Trial Outcomes & Findings for SWOG-9346, Hormone Therapy in Treating Men With Stage IV Prostate Cancer (NCT NCT00002651)

Last Updated: 2017-04-17

Results Overview

Non-inferiority test to determine if intermittent combined androgen deprivation (CAD) overall survival is not substantially worse than continuous CAD overall survival. Specifically, the trial is designed for a one-sided test of the hypothesis that the hazard ratio of intermittent CAD to continuous CAD is 1.2. The assumptions used to compute the trial size are an overall type I error rate of 0.05 and a type II error of 0.10 (power = 0.9).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

3040 participants

Primary outcome timeframe

Up to 15 years

Results posted on

2017-04-17

Participant Flow

Participant milestones

Participant milestones
Measure	Combined Androgen Deprivation (CAD) Patients receive goserelin 3.6 mg subcutaneously once a month and oral bicalutamide 50 mg once daily for 7 months.	Continuous Hormonal Therapy Patients continue to receive goserelin 3.6 mg subcutaneously once a month and oral bicalutamide 50 mg once daily until progression of disease	Intermittent Hormonal Therapy Patients are cycled between observation periods and Combined Androgen Deprivation (CAD) periods based on PSA results. Patients undergo observation in the absence of rising prostate-specific antigen (PSA) or clinical symptoms of progressive disease. Patients with rising PSA or progressive disease begin CAD therapy (goserelin 3.6 mg subcutaneously once a month and oral bicalutamide 50 mg once daily ). Patients whose PSA normalizes after 8 cycles of CAD treatment return to observation. Patients whose PSA does not normalize after 8 cycles of CAD treatment continue CAD therapy until progression (1 cycle of CAD treatment = 7 months with 8 injections. There are 2 injections in the first month on Days 1 and 29).
Induction STARTED	3040	0	0
Induction Eligible	2950	0	0
Induction Eligible and Began Protocol Therapy	2950	0	0
Induction COMPLETED	1697	0	0
Induction NOT COMPLETED	1343	0	0
Consolidation and Randomization STARTED	0	867	882
Consolidation and Randomization Eligible	0	765	770
Consolidation and Randomization Assessable for Toxicity	0	732	702
Consolidation and Randomization COMPLETED	0	29	22
Consolidation and Randomization NOT COMPLETED	0	838	860

Reasons for withdrawal

Reasons for withdrawal
Measure	Combined Androgen Deprivation (CAD) Patients receive goserelin 3.6 mg subcutaneously once a month and oral bicalutamide 50 mg once daily for 7 months.	Continuous Hormonal Therapy Patients continue to receive goserelin 3.6 mg subcutaneously once a month and oral bicalutamide 50 mg once daily until progression of disease	Intermittent Hormonal Therapy Patients are cycled between observation periods and Combined Androgen Deprivation (CAD) periods based on PSA results. Patients undergo observation in the absence of rising prostate-specific antigen (PSA) or clinical symptoms of progressive disease. Patients with rising PSA or progressive disease begin CAD therapy (goserelin 3.6 mg subcutaneously once a month and oral bicalutamide 50 mg once daily ). Patients whose PSA normalizes after 8 cycles of CAD treatment return to observation. Patients whose PSA does not normalize after 8 cycles of CAD treatment continue CAD therapy until progression (1 cycle of CAD treatment = 7 months with 8 injections. There are 2 injections in the first month on Days 1 and 29).
Induction Adverse Event	44	0	0
Induction Refusal unrelated to adverse event	50	0	0
Induction Progression/relapse	274	0	0
Induction Death	62	0	0
Induction Other	823	0	0
Induction not eligible	90	0	0
Consolidation and Randomization Adverse Event	0	36	14
Consolidation and Randomization Refusal unrelated to adverse event	0	53	75
Consolidation and Randomization Progression/relapse	0	295	298
Consolidation and Randomization Death	0	38	48
Consolidation and Randomization Other	0	314	313
Consolidation and Randomization not eligible	0	102	112

Baseline Characteristics

SWOG-9346, Hormone Therapy in Treating Men With Stage IV Prostate Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Continuous Hormonal Therapy n=765 Participants Patients continue to receive goserelin 3.6 mg subcutaneously once a month and oral bicalutamide 50 mg once daily until progression of disease	Intermittent Hormonal Therapy n=770 Participants Patients are cycled between observation periods and Combined Androgen Deprivation (CAD) periods based on PSA results. Patients undergo observation in the absence of rising prostate-specific antigen (PSA) or clinical symptoms of progressive disease. Patients with rising PSA or progressive disease begin CAD therapy (goserelin 3.6 mg subcutaneously once a month and oral bicalutamide 50 mg once daily ). Patients whose PSA normalizes after 8 cycles of CAD treatment return to observation. Patients whose PSA does not normalize after 8 cycles of CAD treatment continue CAD therapy until progression (1 cycle of CAD treatment = 7 months with 8 injections. There are 2 injections in the first month on Days 1 and 29).	Total n=1535 Participants Total of all reporting groups
Age, Continuous	70 years n=5 Participants	70 years n=7 Participants	70 years n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	765 Participants n=5 Participants	770 Participants n=7 Participants	1535 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	17 Participants n=5 Participants	23 Participants n=7 Participants	40 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	571 Participants n=5 Participants	564 Participants n=7 Participants	1135 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	177 Participants n=5 Participants	183 Participants n=7 Participants	360 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	2 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants
Race (NIH/OMB) Asian	5 Participants n=5 Participants	8 Participants n=7 Participants	13 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Black or African American	93 Participants n=5 Participants	94 Participants n=7 Participants	187 Participants n=5 Participants
Race (NIH/OMB) White	507 Participants n=5 Participants	519 Participants n=7 Participants	1026 Participants n=5 Participants
Race (NIH/OMB) More than one race	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	154 Participants n=5 Participants	144 Participants n=7 Participants	298 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 15 years

Outcome measures

Outcome measures
Measure	Consolidation Arm I n=765 Participants Patients continue CAD therapy comprising goserelin subcutaneously once a month and oral bicalutamide once daily. Treatment continues in the absence of disease progression. bicalutamide: Given orally goserelin acetate: Given subcutaneously	Consolidation Arm II n=770 Participants Patients undergo observation in the absence of rising prostate-specific antigen (PSA) or clinical symptoms of progressive disease. Patients with rising PSA or progressive disease begin CAD therapy as in consolidation arm I. Patients whose PSA normalizes after 8 courses return to observation. Patients whose PSA does not normalize after 8 courses continue CAD therapy. bicalutamide: Given orally goserelin acetate: Given subcutaneously clinical observation: Patients undergo observation in the absence of rising prostate-specific antigen (PSA) or clinical symptoms of progressive disease.
Overall Survival	5.8 years Interval 5.3 to 6.4	5.1 years Interval 4.8 to 5.5

PRIMARY outcome

Timeframe: 3 months

Population: Only eligible patients with a usable form set for Physical Functioning portion of the SF-36 both at baseline and 3 months were included in this analysis.

This outcome was scored on a scale of 0 to 100, with higher scores indicating better functioning. Change from Baseline in SF-36 Score at 3 Months

Outcome measures

Outcome measures
Measure	Consolidation Arm I n=469 Participants Patients continue CAD therapy comprising goserelin subcutaneously once a month and oral bicalutamide once daily. Treatment continues in the absence of disease progression. bicalutamide: Given orally goserelin acetate: Given subcutaneously	Consolidation Arm II n=475 Participants Patients undergo observation in the absence of rising prostate-specific antigen (PSA) or clinical symptoms of progressive disease. Patients with rising PSA or progressive disease begin CAD therapy as in consolidation arm I. Patients whose PSA normalizes after 8 courses return to observation. Patients whose PSA does not normalize after 8 courses continue CAD therapy. bicalutamide: Given orally goserelin acetate: Given subcutaneously clinical observation: Patients undergo observation in the absence of rising prostate-specific antigen (PSA) or clinical symptoms of progressive disease.
Physical Functioning as Measured by the SF-36	-1.74 units on a scale Standard Error 0.7366	0.09 units on a scale Standard Error 0.8084

PRIMARY outcome

Timeframe: 3 months

Population: Only eligible patients with a usable form set for SF-36 Mental Health Inventory both at baseline and 3 months were included in this analysis.

This outcome was scored on a scale of 0 to 100, with higher scores indicating better functioning. Change from Baseline in SF-36 Score at 3 Months

Outcome measures

Outcome measures
Measure	Consolidation Arm I n=471 Participants Patients continue CAD therapy comprising goserelin subcutaneously once a month and oral bicalutamide once daily. Treatment continues in the absence of disease progression. bicalutamide: Given orally goserelin acetate: Given subcutaneously	Consolidation Arm II n=479 Participants Patients undergo observation in the absence of rising prostate-specific antigen (PSA) or clinical symptoms of progressive disease. Patients with rising PSA or progressive disease begin CAD therapy as in consolidation arm I. Patients whose PSA normalizes after 8 courses return to observation. Patients whose PSA does not normalize after 8 courses continue CAD therapy. bicalutamide: Given orally goserelin acetate: Given subcutaneously clinical observation: Patients undergo observation in the absence of rising prostate-specific antigen (PSA) or clinical symptoms of progressive disease.
Emotional Functioning as Measured by the SF-36 Mental Health Inventory	-0.95 units on a scale Standard Error 0.6804	1.92 units on a scale Standard Error 0.7241

PRIMARY outcome

Timeframe: 3 months

Population: Only eligible patients with a usable answers regarding erectile dysfunction both at baseline and 3 months were included in this analysis.

This outcome was assessed by having patients report whether they had erectile dysfunction (a score of 1) or no erectile dysfunction (a score of 0). This analysis looks at change from Baseline to 3 Months.

Outcome measures

Outcome measures
Measure	Consolidation Arm I n=450 Participants Patients continue CAD therapy comprising goserelin subcutaneously once a month and oral bicalutamide once daily. Treatment continues in the absence of disease progression. bicalutamide: Given orally goserelin acetate: Given subcutaneously	Consolidation Arm II n=466 Participants Patients undergo observation in the absence of rising prostate-specific antigen (PSA) or clinical symptoms of progressive disease. Patients with rising PSA or progressive disease begin CAD therapy as in consolidation arm I. Patients whose PSA normalizes after 8 courses return to observation. Patients whose PSA does not normalize after 8 courses continue CAD therapy. bicalutamide: Given orally goserelin acetate: Given subcutaneously clinical observation: Patients undergo observation in the absence of rising prostate-specific antigen (PSA) or clinical symptoms of progressive disease.
Erectile Dysfunction	2 percentage of participants	-7 percentage of participants

PRIMARY outcome

Timeframe: 3 months

Population: Only eligible patients with a usable answers regarding libido both at baseline and 3 months were included in this analysis.

This outcome was assessed by having patients report whether their interest in sexual activities was very high, high, or moderate (a score of 1) or low or very low (a score of 0). This outcome measure is reporting a change from baseline in the percentage of participants with High Libido at 3 months. "High Libido" is defined as very high, high or moderate interest in sexual activities.

Outcome measures

Outcome measures
Measure	Consolidation Arm I n=45 Participants Patients continue CAD therapy comprising goserelin subcutaneously once a month and oral bicalutamide once daily. Treatment continues in the absence of disease progression. bicalutamide: Given orally goserelin acetate: Given subcutaneously	Consolidation Arm II n=68 Participants Patients undergo observation in the absence of rising prostate-specific antigen (PSA) or clinical symptoms of progressive disease. Patients with rising PSA or progressive disease begin CAD therapy as in consolidation arm I. Patients whose PSA normalizes after 8 courses return to observation. Patients whose PSA does not normalize after 8 courses continue CAD therapy. bicalutamide: Given orally goserelin acetate: Given subcutaneously clinical observation: Patients undergo observation in the absence of rising prostate-specific antigen (PSA) or clinical symptoms of progressive disease.
High Libido	-2 percentage of participants	16 percentage of participants

PRIMARY outcome

Timeframe: 3 months

Population: Only eligible patients with a usable form set for Vitality both at baseline and 3 months were included in this analysis.

This outcome was scored on a scale of 0 to 100, with higher scores indicating better functioning. This analysis looks at mean change from Baseline score to 3 Months.

Outcome measures

Outcome measures
Measure	Consolidation Arm I n=446 Participants Patients continue CAD therapy comprising goserelin subcutaneously once a month and oral bicalutamide once daily. Treatment continues in the absence of disease progression. bicalutamide: Given orally goserelin acetate: Given subcutaneously	Consolidation Arm II n=465 Participants Patients undergo observation in the absence of rising prostate-specific antigen (PSA) or clinical symptoms of progressive disease. Patients with rising PSA or progressive disease begin CAD therapy as in consolidation arm I. Patients whose PSA normalizes after 8 courses return to observation. Patients whose PSA does not normalize after 8 courses continue CAD therapy. bicalutamide: Given orally goserelin acetate: Given subcutaneously clinical observation: Patients undergo observation in the absence of rising prostate-specific antigen (PSA) or clinical symptoms of progressive disease.
Vitality	-1.42 units on a scale Standard Error 0.7379	-0.11 units on a scale Standard Error 0.8154

OTHER_PRE_SPECIFIED outcome

Timeframe: 15 months

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 15 months

Mean of the change in social functioning from randomization

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 15 months

Mean of the change in role functioning from randomization

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 15 months

Outcome measures

Outcome data not reported

Adverse Events

Continuous Hormonal Therapy

Serious events: 19 serious events

Other events: 665 other events

Deaths: 0 deaths

Intermittent Hormonal Therapy

Serious events: 10 serious events

Other events: 609 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Continuous Hormonal Therapy n=732 participants at risk Patients continue to receive goserelin 3.6 mg subcutaneously once a month and oral bicalutamide 50 mg once daily until progression of disease	Intermittent Hormonal Therapy n=702 participants at risk Patients are cycled between observation periods and Combined Androgen Deprivation (CAD) periods based on PSA results. Patients undergo observation in the absence of rising prostate-specific antigen (PSA) or clinical symptoms of progressive disease. Patients with rising PSA or progressive disease begin CAD therapy (goserelin 3.6 mg subcutaneously once a month and oral bicalutamide 50 mg once daily ). Patients whose PSA normalizes after 8 cycles of CAD treatment return to observation. Patients whose PSA does not normalize after 8 cycles of CAD treatment continue CAD therapy until progression (1 cycle of CAD treatment = 7 months with 8 injections. There are 2 injections in the first month on Days 1 and 29).
Cardiac disorders Cardiac ischemia/infarction	0.82% 6/732 • Up to 10 years after registration to Induction Participants were monitored for toxicity every 3 months while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	0.28% 2/702 • Up to 10 years after registration to Induction Participants were monitored for toxicity every 3 months while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Cardiac disorders Cardiovascular-other	0.27% 2/732 • Up to 10 years after registration to Induction Participants were monitored for toxicity every 3 months while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	0.14% 1/702 • Up to 10 years after registration to Induction Participants were monitored for toxicity every 3 months while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Cardiac disorders LVEF decrease/CHF	0.14% 1/732 • Up to 10 years after registration to Induction Participants were monitored for toxicity every 3 months while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	0.14% 1/702 • Up to 10 years after registration to Induction Participants were monitored for toxicity every 3 months while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
General disorders Flu-like symptoms-other	0.68% 5/732 • Up to 10 years after registration to Induction Participants were monitored for toxicity every 3 months while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	0.43% 3/702 • Up to 10 years after registration to Induction Participants were monitored for toxicity every 3 months while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Second primary	0.14% 1/732 • Up to 10 years after registration to Induction Participants were monitored for toxicity every 3 months while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	0.00% 0/702 • Up to 10 years after registration to Induction Participants were monitored for toxicity every 3 months while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Nervous system disorders Cerebrovascular ischemia	0.14% 1/732 • Up to 10 years after registration to Induction Participants were monitored for toxicity every 3 months while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	0.14% 1/702 • Up to 10 years after registration to Induction Participants were monitored for toxicity every 3 months while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Respiratory, thoracic and mediastinal disorders Lung-other	0.00% 0/732 • Up to 10 years after registration to Induction Participants were monitored for toxicity every 3 months while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	0.28% 2/702 • Up to 10 years after registration to Induction Participants were monitored for toxicity every 3 months while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Respiratory, thoracic and mediastinal disorders Pleural effusions	0.14% 1/732 • Up to 10 years after registration to Induction Participants were monitored for toxicity every 3 months while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	0.00% 0/702 • Up to 10 years after registration to Induction Participants were monitored for toxicity every 3 months while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Vascular disorders Hemorrhage-other	0.14% 1/732 • Up to 10 years after registration to Induction Participants were monitored for toxicity every 3 months while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	0.00% 0/702 • Up to 10 years after registration to Induction Participants were monitored for toxicity every 3 months while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Vascular disorders Thrombosis/embolism	0.14% 1/732 • Up to 10 years after registration to Induction Participants were monitored for toxicity every 3 months while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	0.00% 0/702 • Up to 10 years after registration to Induction Participants were monitored for toxicity every 3 months while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.

Other adverse events

Additional Information

Study Statistician

SWOG Statistical Center

Phone: 206-667-4623

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Continuous Hormonal Therapy n=732 participants at risk Patients continue to receive goserelin 3.6 mg subcutaneously once a month and oral bicalutamide 50 mg once daily until progression of disease	Intermittent Hormonal Therapy n=702 participants at risk Patients are cycled between observation periods and Combined Androgen Deprivation (CAD) periods based on PSA results. Patients undergo observation in the absence of rising prostate-specific antigen (PSA) or clinical symptoms of progressive disease. Patients with rising PSA or progressive disease begin CAD therapy (goserelin 3.6 mg subcutaneously once a month and oral bicalutamide 50 mg once daily ). Patients whose PSA normalizes after 8 cycles of CAD treatment return to observation. Patients whose PSA does not normalize after 8 cycles of CAD treatment continue CAD therapy until progression (1 cycle of CAD treatment = 7 months with 8 injections. There are 2 injections in the first month on Days 1 and 29).
Blood and lymphatic system disorders Anemia	11.7% 86/732 • Up to 10 years after registration to Induction Participants were monitored for toxicity every 3 months while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	12.1% 85/702 • Up to 10 years after registration to Induction Participants were monitored for toxicity every 3 months while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Gastrointestinal disorders Constipation/bowel obstruction	11.1% 81/732 • Up to 10 years after registration to Induction Participants were monitored for toxicity every 3 months while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	7.8% 55/702 • Up to 10 years after registration to Induction Participants were monitored for toxicity every 3 months while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Gastrointestinal disorders Diarrhea without colostomy	12.7% 93/732 • Up to 10 years after registration to Induction Participants were monitored for toxicity every 3 months while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	11.3% 79/702 • Up to 10 years after registration to Induction Participants were monitored for toxicity every 3 months while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Gastrointestinal disorders Nausea	7.4% 54/732 • Up to 10 years after registration to Induction Participants were monitored for toxicity every 3 months while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	5.4% 38/702 • Up to 10 years after registration to Induction Participants were monitored for toxicity every 3 months while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
General disorders Fatigue/malaise/lethargy	52.0% 381/732 • Up to 10 years after registration to Induction Participants were monitored for toxicity every 3 months while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	51.9% 364/702 • Up to 10 years after registration to Induction Participants were monitored for toxicity every 3 months while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
General disorders Pain-other	19.1% 140/732 • Up to 10 years after registration to Induction Participants were monitored for toxicity every 3 months while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	18.7% 131/702 • Up to 10 years after registration to Induction Participants were monitored for toxicity every 3 months while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Investigations Alkaline phosphatase increase	7.9% 58/732 • Up to 10 years after registration to Induction Participants were monitored for toxicity every 3 months while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	13.5% 95/702 • Up to 10 years after registration to Induction Participants were monitored for toxicity every 3 months while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Investigations Creatinine increase	14.6% 107/732 • Up to 10 years after registration to Induction Participants were monitored for toxicity every 3 months while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	12.4% 87/702 • Up to 10 years after registration to Induction Participants were monitored for toxicity every 3 months while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Investigations SGOT (AST) increase	6.7% 49/732 • Up to 10 years after registration to Induction Participants were monitored for toxicity every 3 months while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	10.0% 70/702 • Up to 10 years after registration to Induction Participants were monitored for toxicity every 3 months while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Investigations Weight gain	8.2% 60/732 • Up to 10 years after registration to Induction Participants were monitored for toxicity every 3 months while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	4.7% 33/702 • Up to 10 years after registration to Induction Participants were monitored for toxicity every 3 months while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Metabolism and nutrition disorders Hyperglycemia	11.6% 85/732 • Up to 10 years after registration to Induction Participants were monitored for toxicity every 3 months while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	13.0% 91/702 • Up to 10 years after registration to Induction Participants were monitored for toxicity every 3 months while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Musculoskeletal and connective tissue disorders Arthralgia	12.6% 92/732 • Up to 10 years after registration to Induction Participants were monitored for toxicity every 3 months while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	9.0% 63/702 • Up to 10 years after registration to Induction Participants were monitored for toxicity every 3 months while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Musculoskeletal and connective tissue disorders Bone pain	32.7% 239/732 • Up to 10 years after registration to Induction Participants were monitored for toxicity every 3 months while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	38.7% 272/702 • Up to 10 years after registration to Induction Participants were monitored for toxicity every 3 months while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Musculoskeletal and connective tissue disorders Myalgia	6.0% 44/732 • Up to 10 years after registration to Induction Participants were monitored for toxicity every 3 months while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	6.0% 42/702 • Up to 10 years after registration to Induction Participants were monitored for toxicity every 3 months while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Nervous system disorders Dizziness/light headedness	6.0% 44/732 • Up to 10 years after registration to Induction Participants were monitored for toxicity every 3 months while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	5.4% 38/702 • Up to 10 years after registration to Induction Participants were monitored for toxicity every 3 months while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Nervous system disorders Sensory neuropathy	15.2% 111/732 • Up to 10 years after registration to Induction Participants were monitored for toxicity every 3 months while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	13.5% 95/702 • Up to 10 years after registration to Induction Participants were monitored for toxicity every 3 months while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Nervous system disorders Weakness (motor neuropathy)	10.2% 75/732 • Up to 10 years after registration to Induction Participants were monitored for toxicity every 3 months while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	8.7% 61/702 • Up to 10 years after registration to Induction Participants were monitored for toxicity every 3 months while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Psychiatric disorders Anxiety/agitation	5.6% 41/732 • Up to 10 years after registration to Induction Participants were monitored for toxicity every 3 months while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	5.8% 41/702 • Up to 10 years after registration to Induction Participants were monitored for toxicity every 3 months while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Psychiatric disorders Depression	14.6% 107/732 • Up to 10 years after registration to Induction Participants were monitored for toxicity every 3 months while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	13.7% 96/702 • Up to 10 years after registration to Induction Participants were monitored for toxicity every 3 months while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Psychiatric disorders Insomnia	19.3% 141/732 • Up to 10 years after registration to Induction Participants were monitored for toxicity every 3 months while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	17.5% 123/702 • Up to 10 years after registration to Induction Participants were monitored for toxicity every 3 months while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Psychiatric disorders Libido loss	35.8% 262/732 • Up to 10 years after registration to Induction Participants were monitored for toxicity every 3 months while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	32.2% 226/702 • Up to 10 years after registration to Induction Participants were monitored for toxicity every 3 months while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Renal and urinary disorders Urinary frequency/urgency	19.3% 141/732 • Up to 10 years after registration to Induction Participants were monitored for toxicity every 3 months while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	20.9% 147/702 • Up to 10 years after registration to Induction Participants were monitored for toxicity every 3 months while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Reproductive system and breast disorders Erectile impotence	41.5% 304/732 • Up to 10 years after registration to Induction Participants were monitored for toxicity every 3 months while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	36.5% 256/702 • Up to 10 years after registration to Induction Participants were monitored for toxicity every 3 months while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Reproductive system and breast disorders Gynecomastia	24.7% 181/732 • Up to 10 years after registration to Induction Participants were monitored for toxicity every 3 months while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	22.5% 158/702 • Up to 10 years after registration to Induction Participants were monitored for toxicity every 3 months while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Respiratory, thoracic and mediastinal disorders Cough	7.1% 52/732 • Up to 10 years after registration to Induction Participants were monitored for toxicity every 3 months while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	6.1% 43/702 • Up to 10 years after registration to Induction Participants were monitored for toxicity every 3 months while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Respiratory, thoracic and mediastinal disorders Dyspnea	14.9% 109/732 • Up to 10 years after registration to Induction Participants were monitored for toxicity every 3 months while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	16.5% 116/702 • Up to 10 years after registration to Induction Participants were monitored for toxicity every 3 months while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Skin and subcutaneous tissue disorders Rash/desquamation	11.1% 81/732 • Up to 10 years after registration to Induction Participants were monitored for toxicity every 3 months while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	9.3% 65/702 • Up to 10 years after registration to Induction Participants were monitored for toxicity every 3 months while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Skin and subcutaneous tissue disorders Sweating	33.5% 245/732 • Up to 10 years after registration to Induction Participants were monitored for toxicity every 3 months while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	25.1% 176/702 • Up to 10 years after registration to Induction Participants were monitored for toxicity every 3 months while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Vascular disorders Hot flashes	69.8% 511/732 • Up to 10 years after registration to Induction Participants were monitored for toxicity every 3 months while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	62.7% 440/702 • Up to 10 years after registration to Induction Participants were monitored for toxicity every 3 months while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Vascular disorders Hypertension	5.1% 37/732 • Up to 10 years after registration to Induction Participants were monitored for toxicity every 3 months while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	5.1% 36/702 • Up to 10 years after registration to Induction Participants were monitored for toxicity every 3 months while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.