Trial Outcomes & Findings for Paclitaxel and Carboplatin With or Without Metformin Hydrochloride in Treating Patients With Stage III, IV, or Recurrent Endometrial Cancer (NCT NCT02065687)

NCT ID: NCT02065687

Last Updated: 2021-09-30

Results Overview

Time until disease progression, death, or date of last contact. This study was originally designed as a phase II/III study. It passed the phase 2 threshold and started the phase 3; however, a phase 3 interim analysis stopped the trial for futility. Therefore, data available for Phase III may be identical to data reported for Phase II or Phase II/III combined.

• Recruitment status: UNKNOWN
• Study phase: PHASE2/PHASE3
• Target enrollment: 469 participants
• Primary outcome timeframe: From date of study entry to time of progression or death, whichever occurs first, assessed up to 5 years
• Results posted on: 2021-09-30

Participant Flow

Participant milestones

Measure	Arm I (Paclitaxel, Carboplatin, Metformin Hydrochloride) Patients receive 175 mg/m2 paclitaxel IV over 3 hours on day 1, carboplatin AUC 5 IV over 30 minutes on day 1, and 850 mg metformin hydrochloride PO BID (approximately every 10-12 hours apart) on days 1-21 (QD in course 1). Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive maintenance therapy comprising metformin hydrochloride PO BID on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Arm II (Paclitaxel, Carboplatin, Placebo) Patients receive 175 mg/m2 paclitaxel IV and carboplatin AUC 5 IV as in Arm I. Patients also receive placebo PO BID (approximately every 10-12 hours apart) on days 1-21 (QD in course 1). Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive maintenance therapy comprising placebo PO BID on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Overall Study STARTED	234	235
Overall Study COMPLETED	234	235
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Paclitaxel and Carboplatin With or Without Metformin Hydrochloride in Treating Patients With Stage III, IV, or Recurrent Endometrial Cancer

Baseline characteristics by cohort

Measure	Arm I (Paclitaxel, Carboplatin, Metformin Hydrochloride) n=234 Participants Patients receive 175 mg/m2 paclitaxel IV over 3 hours on day 1, carboplatin AUC 5 IV over 30 minutes on day 1, and 850 mg metformin hydrochloride PO BID (approximately every 10-12 hours apart) on days 1-21 (QD in course 1). Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive maintenance therapy comprising metformin hydrochloride PO BID on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Arm II (Paclitaxel, Carboplatin, Placebo) n=235 Participants Patients receive 175 mg/m2 paclitaxel IV and carboplatin AUC 5 IV as in Arm I. Patients also receive placebo PO BID (approximately every 10-12 hours apart) on days 1-21 (QD in course 1). Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive maintenance therapy comprising placebo PO BID on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Total n=469 Participants Total of all reporting groups
Age, Continuous	65 years STANDARD_DEVIATION 9 • n=5 Participants	64 years STANDARD_DEVIATION 9 • n=7 Participants	65 years STANDARD_DEVIATION 9 • n=5 Participants
Sex: Female, Male Female	234 Participants n=5 Participants	235 Participants n=7 Participants	469 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	12 Participants n=5 Participants	9 Participants n=7 Participants	21 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	214 Participants n=5 Participants	223 Participants n=7 Participants	437 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	8 Participants n=5 Participants	3 Participants n=7 Participants	11 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) Asian	10 Participants n=5 Participants	3 Participants n=7 Participants	13 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	39 Participants n=5 Participants	22 Participants n=7 Participants	61 Participants n=5 Participants
Race (NIH/OMB) White	171 Participants n=5 Participants	201 Participants n=7 Participants	372 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	10 Participants n=5 Participants	7 Participants n=7 Participants	17 Participants n=5 Participants

PRIMARY outcome

Timeframe: From date of study entry to time of progression or death, whichever occurs first, assessed up to 5 years

Population: All patients

Time until disease progression, death, or date of last contact. This study was originally designed as a phase II/III study. It passed the phase 2 threshold and started the phase 3; however, a phase 3 interim analysis stopped the trial for futility. Therefore, data available for Phase III may be identical to data reported for Phase II or Phase II/III combined.

Outcome measures

Measure	Arm I (Paclitaxel, Carboplatin, Metformin Hydrochloride) n=234 Participants Patients receive 175 mg/m2 paclitaxel IV over 3 hours on day 1, carboplatin AUC 5 IV over 30 minutes on day 1, and 850 mg metformin hydrochloride PO BID (approximately every 10-12 hours apart) on days 1-21 (QD in course 1). Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive maintenance therapy comprising metformin hydrochloride PO BID on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Arm II (Paclitaxel, Carboplatin, Placebo) n=235 Participants Patients receive 175 mg/m2 paclitaxel IV and carboplatin AUC 5 IV as in Arm I. Patients also receive placebo PO BID (approximately every 10-12 hours apart) on days 1-21 (QD in course 1). Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive maintenance therapy comprising placebo PO BID on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Progression-free Survival (PFS) (Phase II)	9.0 Months Interval 8.4 to 10.5	8.5 Months Interval 8.0 to 10.3

PRIMARY outcome

Timeframe: From date of study entry to time of death or the date of last contact, assessed up to 5 years

Population: All patients.

The observed length of life from randomization into the study to death or the date of last contact. This study was originally designed as a phase II/III study. It passed the phase 2 threshold and started the phase 3; however, a phase 3 interim analysis stopped the trial for futility. Therefore, data available for Phase III may be identical to data reported for Phase II or Phase II/III combined.

Outcome measures

Measure	Arm I (Paclitaxel, Carboplatin, Metformin Hydrochloride) n=234 Participants Patients receive 175 mg/m2 paclitaxel IV over 3 hours on day 1, carboplatin AUC 5 IV over 30 minutes on day 1, and 850 mg metformin hydrochloride PO BID (approximately every 10-12 hours apart) on days 1-21 (QD in course 1). Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive maintenance therapy comprising metformin hydrochloride PO BID on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Arm II (Paclitaxel, Carboplatin, Placebo) n=235 Participants Patients receive 175 mg/m2 paclitaxel IV and carboplatin AUC 5 IV as in Arm I. Patients also receive placebo PO BID (approximately every 10-12 hours apart) on days 1-21 (QD in course 1). Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive maintenance therapy comprising placebo PO BID on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Overall Survival (OS) (Phase II and III)	34.6 Months Interval 28.0 to 50.1	30.4 Months Interval 24.6 to 37.8

SECONDARY outcome

Timeframe: During study treatment, up to 5 years.

Population: Evaluable for response

The proportion of patients who had a response (complete or partial) by RECIST 1.1. Measurable disease is defined by RECIST (version 1.1). Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded). Each lesion must be ≥ 10 mm when measured by CT, MRI or caliper measurement by clinical exam; or ≥ 20 mm when measured by chest x-ray. Lymph nodes must be > 15 mm in short axis when measured by CT or MRI.

Outcome measures

Measure	Arm I (Paclitaxel, Carboplatin, Metformin Hydrochloride) n=164 Participants Patients receive 175 mg/m2 paclitaxel IV over 3 hours on day 1, carboplatin AUC 5 IV over 30 minutes on day 1, and 850 mg metformin hydrochloride PO BID (approximately every 10-12 hours apart) on days 1-21 (QD in course 1). Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive maintenance therapy comprising metformin hydrochloride PO BID on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Arm II (Paclitaxel, Carboplatin, Placebo) n=171 Participants Patients receive 175 mg/m2 paclitaxel IV and carboplatin AUC 5 IV as in Arm I. Patients also receive placebo PO BID (approximately every 10-12 hours apart) on days 1-21 (QD in course 1). Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive maintenance therapy comprising placebo PO BID on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Proportion of Patients Responding to Therapy	61.6 percentage of patients Interval 53.7 to 69.1	60.2 percentage of patients Interval 52.5 to 67.6

SECONDARY outcome

Timeframe: From the date of response to disease progression, death, or date last seen assessed up to 5 years

Population: Patients who responded

Duration of response until disease progression, death, or date last seen among patients who responded.

Outcome measures

Measure	Arm I (Paclitaxel, Carboplatin, Metformin Hydrochloride) n=101 Participants Patients receive 175 mg/m2 paclitaxel IV over 3 hours on day 1, carboplatin AUC 5 IV over 30 minutes on day 1, and 850 mg metformin hydrochloride PO BID (approximately every 10-12 hours apart) on days 1-21 (QD in course 1). Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive maintenance therapy comprising metformin hydrochloride PO BID on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Arm II (Paclitaxel, Carboplatin, Placebo) n=103 Participants Patients receive 175 mg/m2 paclitaxel IV and carboplatin AUC 5 IV as in Arm I. Patients also receive placebo PO BID (approximately every 10-12 hours apart) on days 1-21 (QD in course 1). Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive maintenance therapy comprising placebo PO BID on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Duration of Response by Treatment	8.0 Months Interval 6.3 to 9.4	8.0 Months Interval 6.2 to 10.3

SECONDARY outcome

Timeframe: From date of study entry to time of death or the date of last contact, assessed up to 5 years.

Population: All patients

The observed length of life from randomization into the study to death or the date of last contact. For response, only those patients who had measurable disease were included in an analysis of response. Non-measurable patients are included in the ITT analysis. This study was originally designed as a phase II/III study. It passed the phase 2 threshold and started the phase 3; however, a phase 3 interim analysis stopped the trial for futility. Therefore, data available for Phase III may be identical to data reported for Phase II or Phase II/III combined.

Outcome measures

Measure	Arm I (Paclitaxel, Carboplatin, Metformin Hydrochloride) n=234 Participants Patients receive 175 mg/m2 paclitaxel IV over 3 hours on day 1, carboplatin AUC 5 IV over 30 minutes on day 1, and 850 mg metformin hydrochloride PO BID (approximately every 10-12 hours apart) on days 1-21 (QD in course 1). Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive maintenance therapy comprising metformin hydrochloride PO BID on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Arm II (Paclitaxel, Carboplatin, Placebo) n=235 Participants Patients receive 175 mg/m2 paclitaxel IV and carboplatin AUC 5 IV as in Arm I. Patients also receive placebo PO BID (approximately every 10-12 hours apart) on days 1-21 (QD in course 1). Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive maintenance therapy comprising placebo PO BID on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Overall Survival (OS) (Phase II)	34.6 Months Interval 28.0 to 50.1	30.4 Months Interval 24.6 to 37.8

SECONDARY outcome

Timeframe: From date of study entry to time of progression or death, whichever occurs first, assessed up to 5 years

Population: All patients.

Time until disease progression, death, or date of last contact. For response, only those patients who had measurable disease were included in an analysis of response. Non-measurable patients are included in the ITT analysis. This study was originally designed as a phase II/III study. It passed the phase 2 threshold and started the phase 3; however, a phase 3 interim analysis stopped the trial for futility. Therefore, data available for Phase III may be identical to data reported for Phase II or Phase II/III combined.

Outcome measures

Measure	Arm I (Paclitaxel, Carboplatin, Metformin Hydrochloride) n=234 Participants Patients receive 175 mg/m2 paclitaxel IV over 3 hours on day 1, carboplatin AUC 5 IV over 30 minutes on day 1, and 850 mg metformin hydrochloride PO BID (approximately every 10-12 hours apart) on days 1-21 (QD in course 1). Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive maintenance therapy comprising metformin hydrochloride PO BID on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Arm II (Paclitaxel, Carboplatin, Placebo) n=235 Participants Patients receive 175 mg/m2 paclitaxel IV and carboplatin AUC 5 IV as in Arm I. Patients also receive placebo PO BID (approximately every 10-12 hours apart) on days 1-21 (QD in course 1). Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive maintenance therapy comprising placebo PO BID on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Progression Free Survival (PFS) (Phase III)	9.0 Months Interval 8.4 to 10.5	8.5 Months Interval 8.0 to 10.3

SECONDARY outcome

Timeframe: Up to 5 years

Population: All patients.

Toxicities will be assessed by organ or organ system. For each category of toxicity, each patient will be evaluated by the worst grade experienced during the course of therapy. Data will be summarized by frequency and severity according to the regimen administered. The number of patients with a grade three or greater adverse event will be reported (by system organ class).

Outcome measures

Measure	Arm I (Paclitaxel, Carboplatin, Metformin Hydrochloride) n=234 Participants Patients receive 175 mg/m2 paclitaxel IV over 3 hours on day 1, carboplatin AUC 5 IV over 30 minutes on day 1, and 850 mg metformin hydrochloride PO BID (approximately every 10-12 hours apart) on days 1-21 (QD in course 1). Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive maintenance therapy comprising metformin hydrochloride PO BID on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Arm II (Paclitaxel, Carboplatin, Placebo) n=235 Participants Patients receive 175 mg/m2 paclitaxel IV and carboplatin AUC 5 IV as in Arm I. Patients also receive placebo PO BID (approximately every 10-12 hours apart) on days 1-21 (QD in course 1). Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive maintenance therapy comprising placebo PO BID on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Number of Participants With Grade 3 or Higher Adverse Events as Assessed by Common Terminology Criteria for Adverse Events Version 4 Infections and infestations	14 Participants	10 Participants
Number of Participants With Grade 3 or Higher Adverse Events as Assessed by Common Terminology Criteria for Adverse Events Version 4 Blood and lymphatic system disorders	23 Participants	17 Participants
Number of Participants With Grade 3 or Higher Adverse Events as Assessed by Common Terminology Criteria for Adverse Events Version 4 Cardiac disorders	2 Participants	2 Participants
Number of Participants With Grade 3 or Higher Adverse Events as Assessed by Common Terminology Criteria for Adverse Events Version 4 Ear and labyrinth disorders	1 Participants	0 Participants
Number of Participants With Grade 3 or Higher Adverse Events as Assessed by Common Terminology Criteria for Adverse Events Version 4 Endocrine disorders	0 Participants	0 Participants
Number of Participants With Grade 3 or Higher Adverse Events as Assessed by Common Terminology Criteria for Adverse Events Version 4 Eye disorders	0 Participants	0 Participants
Number of Participants With Grade 3 or Higher Adverse Events as Assessed by Common Terminology Criteria for Adverse Events Version 4 Gastrointestinal disorders	17 Participants	10 Participants
Number of Participants With Grade 3 or Higher Adverse Events as Assessed by Common Terminology Criteria for Adverse Events Version 4 General disorders administration site conditions	5 Participants	6 Participants
Number of Participants With Grade 3 or Higher Adverse Events as Assessed by Common Terminology Criteria for Adverse Events Version 4 Immune system disorders	0 Participants	1 Participants
Number of Participants With Grade 3 or Higher Adverse Events as Assessed by Common Terminology Criteria for Adverse Events Version 4 Injury, poisoning and procedural complications	2 Participants	6 Participants
Number of Participants With Grade 3 or Higher Adverse Events as Assessed by Common Terminology Criteria for Adverse Events Version 4 Investigations	38 Participants	28 Participants
Number of Participants With Grade 3 or Higher Adverse Events as Assessed by Common Terminology Criteria for Adverse Events Version 4 Metabolism and Nutrition Disorders	8 Participants	18 Participants
Number of Participants With Grade 3 or Higher Adverse Events as Assessed by Common Terminology Criteria for Adverse Events Version 4 Musculoskeletal and connective tissue disorders	1 Participants	3 Participants
Number of Participants With Grade 3 or Higher Adverse Events as Assessed by Common Terminology Criteria for Adverse Events Version 4 Neoplasms benign, malignant and unspecified	1 Participants	0 Participants
Number of Participants With Grade 3 or Higher Adverse Events as Assessed by Common Terminology Criteria for Adverse Events Version 4 Nervous system disorders	8 Participants	9 Participants
Number of Participants With Grade 3 or Higher Adverse Events as Assessed by Common Terminology Criteria for Adverse Events Version 4 Psychiatric disorders	0 Participants	2 Participants
Number of Participants With Grade 3 or Higher Adverse Events as Assessed by Common Terminology Criteria for Adverse Events Version 4 Renal and urinary disorders	1 Participants	5 Participants
Number of Participants With Grade 3 or Higher Adverse Events as Assessed by Common Terminology Criteria for Adverse Events Version 4 Reproductive system and breast disorders	1 Participants	0 Participants
Number of Participants With Grade 3 or Higher Adverse Events as Assessed by Common Terminology Criteria for Adverse Events Version 4 Respiratory, thoracic and mediastinal disorders	7 Participants	4 Participants
Number of Participants With Grade 3 or Higher Adverse Events as Assessed by Common Terminology Criteria for Adverse Events Version 4 Skin and subcutaneous tissue disorders	2 Participants	1 Participants
Number of Participants With Grade 3 or Higher Adverse Events as Assessed by Common Terminology Criteria for Adverse Events Version 4 Vascular disorders	10 Participants	18 Participants

SECONDARY outcome

Timeframe: Up to 5 years

Population: All patients

Obesity will be quantitative assessed by body mass index (BMI) and will be assessed for its predictive and prognostic significance. The interaction between BMI and metformin treatment will be examined with an interaction term in a Cox proportional hazards model.

Outcome measures

Measure	Arm I (Paclitaxel, Carboplatin, Metformin Hydrochloride) n=234 Participants Patients receive 175 mg/m2 paclitaxel IV over 3 hours on day 1, carboplatin AUC 5 IV over 30 minutes on day 1, and 850 mg metformin hydrochloride PO BID (approximately every 10-12 hours apart) on days 1-21 (QD in course 1). Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive maintenance therapy comprising metformin hydrochloride PO BID on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Arm II (Paclitaxel, Carboplatin, Placebo) n=235 Participants Patients receive 175 mg/m2 paclitaxel IV and carboplatin AUC 5 IV as in Arm I. Patients also receive placebo PO BID (approximately every 10-12 hours apart) on days 1-21 (QD in course 1). Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive maintenance therapy comprising placebo PO BID on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Level of Obesity	0.4957 proportion of participants obese	0.4979 proportion of participants obese

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 5 years

Hip-to-waist ratio, diabetes status, hemoglobin A1c, fasting insulin glucose levels, and homeostatic model assessment scores will be assessed for their predictive and prognostic significance. Variables will be analyzed as continuous covariates (or as appropriate with transformations such as the logarithm) with Cox models or logistic regression.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 5 years

PIK3CA mutations/amplifications and PIK3R1/PIK3R2 mutations will be examined for prognostic and predictive significance.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 5 years

Expression will be examined by immunohistochemistry with intensity of staining and the percentage of cells staining positive. From these statistics, an H-score will be calculated. Expression will be further dichotomized as high expression and low expression at the median to maximize the power of the study.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 5 years

Levels before and after treatment will be assessed for their predictive and prognostic significance.

Outcome measures

Outcome data not reported

Adverse Events

Arm I (Paclitaxel, Carboplatin, Metformin Hydrochloride)

Serious events: 46 serious events

Other events: 222 other events

Deaths: 95 deaths

Arm II (Paclitaxel, Carboplatin, Placebo)

Serious events: 53 serious events

Other events: 222 other events

Deaths: 95 deaths

Serious adverse events

Measure	Arm I (Paclitaxel, Carboplatin, Metformin Hydrochloride) n=234 participants at risk Patients receive 175 mg/m2 paclitaxel IV over 3 hours on day 1, carboplatin AUC 5 IV over 30 minutes on day 1, and 850 mg metformin hydrochloride PO BID (approximately every 10-12 hours apart) on days 1-21 (QD in course 1). Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive maintenance therapy comprising metformin hydrochloride PO BID on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Arm II (Paclitaxel, Carboplatin, Placebo) n=235 participants at risk Patients receive 175 mg/m2 paclitaxel IV and carboplatin AUC 5 IV as in Arm I. Patients also receive placebo PO BID (approximately every 10-12 hours apart) on days 1-21 (QD in course 1). Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive maintenance therapy comprising placebo PO BID on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Blood and lymphatic system disorders Anemia	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Blood and lymphatic system disorders Febrile Neutropenia	0.85% 2/234 • Patients are followed for the occurrence of adverse events for five years.	1.3% 3/235 • Patients are followed for the occurrence of adverse events for five years.
Cardiac disorders Atrial Fibrillation	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.00% 0/235 • Patients are followed for the occurrence of adverse events for five years.
Cardiac disorders Myocardial Infarction	0.00% 0/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Gastrointestinal disorders Colonic Perforation	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.00% 0/235 • Patients are followed for the occurrence of adverse events for five years.
Gastrointestinal disorders Colitis	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.00% 0/235 • Patients are followed for the occurrence of adverse events for five years.
Gastrointestinal disorders Diarrhea	0.00% 0/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Gastrointestinal disorders Vomiting	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.85% 2/235 • Patients are followed for the occurrence of adverse events for five years.
Gastrointestinal disorders Abdominal Pain	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Gastrointestinal disorders Nausea	0.85% 2/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Gastrointestinal disorders Ascites	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.00% 0/235 • Patients are followed for the occurrence of adverse events for five years.
General disorders Multi-Organ Failure	0.00% 0/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
General disorders Infusion Site Extravasation	0.00% 0/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
General disorders Non-Cardiac Chest Pain	0.00% 0/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
General disorders Fatigue	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.00% 0/235 • Patients are followed for the occurrence of adverse events for five years.
General disorders Fever	0.00% 0/234 • Patients are followed for the occurrence of adverse events for five years.	0.85% 2/235 • Patients are followed for the occurrence of adverse events for five years.
General disorders Infusion Related Reaction	0.85% 2/234 • Patients are followed for the occurrence of adverse events for five years.	0.00% 0/235 • Patients are followed for the occurrence of adverse events for five years.
Immune system disorders Anaphylaxis	0.00% 0/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Immune system disorders Allergic Reaction	0.00% 0/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Infections and infestations Infections And Infestations - Other	0.00% 0/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Infections and infestations Uterine Infection	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.00% 0/235 • Patients are followed for the occurrence of adverse events for five years.
Infections and infestations Soft Tissue Infection	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.00% 0/235 • Patients are followed for the occurrence of adverse events for five years.
Infections and infestations Skin Infection	0.85% 2/234 • Patients are followed for the occurrence of adverse events for five years.	0.00% 0/235 • Patients are followed for the occurrence of adverse events for five years.
Infections and infestations Sepsis	1.3% 3/234 • Patients are followed for the occurrence of adverse events for five years.	2.1% 5/235 • Patients are followed for the occurrence of adverse events for five years.
Infections and infestations Lung Infection	1.7% 4/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Infections and infestations Device Related Infection	0.00% 0/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Infections and infestations Urinary Tract Infection	0.85% 2/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Infections and infestations Catheter Related Infection	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Infections and infestations Bronchial Infection	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.00% 0/235 • Patients are followed for the occurrence of adverse events for five years.
Infections and infestations Biliary Tract Infection	0.00% 0/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Infections and infestations Appendicitis	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.00% 0/235 • Patients are followed for the occurrence of adverse events for five years.
Infections and infestations Abdominal Infection	0.00% 0/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Injury, poisoning and procedural complications Wound Dehiscence	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.00% 0/235 • Patients are followed for the occurrence of adverse events for five years.
Injury, poisoning and procedural complications Hip Fracture	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.00% 0/235 • Patients are followed for the occurrence of adverse events for five years.
Injury, poisoning and procedural complications Fracture	0.00% 0/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Injury, poisoning and procedural complications Fall	0.00% 0/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Investigations Weight Loss	0.85% 2/234 • Patients are followed for the occurrence of adverse events for five years.	0.00% 0/235 • Patients are followed for the occurrence of adverse events for five years.
Investigations Creatinine Increased	0.00% 0/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Investigations Neutrophil Count Decreased	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Investigations Blood Bilirubin Increased	0.00% 0/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Metabolism and nutrition disorders Hyponatremia	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.00% 0/235 • Patients are followed for the occurrence of adverse events for five years.
Metabolism and nutrition disorders Hypokalemia	0.00% 0/234 • Patients are followed for the occurrence of adverse events for five years.	0.85% 2/235 • Patients are followed for the occurrence of adverse events for five years.
Metabolism and nutrition disorders Hypocalcemia	0.00% 0/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Metabolism and nutrition disorders Hypercalcemia	0.00% 0/234 • Patients are followed for the occurrence of adverse events for five years.	0.85% 2/235 • Patients are followed for the occurrence of adverse events for five years.
Metabolism and nutrition disorders Dehydration	0.00% 0/234 • Patients are followed for the occurrence of adverse events for five years.	0.85% 2/235 • Patients are followed for the occurrence of adverse events for five years.
Musculoskeletal and connective tissue disorders Bone Pain	0.00% 0/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Musculoskeletal and connective tissue disorders Back Pain	0.00% 0/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms Benign, Malignant And Unspecified (Incl	0.00% 0/234 • Patients are followed for the occurrence of adverse events for five years.	1.3% 3/235 • Patients are followed for the occurrence of adverse events for five years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Leukemia Secondary To Oncology Chemotherapy	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.00% 0/235 • Patients are followed for the occurrence of adverse events for five years.
Nervous system disorders Stroke	0.00% 0/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Nervous system disorders Peripheral Sensory Neuropathy	0.00% 0/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Nervous system disorders Peripheral Motor Neuropathy	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.00% 0/235 • Patients are followed for the occurrence of adverse events for five years.
Nervous system disorders Neuralgia	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.00% 0/235 • Patients are followed for the occurrence of adverse events for five years.
Nervous system disorders Ischemia Cerebrovascular	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.00% 0/235 • Patients are followed for the occurrence of adverse events for five years.
Nervous system disorders Intracranial Hemorrhage	0.00% 0/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Nervous system disorders Headache	0.00% 0/234 • Patients are followed for the occurrence of adverse events for five years.	0.85% 2/235 • Patients are followed for the occurrence of adverse events for five years.
Nervous system disorders Syncope	1.3% 3/234 • Patients are followed for the occurrence of adverse events for five years.	0.00% 0/235 • Patients are followed for the occurrence of adverse events for five years.
Nervous system disorders Dizziness	0.85% 2/234 • Patients are followed for the occurrence of adverse events for five years.	0.00% 0/235 • Patients are followed for the occurrence of adverse events for five years.
Psychiatric disorders Psychosis	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.00% 0/235 • Patients are followed for the occurrence of adverse events for five years.
Renal and urinary disorders Bladder Perforation	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.00% 0/235 • Patients are followed for the occurrence of adverse events for five years.
Renal and urinary disorders Acute Kidney Injury	0.85% 2/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Respiratory, thoracic and mediastinal disorders Respiratory, Thoracic And Mediastinal Disorders -	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.00% 0/235 • Patients are followed for the occurrence of adverse events for five years.
Respiratory, thoracic and mediastinal disorders Respiratory Failure	0.00% 0/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Respiratory, thoracic and mediastinal disorders Pleural Effusion	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.00% 0/235 • Patients are followed for the occurrence of adverse events for five years.
Respiratory, thoracic and mediastinal disorders Dyspnea	0.00% 0/234 • Patients are followed for the occurrence of adverse events for five years.	1.3% 3/235 • Patients are followed for the occurrence of adverse events for five years.
Respiratory, thoracic and mediastinal disorders Adult Respiratory Distress Syndrome	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.00% 0/235 • Patients are followed for the occurrence of adverse events for five years.
Vascular disorders Thromboembolic Event	1.7% 4/234 • Patients are followed for the occurrence of adverse events for five years.	2.6% 6/235 • Patients are followed for the occurrence of adverse events for five years.
Vascular disorders Hypotension	0.00% 0/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Vascular disorders Hypertension	0.00% 0/234 • Patients are followed for the occurrence of adverse events for five years.	0.85% 2/235 • Patients are followed for the occurrence of adverse events for five years.
Vascular disorders Hematoma	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.00% 0/235 • Patients are followed for the occurrence of adverse events for five years.

Other adverse events

Measure	Arm I (Paclitaxel, Carboplatin, Metformin Hydrochloride) n=234 participants at risk Patients receive 175 mg/m2 paclitaxel IV over 3 hours on day 1, carboplatin AUC 5 IV over 30 minutes on day 1, and 850 mg metformin hydrochloride PO BID (approximately every 10-12 hours apart) on days 1-21 (QD in course 1). Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive maintenance therapy comprising metformin hydrochloride PO BID on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.	Arm II (Paclitaxel, Carboplatin, Placebo) n=235 participants at risk Patients receive 175 mg/m2 paclitaxel IV and carboplatin AUC 5 IV as in Arm I. Patients also receive placebo PO BID (approximately every 10-12 hours apart) on days 1-21 (QD in course 1). Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive maintenance therapy comprising placebo PO BID on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Blood and lymphatic system disorders Thrombotic Thrombocytopenic Purpura	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.00% 0/235 • Patients are followed for the occurrence of adverse events for five years.
Blood and lymphatic system disorders Lymph Node Pain	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Blood and lymphatic system disorders Leukocytosis	0.85% 2/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Blood and lymphatic system disorders Anemia	71.8% 168/234 • Patients are followed for the occurrence of adverse events for five years.	65.5% 154/235 • Patients are followed for the occurrence of adverse events for five years.
Blood and lymphatic system disorders Febrile Neutropenia	3.8% 9/234 • Patients are followed for the occurrence of adverse events for five years.	2.1% 5/235 • Patients are followed for the occurrence of adverse events for five years.
Cardiac disorders Atrial Fibrillation	1.3% 3/234 • Patients are followed for the occurrence of adverse events for five years.	0.85% 2/235 • Patients are followed for the occurrence of adverse events for five years.
Cardiac disorders Ventricular Tachycardia	0.00% 0/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Cardiac disorders Supraventricular Tachycardia	0.00% 0/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Cardiac disorders Palpitations	3.8% 9/234 • Patients are followed for the occurrence of adverse events for five years.	5.5% 13/235 • Patients are followed for the occurrence of adverse events for five years.
Cardiac disorders Myocardial Infarction	0.00% 0/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Cardiac disorders Heart Failure	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.00% 0/235 • Patients are followed for the occurrence of adverse events for five years.
Cardiac disorders Restrictive Cardiomyopathy	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.00% 0/235 • Patients are followed for the occurrence of adverse events for five years.
Cardiac disorders Ventricular Arrhythmia	0.00% 0/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Cardiac disorders Sinus Tachycardia	3.0% 7/234 • Patients are followed for the occurrence of adverse events for five years.	3.0% 7/235 • Patients are followed for the occurrence of adverse events for five years.
Cardiac disorders Chest Pain - Cardiac	1.3% 3/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Ear and labyrinth disorders Middle Ear Inflammation	0.00% 0/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Ear and labyrinth disorders Vertigo	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Ear and labyrinth disorders Tinnitus	3.4% 8/234 • Patients are followed for the occurrence of adverse events for five years.	6.8% 16/235 • Patients are followed for the occurrence of adverse events for five years.
Ear and labyrinth disorders Hearing Impaired	2.1% 5/234 • Patients are followed for the occurrence of adverse events for five years.	2.1% 5/235 • Patients are followed for the occurrence of adverse events for five years.
Ear and labyrinth disorders Vestibular Disorder	0.00% 0/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Ear and labyrinth disorders Ear Pain	1.3% 3/234 • Patients are followed for the occurrence of adverse events for five years.	1.3% 3/235 • Patients are followed for the occurrence of adverse events for five years.
Endocrine disorders Hypothyroidism	0.00% 0/234 • Patients are followed for the occurrence of adverse events for five years.	1.7% 4/235 • Patients are followed for the occurrence of adverse events for five years.
Endocrine disorders Hyperthyroidism	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.00% 0/235 • Patients are followed for the occurrence of adverse events for five years.
Eye disorders Uveitis	0.00% 0/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Eye disorders Watering Eyes	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.85% 2/235 • Patients are followed for the occurrence of adverse events for five years.
Eye disorders Flashing Lights	0.85% 2/234 • Patients are followed for the occurrence of adverse events for five years.	0.00% 0/235 • Patients are followed for the occurrence of adverse events for five years.
Eye disorders Cataract	0.85% 2/234 • Patients are followed for the occurrence of adverse events for five years.	0.85% 2/235 • Patients are followed for the occurrence of adverse events for five years.
Eye disorders Photophobia	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.00% 0/235 • Patients are followed for the occurrence of adverse events for five years.
Eye disorders Conjunctivitis	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.00% 0/235 • Patients are followed for the occurrence of adverse events for five years.
Eye disorders Retinopathy	0.00% 0/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Eye disorders Blurred Vision	9.8% 23/234 • Patients are followed for the occurrence of adverse events for five years.	8.9% 21/235 • Patients are followed for the occurrence of adverse events for five years.
Eye disorders Dry Eye	0.85% 2/234 • Patients are followed for the occurrence of adverse events for five years.	1.3% 3/235 • Patients are followed for the occurrence of adverse events for five years.
Eye disorders Floaters	1.3% 3/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Gastrointestinal disorders Dysphagia	3.4% 8/234 • Patients are followed for the occurrence of adverse events for five years.	2.1% 5/235 • Patients are followed for the occurrence of adverse events for five years.
Gastrointestinal disorders Dyspepsia	7.7% 18/234 • Patients are followed for the occurrence of adverse events for five years.	7.7% 18/235 • Patients are followed for the occurrence of adverse events for five years.
Gastrointestinal disorders Dry Mouth	2.6% 6/234 • Patients are followed for the occurrence of adverse events for five years.	1.7% 4/235 • Patients are followed for the occurrence of adverse events for five years.
Gastrointestinal disorders Colonic Perforation	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.00% 0/235 • Patients are followed for the occurrence of adverse events for five years.
Gastrointestinal disorders Colonic Fistula	0.00% 0/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Gastrointestinal disorders Colitis	0.85% 2/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Gastrointestinal disorders Constipation	42.7% 100/234 • Patients are followed for the occurrence of adverse events for five years.	47.2% 111/235 • Patients are followed for the occurrence of adverse events for five years.
Gastrointestinal disorders Diarrhea	56.8% 133/234 • Patients are followed for the occurrence of adverse events for five years.	33.6% 79/235 • Patients are followed for the occurrence of adverse events for five years.
Gastrointestinal disorders Cheilitis	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Gastrointestinal disorders Vomiting	32.1% 75/234 • Patients are followed for the occurrence of adverse events for five years.	26.4% 62/235 • Patients are followed for the occurrence of adverse events for five years.
Gastrointestinal disorders Bloating	3.8% 9/234 • Patients are followed for the occurrence of adverse events for five years.	4.7% 11/235 • Patients are followed for the occurrence of adverse events for five years.
Gastrointestinal disorders Small Intestinal Perforation	0.00% 0/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Gastrointestinal disorders Stomach Pain	2.1% 5/234 • Patients are followed for the occurrence of adverse events for five years.	0.85% 2/235 • Patients are followed for the occurrence of adverse events for five years.
Gastrointestinal disorders Small Intestinal Obstruction	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.85% 2/235 • Patients are followed for the occurrence of adverse events for five years.
Gastrointestinal disorders Anal Hemorrhage	0.85% 2/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Gastrointestinal disorders Rectal Fistula	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.00% 0/235 • Patients are followed for the occurrence of adverse events for five years.
Gastrointestinal disorders Abdominal Pain	24.4% 57/234 • Patients are followed for the occurrence of adverse events for five years.	24.7% 58/235 • Patients are followed for the occurrence of adverse events for five years.
Gastrointestinal disorders Rectal Hemorrhage	1.7% 4/234 • Patients are followed for the occurrence of adverse events for five years.	2.1% 5/235 • Patients are followed for the occurrence of adverse events for five years.
Gastrointestinal disorders Oral Dysesthesia	0.00% 0/234 • Patients are followed for the occurrence of adverse events for five years.	0.85% 2/235 • Patients are followed for the occurrence of adverse events for five years.
Gastrointestinal disorders Mucositis Oral	9.0% 21/234 • Patients are followed for the occurrence of adverse events for five years.	11.5% 27/235 • Patients are followed for the occurrence of adverse events for five years.
Gastrointestinal disorders Lower Gastrointestinal Hemorrhage	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.00% 0/235 • Patients are followed for the occurrence of adverse events for five years.
Gastrointestinal disorders Ileal Obstruction	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.00% 0/235 • Patients are followed for the occurrence of adverse events for five years.
Gastrointestinal disorders Intra-Abdominal Hemorrhage	0.00% 0/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Gastrointestinal disorders Gastrointestinal Pain	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.00% 0/235 • Patients are followed for the occurrence of adverse events for five years.
Gastrointestinal disorders Oral Pain	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	1.7% 4/235 • Patients are followed for the occurrence of adverse events for five years.
Gastrointestinal disorders Abdominal Distension	2.1% 5/234 • Patients are followed for the occurrence of adverse events for five years.	3.0% 7/235 • Patients are followed for the occurrence of adverse events for five years.
Gastrointestinal disorders Nausea	53.8% 126/234 • Patients are followed for the occurrence of adverse events for five years.	53.2% 125/235 • Patients are followed for the occurrence of adverse events for five years.
Gastrointestinal disorders Gastroesophageal Reflux Disease	6.8% 16/234 • Patients are followed for the occurrence of adverse events for five years.	4.7% 11/235 • Patients are followed for the occurrence of adverse events for five years.
Gastrointestinal disorders Rectal Pain	0.85% 2/234 • Patients are followed for the occurrence of adverse events for five years.	0.00% 0/235 • Patients are followed for the occurrence of adverse events for five years.
Gastrointestinal disorders Esophageal Ulcer	0.00% 0/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Gastrointestinal disorders Fecal Incontinence	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	1.3% 3/235 • Patients are followed for the occurrence of adverse events for five years.
Gastrointestinal disorders Hemorrhoidal Hemorrhage	0.00% 0/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Gastrointestinal disorders Hemorrhoids	3.0% 7/234 • Patients are followed for the occurrence of adverse events for five years.	0.85% 2/235 • Patients are followed for the occurrence of adverse events for five years.
Gastrointestinal disorders Ascites	2.6% 6/234 • Patients are followed for the occurrence of adverse events for five years.	1.7% 4/235 • Patients are followed for the occurrence of adverse events for five years.
Gastrointestinal disorders Toothache	1.3% 3/234 • Patients are followed for the occurrence of adverse events for five years.	1.3% 3/235 • Patients are followed for the occurrence of adverse events for five years.
Gastrointestinal disorders Dental Caries	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.00% 0/235 • Patients are followed for the occurrence of adverse events for five years.
Gastrointestinal disorders Flatulence	2.1% 5/234 • Patients are followed for the occurrence of adverse events for five years.	2.1% 5/235 • Patients are followed for the occurrence of adverse events for five years.
Gastrointestinal disorders Gastritis	0.00% 0/234 • Patients are followed for the occurrence of adverse events for five years.	0.85% 2/235 • Patients are followed for the occurrence of adverse events for five years.
General disorders General Disorders And Administration Site Conditio	0.00% 0/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
General disorders Pain	14.1% 33/234 • Patients are followed for the occurrence of adverse events for five years.	11.5% 27/235 • Patients are followed for the occurrence of adverse events for five years.
General disorders Malaise	1.7% 4/234 • Patients are followed for the occurrence of adverse events for five years.	1.7% 4/235 • Patients are followed for the occurrence of adverse events for five years.
General disorders Localized Edema	1.3% 3/234 • Patients are followed for the occurrence of adverse events for five years.	2.1% 5/235 • Patients are followed for the occurrence of adverse events for five years.
General disorders Injection Site Reaction	0.85% 2/234 • Patients are followed for the occurrence of adverse events for five years.	0.00% 0/235 • Patients are followed for the occurrence of adverse events for five years.
General disorders Infusion Site Extravasation	1.3% 3/234 • Patients are followed for the occurrence of adverse events for five years.	0.85% 2/235 • Patients are followed for the occurrence of adverse events for five years.
General disorders Flu Like Symptoms	3.4% 8/234 • Patients are followed for the occurrence of adverse events for five years.	1.3% 3/235 • Patients are followed for the occurrence of adverse events for five years.
General disorders Edema Trunk	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	1.7% 4/235 • Patients are followed for the occurrence of adverse events for five years.
General disorders Non-Cardiac Chest Pain	3.8% 9/234 • Patients are followed for the occurrence of adverse events for five years.	5.1% 12/235 • Patients are followed for the occurrence of adverse events for five years.
General disorders Edema Limbs	19.2% 45/234 • Patients are followed for the occurrence of adverse events for five years.	15.7% 37/235 • Patients are followed for the occurrence of adverse events for five years.
General disorders Edema Face	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.85% 2/235 • Patients are followed for the occurrence of adverse events for five years.
General disorders Fatigue	74.4% 174/234 • Patients are followed for the occurrence of adverse events for five years.	64.3% 151/235 • Patients are followed for the occurrence of adverse events for five years.
General disorders Fever	6.0% 14/234 • Patients are followed for the occurrence of adverse events for five years.	6.4% 15/235 • Patients are followed for the occurrence of adverse events for five years.
General disorders Gait Disturbance	2.6% 6/234 • Patients are followed for the occurrence of adverse events for five years.	1.3% 3/235 • Patients are followed for the occurrence of adverse events for five years.
General disorders Chills	2.6% 6/234 • Patients are followed for the occurrence of adverse events for five years.	6.0% 14/235 • Patients are followed for the occurrence of adverse events for five years.
General disorders Infusion Related Reaction	7.3% 17/234 • Patients are followed for the occurrence of adverse events for five years.	6.8% 16/235 • Patients are followed for the occurrence of adverse events for five years.
Immune system disorders Anaphylaxis	0.00% 0/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Immune system disorders Allergic Reaction	6.0% 14/234 • Patients are followed for the occurrence of adverse events for five years.	5.1% 12/235 • Patients are followed for the occurrence of adverse events for five years.
Immune system disorders Autoimmune Disorder	0.00% 0/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Infections and infestations Infections And Infestations - Other	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.00% 0/235 • Patients are followed for the occurrence of adverse events for five years.
Infections and infestations Wound Infection	0.85% 2/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Infections and infestations Upper Respiratory Infection	3.8% 9/234 • Patients are followed for the occurrence of adverse events for five years.	3.8% 9/235 • Patients are followed for the occurrence of adverse events for five years.
Infections and infestations Tooth Infection	1.3% 3/234 • Patients are followed for the occurrence of adverse events for five years.	0.85% 2/235 • Patients are followed for the occurrence of adverse events for five years.
Infections and infestations Vulval Infection	0.00% 0/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Infections and infestations Soft Tissue Infection	0.85% 2/234 • Patients are followed for the occurrence of adverse events for five years.	0.00% 0/235 • Patients are followed for the occurrence of adverse events for five years.
Infections and infestations Skin Infection	3.0% 7/234 • Patients are followed for the occurrence of adverse events for five years.	2.1% 5/235 • Patients are followed for the occurrence of adverse events for five years.
Infections and infestations Sinusitis	1.3% 3/234 • Patients are followed for the occurrence of adverse events for five years.	2.1% 5/235 • Patients are followed for the occurrence of adverse events for five years.
Infections and infestations Sepsis	3.0% 7/234 • Patients are followed for the occurrence of adverse events for five years.	2.1% 5/235 • Patients are followed for the occurrence of adverse events for five years.
Infections and infestations Rhinitis Infective	0.00% 0/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Infections and infestations Rash Pustular	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.00% 0/235 • Patients are followed for the occurrence of adverse events for five years.
Infections and infestations Otitis Media	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Infections and infestations Papulopustular Rash	0.85% 2/234 • Patients are followed for the occurrence of adverse events for five years.	0.85% 2/235 • Patients are followed for the occurrence of adverse events for five years.
Infections and infestations Otitis Externa	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.00% 0/235 • Patients are followed for the occurrence of adverse events for five years.
Infections and infestations Nail Infection	0.00% 0/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Infections and infestations Mucosal Infection	0.00% 0/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Infections and infestations Lung Infection	1.3% 3/234 • Patients are followed for the occurrence of adverse events for five years.	1.7% 4/235 • Patients are followed for the occurrence of adverse events for five years.
Infections and infestations Kidney Infection	0.00% 0/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Infections and infestations Eye Infection	0.00% 0/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Infections and infestations Conjunctivitis Infective	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Infections and infestations Vaginal Infection	1.7% 4/234 • Patients are followed for the occurrence of adverse events for five years.	0.85% 2/235 • Patients are followed for the occurrence of adverse events for five years.
Infections and infestations Urinary Tract Infection	12.0% 28/234 • Patients are followed for the occurrence of adverse events for five years.	8.9% 21/235 • Patients are followed for the occurrence of adverse events for five years.
Infections and infestations Catheter Related Infection	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Infections and infestations Bronchial Infection	0.85% 2/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Infections and infestations Enterocolitis Infectious	0.00% 0/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Infections and infestations Biliary Tract Infection	0.00% 0/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Infections and infestations Appendicitis	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.00% 0/235 • Patients are followed for the occurrence of adverse events for five years.
Infections and infestations Abdominal Infection	0.00% 0/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Injury, poisoning and procedural complications Wound Dehiscence	1.7% 4/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Injury, poisoning and procedural complications Vascular Access Complication	0.00% 0/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Injury, poisoning and procedural complications Spinal Fracture	0.00% 0/234 • Patients are followed for the occurrence of adverse events for five years.	0.85% 2/235 • Patients are followed for the occurrence of adverse events for five years.
Injury, poisoning and procedural complications Hip Fracture	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.00% 0/235 • Patients are followed for the occurrence of adverse events for five years.
Injury, poisoning and procedural complications Fracture	1.3% 3/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Injury, poisoning and procedural complications Fall	4.7% 11/234 • Patients are followed for the occurrence of adverse events for five years.	3.0% 7/235 • Patients are followed for the occurrence of adverse events for five years.
Injury, poisoning and procedural complications Wound Complication	0.85% 2/234 • Patients are followed for the occurrence of adverse events for five years.	1.3% 3/235 • Patients are followed for the occurrence of adverse events for five years.
Injury, poisoning and procedural complications Dermatitis Radiation	0.00% 0/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Injury, poisoning and procedural complications Bruising	4.3% 10/234 • Patients are followed for the occurrence of adverse events for five years.	6.8% 16/235 • Patients are followed for the occurrence of adverse events for five years.
Injury, poisoning and procedural complications Ankle Fracture	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.85% 2/235 • Patients are followed for the occurrence of adverse events for five years.
Investigations Weight Loss	11.5% 27/234 • Patients are followed for the occurrence of adverse events for five years.	9.4% 22/235 • Patients are followed for the occurrence of adverse events for five years.
Investigations Weight Gain	1.3% 3/234 • Patients are followed for the occurrence of adverse events for five years.	3.8% 9/235 • Patients are followed for the occurrence of adverse events for five years.
Investigations Platelet Count Decreased	38.5% 90/234 • Patients are followed for the occurrence of adverse events for five years.	36.2% 85/235 • Patients are followed for the occurrence of adverse events for five years.
Investigations Lymphocyte Count Increased	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Investigations Lymphocyte Count Decreased	8.1% 19/234 • Patients are followed for the occurrence of adverse events for five years.	8.1% 19/235 • Patients are followed for the occurrence of adverse events for five years.
Investigations Inr Increased	0.00% 0/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Investigations Hemoglobin Increased	0.00% 0/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Investigations Ggt Increased	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.00% 0/235 • Patients are followed for the occurrence of adverse events for five years.
Investigations Creatinine Increased	10.7% 25/234 • Patients are followed for the occurrence of adverse events for five years.	10.6% 25/235 • Patients are followed for the occurrence of adverse events for five years.
Investigations Cholesterol High	0.85% 2/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Investigations Neutrophil Count Decreased	50.0% 117/234 • Patients are followed for the occurrence of adverse events for five years.	50.6% 119/235 • Patients are followed for the occurrence of adverse events for five years.
Investigations Blood Bilirubin Increased	2.1% 5/234 • Patients are followed for the occurrence of adverse events for five years.	1.7% 4/235 • Patients are followed for the occurrence of adverse events for five years.
Investigations White Blood Cell Decreased	57.3% 134/234 • Patients are followed for the occurrence of adverse events for five years.	56.6% 133/235 • Patients are followed for the occurrence of adverse events for five years.
Investigations Aspartate Aminotransferase Increased	8.1% 19/234 • Patients are followed for the occurrence of adverse events for five years.	10.6% 25/235 • Patients are followed for the occurrence of adverse events for five years.
Investigations Alkaline Phosphatase Increased	11.5% 27/234 • Patients are followed for the occurrence of adverse events for five years.	10.2% 24/235 • Patients are followed for the occurrence of adverse events for five years.
Investigations Alanine Aminotransferase Increased	11.5% 27/234 • Patients are followed for the occurrence of adverse events for five years.	10.2% 24/235 • Patients are followed for the occurrence of adverse events for five years.
Investigations Activated Partial Thromboplastin Time Prolonged	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.00% 0/235 • Patients are followed for the occurrence of adverse events for five years.
Metabolism and nutrition disorders Obesity	0.00% 0/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Metabolism and nutrition disorders Hypophosphatemia	1.3% 3/234 • Patients are followed for the occurrence of adverse events for five years.	2.6% 6/235 • Patients are followed for the occurrence of adverse events for five years.
Metabolism and nutrition disorders Hyponatremia	12.4% 29/234 • Patients are followed for the occurrence of adverse events for five years.	13.6% 32/235 • Patients are followed for the occurrence of adverse events for five years.
Metabolism and nutrition disorders Hypomagnesemia	20.9% 49/234 • Patients are followed for the occurrence of adverse events for five years.	13.6% 32/235 • Patients are followed for the occurrence of adverse events for five years.
Metabolism and nutrition disorders Hypokalemia	14.5% 34/234 • Patients are followed for the occurrence of adverse events for five years.	14.9% 35/235 • Patients are followed for the occurrence of adverse events for five years.
Metabolism and nutrition disorders Hypoglycemia	1.7% 4/234 • Patients are followed for the occurrence of adverse events for five years.	1.7% 4/235 • Patients are followed for the occurrence of adverse events for five years.
Metabolism and nutrition disorders Hypocalcemia	7.3% 17/234 • Patients are followed for the occurrence of adverse events for five years.	6.0% 14/235 • Patients are followed for the occurrence of adverse events for five years.
Metabolism and nutrition disorders Hypoalbuminemia	12.0% 28/234 • Patients are followed for the occurrence of adverse events for five years.	16.6% 39/235 • Patients are followed for the occurrence of adverse events for five years.
Metabolism and nutrition disorders Hyperuricemia	0.00% 0/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Metabolism and nutrition disorders Hypertriglyceridemia	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.00% 0/235 • Patients are followed for the occurrence of adverse events for five years.
Metabolism and nutrition disorders Hypernatremia	3.0% 7/234 • Patients are followed for the occurrence of adverse events for five years.	1.7% 4/235 • Patients are followed for the occurrence of adverse events for five years.
Metabolism and nutrition disorders Hypermagnesemia	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.00% 0/235 • Patients are followed for the occurrence of adverse events for five years.
Metabolism and nutrition disorders Hyperkalemia	0.85% 2/234 • Patients are followed for the occurrence of adverse events for five years.	2.6% 6/235 • Patients are followed for the occurrence of adverse events for five years.
Metabolism and nutrition disorders Hyperglycemia	23.9% 56/234 • Patients are followed for the occurrence of adverse events for five years.	19.6% 46/235 • Patients are followed for the occurrence of adverse events for five years.
Metabolism and nutrition disorders Hypercalcemia	5.1% 12/234 • Patients are followed for the occurrence of adverse events for five years.	6.0% 14/235 • Patients are followed for the occurrence of adverse events for five years.
Metabolism and nutrition disorders Glucose Intolerance	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.85% 2/235 • Patients are followed for the occurrence of adverse events for five years.
Metabolism and nutrition disorders Dehydration	6.0% 14/234 • Patients are followed for the occurrence of adverse events for five years.	7.7% 18/235 • Patients are followed for the occurrence of adverse events for five years.
Metabolism and nutrition disorders Anorexia	30.3% 71/234 • Patients are followed for the occurrence of adverse events for five years.	27.7% 65/235 • Patients are followed for the occurrence of adverse events for five years.
Musculoskeletal and connective tissue disorders Pain In Extremity	15.4% 36/234 • Patients are followed for the occurrence of adverse events for five years.	17.9% 42/235 • Patients are followed for the occurrence of adverse events for five years.
Musculoskeletal and connective tissue disorders Osteoporosis	0.00% 0/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Musculoskeletal and connective tissue disorders Neck Pain	1.7% 4/234 • Patients are followed for the occurrence of adverse events for five years.	1.3% 3/235 • Patients are followed for the occurrence of adverse events for five years.
Musculoskeletal and connective tissue disorders Myalgia	19.2% 45/234 • Patients are followed for the occurrence of adverse events for five years.	20.4% 48/235 • Patients are followed for the occurrence of adverse events for five years.
Musculoskeletal and connective tissue disorders Muscle Weakness Upper Limb	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	1.3% 3/235 • Patients are followed for the occurrence of adverse events for five years.
Musculoskeletal and connective tissue disorders Muscle Weakness Lower Limb	1.7% 4/234 • Patients are followed for the occurrence of adverse events for five years.	3.8% 9/235 • Patients are followed for the occurrence of adverse events for five years.
Musculoskeletal and connective tissue disorders Muscle Weakness Left-Sided	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.00% 0/235 • Patients are followed for the occurrence of adverse events for five years.
Musculoskeletal and connective tissue disorders Joint Range Of Motion Decreased Lumbar Spine	0.00% 0/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Musculoskeletal and connective tissue disorders Joint Range Of Motion Decreased	0.00% 0/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Musculoskeletal and connective tissue disorders Generalized Muscle Weakness	10.3% 24/234 • Patients are followed for the occurrence of adverse events for five years.	10.2% 24/235 • Patients are followed for the occurrence of adverse events for five years.
Musculoskeletal and connective tissue disorders Flank Pain	0.85% 2/234 • Patients are followed for the occurrence of adverse events for five years.	1.3% 3/235 • Patients are followed for the occurrence of adverse events for five years.
Musculoskeletal and connective tissue disorders Chest Wall Pain	0.00% 0/234 • Patients are followed for the occurrence of adverse events for five years.	0.85% 2/235 • Patients are followed for the occurrence of adverse events for five years.
Musculoskeletal and connective tissue disorders Buttock Pain	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	1.3% 3/235 • Patients are followed for the occurrence of adverse events for five years.
Musculoskeletal and connective tissue disorders Bone Pain	10.3% 24/234 • Patients are followed for the occurrence of adverse events for five years.	10.2% 24/235 • Patients are followed for the occurrence of adverse events for five years.
Musculoskeletal and connective tissue disorders Back Pain	12.8% 30/234 • Patients are followed for the occurrence of adverse events for five years.	15.3% 36/235 • Patients are followed for the occurrence of adverse events for five years.
Musculoskeletal and connective tissue disorders Arthritis	1.3% 3/234 • Patients are followed for the occurrence of adverse events for five years.	3.0% 7/235 • Patients are followed for the occurrence of adverse events for five years.
Musculoskeletal and connective tissue disorders Arthralgia	18.4% 43/234 • Patients are followed for the occurrence of adverse events for five years.	23.4% 55/235 • Patients are followed for the occurrence of adverse events for five years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumor Pain	1.3% 3/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Leukemia Secondary To Oncology Chemotherapy	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.00% 0/235 • Patients are followed for the occurrence of adverse events for five years.
Nervous system disorders Tremor	1.7% 4/234 • Patients are followed for the occurrence of adverse events for five years.	0.85% 2/235 • Patients are followed for the occurrence of adverse events for five years.
Nervous system disorders Transient Ischemic Attacks	0.00% 0/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Nervous system disorders Stroke	0.00% 0/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Nervous system disorders Seizure	0.85% 2/234 • Patients are followed for the occurrence of adverse events for five years.	0.00% 0/235 • Patients are followed for the occurrence of adverse events for five years.
Nervous system disorders Presyncope	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	1.3% 3/235 • Patients are followed for the occurrence of adverse events for five years.
Nervous system disorders Peripheral Sensory Neuropathy	62.0% 145/234 • Patients are followed for the occurrence of adverse events for five years.	66.8% 157/235 • Patients are followed for the occurrence of adverse events for five years.
Nervous system disorders Peripheral Motor Neuropathy	6.0% 14/234 • Patients are followed for the occurrence of adverse events for five years.	6.8% 16/235 • Patients are followed for the occurrence of adverse events for five years.
Nervous system disorders Paresthesia	8.5% 20/234 • Patients are followed for the occurrence of adverse events for five years.	3.8% 9/235 • Patients are followed for the occurrence of adverse events for five years.
Nervous system disorders Neuralgia	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Nervous system disorders Memory Impairment	3.8% 9/234 • Patients are followed for the occurrence of adverse events for five years.	4.3% 10/235 • Patients are followed for the occurrence of adverse events for five years.
Nervous system disorders Lethargy	1.3% 3/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Nervous system disorders Ischemia Cerebrovascular	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.00% 0/235 • Patients are followed for the occurrence of adverse events for five years.
Nervous system disorders Movements Involuntary	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Nervous system disorders Intracranial Hemorrhage	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Nervous system disorders Headache	18.8% 44/234 • Patients are followed for the occurrence of adverse events for five years.	14.0% 33/235 • Patients are followed for the occurrence of adverse events for five years.
Nervous system disorders Facial Muscle Weakness	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.00% 0/235 • Patients are followed for the occurrence of adverse events for five years.
Nervous system disorders Encephalopathy	0.00% 0/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Nervous system disorders Dysphasia	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.00% 0/235 • Patients are followed for the occurrence of adverse events for five years.
Nervous system disorders Dysgeusia	11.5% 27/234 • Patients are followed for the occurrence of adverse events for five years.	10.6% 25/235 • Patients are followed for the occurrence of adverse events for five years.
Nervous system disorders Dysesthesia	0.00% 0/234 • Patients are followed for the occurrence of adverse events for five years.	0.85% 2/235 • Patients are followed for the occurrence of adverse events for five years.
Nervous system disorders Dysarthria	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.85% 2/235 • Patients are followed for the occurrence of adverse events for five years.
Nervous system disorders Syncope	2.6% 6/234 • Patients are followed for the occurrence of adverse events for five years.	0.00% 0/235 • Patients are followed for the occurrence of adverse events for five years.
Nervous system disorders Dizziness	14.1% 33/234 • Patients are followed for the occurrence of adverse events for five years.	15.7% 37/235 • Patients are followed for the occurrence of adverse events for five years.
Nervous system disorders Depressed Level Of Consciousness	0.00% 0/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Nervous system disorders Concentration Impairment	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Nervous system disorders Cognitive Disturbance	1.7% 4/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Nervous system disorders Ataxia	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.00% 0/235 • Patients are followed for the occurrence of adverse events for five years.
Nervous system disorders Akathisia	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	1.3% 3/235 • Patients are followed for the occurrence of adverse events for five years.
Psychiatric disorders Psychosis	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.00% 0/235 • Patients are followed for the occurrence of adverse events for five years.
Psychiatric disorders Personality Change	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	1.3% 3/235 • Patients are followed for the occurrence of adverse events for five years.
Psychiatric disorders Restlessness	0.00% 0/234 • Patients are followed for the occurrence of adverse events for five years.	0.85% 2/235 • Patients are followed for the occurrence of adverse events for five years.
Psychiatric disorders Insomnia	15.4% 36/234 • Patients are followed for the occurrence of adverse events for five years.	17.9% 42/235 • Patients are followed for the occurrence of adverse events for five years.
Psychiatric disorders Hallucinations	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Psychiatric disorders Depression	12.8% 30/234 • Patients are followed for the occurrence of adverse events for five years.	12.8% 30/235 • Patients are followed for the occurrence of adverse events for five years.
Psychiatric disorders Delirium	0.00% 0/234 • Patients are followed for the occurrence of adverse events for five years.	0.85% 2/235 • Patients are followed for the occurrence of adverse events for five years.
Psychiatric disorders Confusion	1.3% 3/234 • Patients are followed for the occurrence of adverse events for five years.	3.4% 8/235 • Patients are followed for the occurrence of adverse events for five years.
Psychiatric disorders Anxiety	10.3% 24/234 • Patients are followed for the occurrence of adverse events for five years.	16.2% 38/235 • Patients are followed for the occurrence of adverse events for five years.
Psychiatric disorders Agitation	1.3% 3/234 • Patients are followed for the occurrence of adverse events for five years.	2.6% 6/235 • Patients are followed for the occurrence of adverse events for five years.
Renal and urinary disorders Renal And Urinary Disorders - Other	0.00% 0/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Renal and urinary disorders Urinary Urgency	3.0% 7/234 • Patients are followed for the occurrence of adverse events for five years.	2.1% 5/235 • Patients are followed for the occurrence of adverse events for five years.
Renal and urinary disorders Urinary Tract Obstruction	0.00% 0/234 • Patients are followed for the occurrence of adverse events for five years.	0.85% 2/235 • Patients are followed for the occurrence of adverse events for five years.
Renal and urinary disorders Urinary Retention	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.85% 2/235 • Patients are followed for the occurrence of adverse events for five years.
Renal and urinary disorders Urinary Incontinence	5.1% 12/234 • Patients are followed for the occurrence of adverse events for five years.	8.1% 19/235 • Patients are followed for the occurrence of adverse events for five years.
Renal and urinary disorders Urinary Tract Pain	6.0% 14/234 • Patients are followed for the occurrence of adverse events for five years.	6.4% 15/235 • Patients are followed for the occurrence of adverse events for five years.
Renal and urinary disorders Urinary Frequency	8.1% 19/234 • Patients are followed for the occurrence of adverse events for five years.	6.0% 14/235 • Patients are followed for the occurrence of adverse events for five years.
Renal and urinary disorders Urinary Fistula	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.00% 0/235 • Patients are followed for the occurrence of adverse events for five years.
Renal and urinary disorders Renal Calculi	0.00% 0/234 • Patients are followed for the occurrence of adverse events for five years.	0.85% 2/235 • Patients are followed for the occurrence of adverse events for five years.
Renal and urinary disorders Proteinuria	2.1% 5/234 • Patients are followed for the occurrence of adverse events for five years.	1.3% 3/235 • Patients are followed for the occurrence of adverse events for five years.
Renal and urinary disorders Hematuria	3.0% 7/234 • Patients are followed for the occurrence of adverse events for five years.	6.0% 14/235 • Patients are followed for the occurrence of adverse events for five years.
Renal and urinary disorders Cystitis Noninfective	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.85% 2/235 • Patients are followed for the occurrence of adverse events for five years.
Renal and urinary disorders Chronic Kidney Disease	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.85% 2/235 • Patients are followed for the occurrence of adverse events for five years.
Renal and urinary disorders Bladder Spasm	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Renal and urinary disorders Bladder Perforation	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.00% 0/235 • Patients are followed for the occurrence of adverse events for five years.
Renal and urinary disorders Acute Kidney Injury	0.85% 2/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Reproductive system and breast disorders Vaginal Perforation	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.00% 0/235 • Patients are followed for the occurrence of adverse events for five years.
Reproductive system and breast disorders Vaginal Pain	1.3% 3/234 • Patients are followed for the occurrence of adverse events for five years.	0.85% 2/235 • Patients are followed for the occurrence of adverse events for five years.
Reproductive system and breast disorders Vaginal Hemorrhage	4.7% 11/234 • Patients are followed for the occurrence of adverse events for five years.	8.1% 19/235 • Patients are followed for the occurrence of adverse events for five years.
Reproductive system and breast disorders Vaginal Dryness	1.3% 3/234 • Patients are followed for the occurrence of adverse events for five years.	0.85% 2/235 • Patients are followed for the occurrence of adverse events for five years.
Reproductive system and breast disorders Uterine Hemorrhage	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.00% 0/235 • Patients are followed for the occurrence of adverse events for five years.
Reproductive system and breast disorders Perineal Pain	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.00% 0/235 • Patients are followed for the occurrence of adverse events for five years.
Reproductive system and breast disorders Pelvic Pain	3.4% 8/234 • Patients are followed for the occurrence of adverse events for five years.	5.1% 12/235 • Patients are followed for the occurrence of adverse events for five years.
Reproductive system and breast disorders Menorrhagia	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.00% 0/235 • Patients are followed for the occurrence of adverse events for five years.
Reproductive system and breast disorders Vaginal Discharge	4.7% 11/234 • Patients are followed for the occurrence of adverse events for five years.	4.7% 11/235 • Patients are followed for the occurrence of adverse events for five years.
Reproductive system and breast disorders Vaginal Inflammation	0.85% 2/234 • Patients are followed for the occurrence of adverse events for five years.	0.00% 0/235 • Patients are followed for the occurrence of adverse events for five years.
Reproductive system and breast disorders Breast Pain	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Respiratory, thoracic and mediastinal disorders Voice Alteration	0.85% 2/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Respiratory, thoracic and mediastinal disorders Sore Throat	3.4% 8/234 • Patients are followed for the occurrence of adverse events for five years.	2.6% 6/235 • Patients are followed for the occurrence of adverse events for five years.
Respiratory, thoracic and mediastinal disorders Sneezing	0.00% 0/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Respiratory, thoracic and mediastinal disorders Respiratory Failure	0.00% 0/234 • Patients are followed for the occurrence of adverse events for five years.	0.85% 2/235 • Patients are followed for the occurrence of adverse events for five years.
Respiratory, thoracic and mediastinal disorders Postnasal Drip	1.7% 4/234 • Patients are followed for the occurrence of adverse events for five years.	0.85% 2/235 • Patients are followed for the occurrence of adverse events for five years.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.00% 0/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Respiratory, thoracic and mediastinal disorders Pleural Effusion	0.85% 2/234 • Patients are followed for the occurrence of adverse events for five years.	0.85% 2/235 • Patients are followed for the occurrence of adverse events for five years.
Respiratory, thoracic and mediastinal disorders Nasal Congestion	4.3% 10/234 • Patients are followed for the occurrence of adverse events for five years.	1.7% 4/235 • Patients are followed for the occurrence of adverse events for five years.
Respiratory, thoracic and mediastinal disorders Pleuritic Pain	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.00% 0/235 • Patients are followed for the occurrence of adverse events for five years.
Respiratory, thoracic and mediastinal disorders Productive Cough	2.1% 5/234 • Patients are followed for the occurrence of adverse events for five years.	1.7% 4/235 • Patients are followed for the occurrence of adverse events for five years.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.85% 2/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Respiratory, thoracic and mediastinal disorders Hoarseness	1.3% 3/234 • Patients are followed for the occurrence of adverse events for five years.	0.85% 2/235 • Patients are followed for the occurrence of adverse events for five years.
Respiratory, thoracic and mediastinal disorders Sleep Apnea	0.85% 2/234 • Patients are followed for the occurrence of adverse events for five years.	0.00% 0/235 • Patients are followed for the occurrence of adverse events for five years.
Respiratory, thoracic and mediastinal disorders Hiccups	0.00% 0/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Respiratory, thoracic and mediastinal disorders Epistaxis	2.1% 5/234 • Patients are followed for the occurrence of adverse events for five years.	1.7% 4/235 • Patients are followed for the occurrence of adverse events for five years.
Respiratory, thoracic and mediastinal disorders Dyspnea	26.9% 63/234 • Patients are followed for the occurrence of adverse events for five years.	21.7% 51/235 • Patients are followed for the occurrence of adverse events for five years.
Respiratory, thoracic and mediastinal disorders Cough	11.5% 27/234 • Patients are followed for the occurrence of adverse events for five years.	16.2% 38/235 • Patients are followed for the occurrence of adverse events for five years.
Respiratory, thoracic and mediastinal disorders Wheezing	0.85% 2/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Respiratory, thoracic and mediastinal disorders Atelectasis	0.00% 0/234 • Patients are followed for the occurrence of adverse events for five years.	0.85% 2/235 • Patients are followed for the occurrence of adverse events for five years.
Respiratory, thoracic and mediastinal disorders Allergic Rhinitis	5.1% 12/234 • Patients are followed for the occurrence of adverse events for five years.	2.1% 5/235 • Patients are followed for the occurrence of adverse events for five years.
Skin and subcutaneous tissue disorders Urticaria	0.85% 2/234 • Patients are followed for the occurrence of adverse events for five years.	0.00% 0/235 • Patients are followed for the occurrence of adverse events for five years.
Skin and subcutaneous tissue disorders Skin Ulceration	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Skin and subcutaneous tissue disorders Skin Induration	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.00% 0/235 • Patients are followed for the occurrence of adverse events for five years.
Skin and subcutaneous tissue disorders Skin Hyperpigmentation	1.7% 4/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Skin and subcutaneous tissue disorders Scalp Pain	1.3% 3/234 • Patients are followed for the occurrence of adverse events for five years.	1.7% 4/235 • Patients are followed for the occurrence of adverse events for five years.
Skin and subcutaneous tissue disorders Rash Acneiform	4.7% 11/234 • Patients are followed for the occurrence of adverse events for five years.	7.7% 18/235 • Patients are followed for the occurrence of adverse events for five years.
Skin and subcutaneous tissue disorders Purpura	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Skin and subcutaneous tissue disorders Pruritus	6.8% 16/234 • Patients are followed for the occurrence of adverse events for five years.	4.7% 11/235 • Patients are followed for the occurrence of adverse events for five years.
Skin and subcutaneous tissue disorders Pain Of Skin	0.85% 2/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Skin and subcutaneous tissue disorders Rash Maculo-Papular	11.5% 27/234 • Patients are followed for the occurrence of adverse events for five years.	10.2% 24/235 • Patients are followed for the occurrence of adverse events for five years.
Skin and subcutaneous tissue disorders Nail Ridging	0.00% 0/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Skin and subcutaneous tissue disorders Nail Discoloration	1.3% 3/234 • Patients are followed for the occurrence of adverse events for five years.	1.7% 4/235 • Patients are followed for the occurrence of adverse events for five years.
Skin and subcutaneous tissue disorders Telangiectasia	0.00% 0/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Skin and subcutaneous tissue disorders Hyperhidrosis	1.3% 3/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Skin and subcutaneous tissue disorders Dry Skin	5.1% 12/234 • Patients are followed for the occurrence of adverse events for five years.	4.7% 11/235 • Patients are followed for the occurrence of adverse events for five years.
Skin and subcutaneous tissue disorders Bullous Dermatitis	0.43% 1/234 • Patients are followed for the occurrence of adverse events for five years.	0.00% 0/235 • Patients are followed for the occurrence of adverse events for five years.
Skin and subcutaneous tissue disorders Alopecia	62.4% 146/234 • Patients are followed for the occurrence of adverse events for five years.	55.7% 131/235 • Patients are followed for the occurrence of adverse events for five years.
Vascular disorders Thromboembolic Event	8.5% 20/234 • Patients are followed for the occurrence of adverse events for five years.	11.9% 28/235 • Patients are followed for the occurrence of adverse events for five years.
Vascular disorders Superficial Thrombophlebitis	0.00% 0/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Vascular disorders Phlebitis	1.3% 3/234 • Patients are followed for the occurrence of adverse events for five years.	0.43% 1/235 • Patients are followed for the occurrence of adverse events for five years.
Vascular disorders Lymphedema	1.3% 3/234 • Patients are followed for the occurrence of adverse events for five years.	0.85% 2/235 • Patients are followed for the occurrence of adverse events for five years.
Vascular disorders Hypotension	2.1% 5/234 • Patients are followed for the occurrence of adverse events for five years.	3.4% 8/235 • Patients are followed for the occurrence of adverse events for five years.
Vascular disorders Hypertension	17.1% 40/234 • Patients are followed for the occurrence of adverse events for five years.	20.0% 47/235 • Patients are followed for the occurrence of adverse events for five years.
Vascular disorders Hot Flashes	10.3% 24/234 • Patients are followed for the occurrence of adverse events for five years.	11.9% 28/235 • Patients are followed for the occurrence of adverse events for five years.
Vascular disorders Hematoma	0.85% 2/234 • Patients are followed for the occurrence of adverse events for five years.	0.00% 0/235 • Patients are followed for the occurrence of adverse events for five years.
Vascular disorders Flushing	3.0% 7/234 • Patients are followed for the occurrence of adverse events for five years.	1.3% 3/235 • Patients are followed for the occurrence of adverse events for five years.

Additional Information

Christopher Purdy on behalf of Michael Sill, PhD

NRG Oncology

Phone: (716) 845-1300

Email: purdyc@nrgoncology.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: LTE60