders Decreased appetite	0.81% 2/248 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	0.00% 0/171 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	0.00% 0/68 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014
Renal and urinary disorders Hydronephrosis	0.81% 2/248 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	0.00% 0/171 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	0.00% 0/68 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014
Endocrine disorders Hypothyroidism	0.40% 1/248 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	0.00% 0/171 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	0.00% 0/68 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014
Gastrointestinal disorders Intestinal obstruction	0.40% 1/248 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	1.8% 3/171 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	0.00% 0/68 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014
Gastrointestinal disorders Oesophagitis	0.40% 1/248 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	0.00% 0/171 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	0.00% 0/68 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014
Musculoskeletal and connective tissue disorders Pain in extremity	0.40% 1/248 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	0.00% 0/171 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	0.00% 0/68 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014
Cardiac disorders Pericardial effusion	0.40% 1/248 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	0.00% 0/171 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	0.00% 0/68 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014
Cardiac disorders Right ventricular failure	0.40% 1/248 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	0.00% 0/171 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	0.00% 0/68 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014
Metabolism and nutrition disorders Type 2 diabetes mellitus	0.00% 0/248 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	0.00% 0/171 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	1.5% 1/68 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014
Psychiatric disorders Anxiety	0.40% 1/248 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	0.00% 0/171 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	0.00% 0/68 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014
Cardiac disorders Cardiac tamponade	0.40% 1/248 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	0.00% 0/171 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	0.00% 0/68 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014
Cardiac disorders Cardio-respiratory arrest	0.40% 1/248 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	0.00% 0/171 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	0.00% 0/68 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/248 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	3.5% 6/171 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	0.00% 0/68 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014
Reproductive system and breast disorders Dyspnoea exertional	0.00% 0/248 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	0.58% 1/171 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	0.00% 0/68 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Endometrial cancer	0.00% 0/248 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	0.00% 0/171 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	1.5% 1/68 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014
Blood and lymphatic system disorders Febrile neutropenia	4.0% 10/248 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	5.8% 10/171 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	1.5% 1/68 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014
Metabolism and nutrition disorders Hypomagnesaemia	0.40% 1/248 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	0.00% 0/171 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	0.00% 0/68 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014
Blood and lymphatic system disorders Leukopenia	1.2% 3/248 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	0.58% 1/171 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	0.00% 0/68 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to central nervous system	0.40% 1/248 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	0.00% 0/171 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	1.5% 1/68 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014

Other adverse events
Measure	Ixabepilone, 40 mg/m^2, Intravenously (IV) n=248 participants at risk Participants received ixabepilone, 40 mg/m\^2, given intravenously (IV) over 3 hours every 21 days until unacceptable toxicity or disease progression	Control With Chemotherapy (Doxorubicin, 60 mg/m^2, IV) n=171 participants at risk Participants received doxorubicin, 60 mg/m\^2 given intravenously (IV) per institutional guidelines every 21 days, depending on the prior therapy received, until disease progression, unacceptable toxicity, or cumulative dose of 500 mg/m\^2.	Control With Chemotherapy (Paclitaxel, 175 mg/m^2, IV) n=68 participants at risk Participants received paclitaxel, 175 mg/m\^2 given IV over 3 hours, or per institutional guidelines but not exceeding 3 hours, every 21 days until disease progression or unacceptable toxicity.
Nervous system disorders Dizziness	9.7% 24/248 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	5.8% 10/171 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	1.5% 1/68 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014
Gastrointestinal disorders Dyspepsia	6.9% 17/248 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	8.2% 14/171 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	0.00% 0/68 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014
Metabolism and nutrition disorders Decreased appetite	33.1% 82/248 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	26.3% 45/171 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	17.6% 12/68 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014
Nervous system disorders Hypoaesthesia	1.2% 3/248 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	0.58% 1/171 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	8.8% 6/68 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014
Nervous system disorders Neuropathy peripheral	6.9% 17/248 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	1.8% 3/171 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	7.4% 5/68 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014
Musculoskeletal and connective tissue disorders Pain in extremity	8.5% 21/248 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	7.0% 12/171 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	11.8% 8/68 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014
Psychiatric disorders Anxiety	4.4% 11/248 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	7.6% 13/171 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	1.5% 1/68 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014
Nervous system disorders Dysgeusia	9.3% 23/248 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	10.5% 18/171 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	1.5% 1/68 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014
Respiratory, thoracic and mediastinal disorders Dyspnoea	14.9% 37/248 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	19.3% 33/171 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	11.8% 8/68 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014
Metabolism and nutrition disorders Hypomagnesaemia	5.2% 13/248 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	4.1% 7/171 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	0.00% 0/68 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014
Blood and lymphatic system disorders Leukopenia	14.1% 35/248 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	14.6% 25/171 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	8.8% 6/68 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014
Respiratory, thoracic and mediastinal disorders Cough	9.3% 23/248 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	9.4% 16/171 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	7.4% 5/68 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014
Nervous system disorders Peripheral motor neuropathy	4.8% 12/248 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	1.2% 2/171 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	7.4% 5/68 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014
Investigations Haemoglobin decreased	5.2% 13/248 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	6.4% 11/171 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	4.4% 3/68 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014
Gastrointestinal disorders Nausea	47.6% 118/248 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	59.1% 101/171 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	25.0% 17/68 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014
Nervous system disorders Peripheral sensory neuropathy	31.9% 79/248 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	5.8% 10/171 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	42.6% 29/68 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014
General disorders Pyrexia	6.9% 17/248 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	12.9% 22/171 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	5.9% 4/68 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014
Reproductive system and breast disorders Vaginal haemorrhage	5.2% 13/248 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	1.2% 2/171 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	5.9% 4/68 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014
Investigations Weight increased	1.2% 3/248 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	1.2% 2/171 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	5.9% 4/68 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014
Gastrointestinal disorders Abdominal pain	18.1% 45/248 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	14.0% 24/171 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	7.4% 5/68 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014
Skin and subcutaneous tissue disorders Alopecia	41.1% 102/248 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	36.8% 63/171 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	52.9% 36/68 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014
General disorders Asthenia	15.7% 39/248 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	14.0% 24/171 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	16.2% 11/68 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014
General disorders Mucosal inflammation	8.5% 21/248 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	16.4% 28/171 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	0.00% 0/68 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014
Blood and lymphatic system disorders Neutropenia	23.4% 58/248 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	39.8% 68/171 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	16.2% 11/68 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014
Blood and lymphatic system disorders Thrombocytopenia	6.5% 16/248 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	7.0% 12/171 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	2.9% 2/68 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014
Investigations Weight decreased	19.4% 48/248 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	16.4% 28/171 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	4.4% 3/68 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014
Gastrointestinal disorders Abdominal pain upper	2.8% 7/248 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	8.2% 14/171 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	1.5% 1/68 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014
Blood and lymphatic system disorders Anaemia	25.0% 62/248 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	26.9% 46/171 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	23.5% 16/68 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014
Musculoskeletal and connective tissue disorders Arthralgia	18.5% 46/248 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	5.3% 9/171 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	32.4% 22/68 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014
Gastrointestinal disorders Constipation	31.0% 77/248 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	28.7% 49/171 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	10.3% 7/68 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014
Metabolism and nutrition disorders Dehydration	5.6% 14/248 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	4.7% 8/171 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	0.00% 0/68 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014
Gastrointestinal disorders Diarrhoea	30.6% 76/248 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	27.5% 47/171 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	11.8% 8/68 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014
Blood and lymphatic system disorders Lymphopenia	2.8% 7/248 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	6.4% 11/171 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	0.00% 0/68 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014
Musculoskeletal and connective tissue disorders Myalgia	12.9% 32/248 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	2.3% 4/171 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	25.0% 17/68 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014
Gastrointestinal disorders Stomatitis	6.5% 16/248 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	10.5% 18/171 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	1.5% 1/68 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014
Gastrointestinal disorders Vomiting	29.4% 73/248 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	28.1% 48/171 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	11.8% 8/68 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014
Musculoskeletal and connective tissue disorders Back pain	8.5% 21/248 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	8.8% 15/171 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	4.4% 3/68 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014
General disorders Fatigue	50.4% 125/248 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	51.5% 88/171 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	30.9% 21/68 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014
Nervous system disorders Headache	7.7% 19/248 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	9.4% 16/171 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	0.00% 0/68 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014
Metabolism and nutrition disorders Hypokalaemia	6.0% 15/248 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	8.2% 14/171 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014	2.9% 2/68 • Day 1 up to 30 days post last dose of study therapy, an average of 4 years Study initiated: August 2009; Study Completion: February 2014