Trial Outcomes & Findings for S0421, Docetaxel and Prednisone With or Without Atrasentan in Treating Patients With Stage IV Prostate Cancer and Bone Metastases That Did Not Respond to Previous Hormone Therapy (NCT NCT00134056)

Last Updated: 2021-10-27

Results Overview

Measured from date of registration to date of death due to any cause. Patient last known to be alive are censored at date of last contact.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1038 participants

Primary outcome timeframe

Up to 7 years after study opens

Results posted on

2021-10-27

Participant Flow

Participant milestones

Participant milestones
Measure	Arm I: Placebo Patients receive docetaxel and prednisone as in arm I. Patients also receive oral placebo once daily on days 1-21. Treatment repeat every 21 days for up to 12 courses. Patients with stable or responding disease after course 12 may register for continued oral placebo treatment for up to 52 weeks. docetaxel: Docetaxel given IV and prednisone given orally prednisone: Docetaxel given IV and prednisone given orally placebo: Given orally	Arm II: Atrasentan Patients receive docetaxel IV over 1 hour on day 1. Patients also receive oral atrasentan and oral prednisone once daily on days 1-21. Treatment repeats every 21 days for up to 12 courses. Patients with stable or responding disease after course 12 may register for continued oral atrasentan treatment for up to 52 weeks. atrasentan hydrochloride: Given orally docetaxel: Docetaxel given IV and prednisone given orally prednisone: Docetaxel given IV and prednisone given orally
Randomization STARTED	518	520
Randomization COMPLETED	496	500
Randomization NOT COMPLETED	22	20
Eligible for Protocol Assigned Treatment STARTED	496	500
Eligible for Protocol Assigned Treatment COMPLETED	169	185
Eligible for Protocol Assigned Treatment NOT COMPLETED	327	315

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm I: Placebo Patients receive docetaxel and prednisone as in arm I. Patients also receive oral placebo once daily on days 1-21. Treatment repeat every 21 days for up to 12 courses. Patients with stable or responding disease after course 12 may register for continued oral placebo treatment for up to 52 weeks. docetaxel: Docetaxel given IV and prednisone given orally prednisone: Docetaxel given IV and prednisone given orally placebo: Given orally	Arm II: Atrasentan Patients receive docetaxel IV over 1 hour on day 1. Patients also receive oral atrasentan and oral prednisone once daily on days 1-21. Treatment repeats every 21 days for up to 12 courses. Patients with stable or responding disease after course 12 may register for continued oral atrasentan treatment for up to 52 weeks. atrasentan hydrochloride: Given orally docetaxel: Docetaxel given IV and prednisone given orally prednisone: Docetaxel given IV and prednisone given orally
Randomization Not eligible for assigned treatment	22	20
Eligible for Protocol Assigned Treatment Lack of Efficacy	171	171
Eligible for Protocol Assigned Treatment Adverse Event	81	67
Eligible for Protocol Assigned Treatment Withdrawal by Subject	20	21
Eligible for Protocol Assigned Treatment Other	55	56

Baseline Characteristics

S0421, Docetaxel and Prednisone With or Without Atrasentan in Treating Patients With Stage IV Prostate Cancer and Bone Metastases That Did Not Respond to Previous Hormone Therapy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm I: Placebo n=496 Participants Patients receive docetaxel and prednisone as in arm I. Patients also receive oral placebo once daily on days 1-21. Treatment repeat every 21 days for up to 12 courses. Patients with stable or responding disease after course 12 may register for continued oral placebo treatment for up to 52 weeks. docetaxel: Docetaxel given IV and prednisone given orally prednisone: Docetaxel given IV and prednisone given orally placebo: Given orally	Arm II: Atrasentan n=498 Participants Patients receive docetaxel IV over 1 hour on day 1. Patients also receive oral atrasentan and oral prednisone once daily on days 1-21. Treatment repeats every 21 days for up to 12 courses. Patients with stable or responding disease after course 12 may register for continued oral atrasentan treatment for up to 52 weeks. atrasentan hydrochloride: Given orally docetaxel: Docetaxel given IV and prednisone given orally prednisone: Docetaxel given IV and prednisone given orally	Total n=994 Participants Total of all reporting groups
Age, Continuous	69 years n=5 Participants	69 years n=7 Participants	69 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	496 Participants n=5 Participants	498 Participants n=7 Participants	994 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	20 Participants n=5 Participants	21 Participants n=7 Participants	41 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	476 Participants n=5 Participants	477 Participants n=7 Participants	953 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized White	403 Participants n=5 Participants	403 Participants n=7 Participants	806 Participants n=5 Participants
Race/Ethnicity, Customized Black	64 Participants n=5 Participants	73 Participants n=7 Participants	137 Participants n=5 Participants
Race/Ethnicity, Customized Asian	12 Participants n=5 Participants	8 Participants n=7 Participants	20 Participants n=5 Participants
Race/Ethnicity, Customized Unknown	14 Participants n=5 Participants	10 Participants n=7 Participants	24 Participants n=5 Participants
Serum PSA	67.7 ug/L n=5 Participants	79.0 ug/L n=7 Participants	72.7 ug/L n=5 Participants
Type of Progression at study entry Measurable or evaluable	394 Participants n=5 Participants	407 Participants n=7 Participants	801 Participants n=5 Participants
Type of Progression at study entry PSA increase only	102 Participants n=5 Participants	91 Participants n=7 Participants	193 Participants n=5 Participants
Bisphosphonate use at study entry	305 Participants n=5 Participants	304 Participants n=7 Participants	609 Participants n=5 Participants
Brief Pain Inventory, worst pain >= 4	213 Participants n=5 Participants	210 Participants n=7 Participants	423 Participants n=5 Participants
Brief Pain Inventory, worst pain <4	283 Participants n=5 Participants	288 Participants n=7 Participants	571 Participants n=5 Participants
Metastases Skeletal only	206 Participants n=5 Participants	203 Participants n=7 Participants	409 Participants n=5 Participants
Metastases Lymph nodes	148 Participants n=5 Participants	149 Participants n=7 Participants	297 Participants n=5 Participants
Metastases Lung, liver or brain	94 Participants n=5 Participants	101 Participants n=7 Participants	195 Participants n=5 Participants
Metastases Extraskeletal	48 Participants n=5 Participants	45 Participants n=7 Participants	93 Participants n=5 Participants
Previous prostatectomy	145 Participants n=5 Participants	168 Participants n=7 Participants	313 Participants n=5 Participants
Performance status 2-3	39 Participants n=5 Participants	36 Participants n=7 Participants	75 Participants n=5 Participants
Performance status 0-1	457 Participants n=5 Participants	462 Participants n=7 Participants	919 Participants n=5 Participants
Gleason score 5-6	49 Participants n=5 Participants	52 Participants n=7 Participants	101 Participants n=5 Participants
Gleason score 7	137 Participants n=5 Participants	141 Participants n=7 Participants	278 Participants n=5 Participants
Gleason score 8-10	272 Participants n=5 Participants	275 Participants n=7 Participants	547 Participants n=5 Participants
Gleason score Missing	38 Participants n=5 Participants	30 Participants n=7 Participants	68 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 7 years after study opens

Measured from date of registration to date of death due to any cause. Patient last known to be alive are censored at date of last contact.

Outcome measures

Outcome measures
Measure	Arm I: Placebo n=496 Participants Patients receive docetaxel and prednisone as in arm I. Patients also receive oral placebo once daily on days 1-21. Treatment repeat every 21 days for up to 12 courses. Patients with stable or responding disease after course 12 may register for continued oral placebo treatment for up to 52 weeks. docetaxel: Docetaxel given IV and prednisone given orally prednisone: Docetaxel given IV and prednisone given orally placebo: Given orally	Arm II: Atrasentan n=498 Participants Patients receive docetaxel IV over 1 hour on day 1. Patients also receive oral atrasentan and oral prednisone once daily on days 1-21. Treatment repeats every 21 days for up to 12 courses. Patients with stable or responding disease after course 12 may register for continued oral atrasentan treatment for up to 52 weeks. atrasentan hydrochloride: Given orally docetaxel: Docetaxel given IV and prednisone given orally prednisone: Docetaxel given IV and prednisone given orally
Compare Survival Between a Control or Standard Therapy Arm of Docetaxel + Placebo + Prednisone With Docetaxel + Atrasentan + Prednisone in Patients With Hormone Refractory Prostate Cancer.	17.6 months Interval 16.4 to 20.1	17.8 months Interval 16.4 to 19.8

PRIMARY outcome

Timeframe: Up to 7 years after study opens

Measured from date of registration to date of first observation of progressive disease, or death due to any cause. Patients without progression are censored at date of last contact. Disease progression is defined by confirmed bone disease progression, soft tissue or pain progression.

Outcome measures

Outcome measures
Measure	Arm I: Placebo n=496 Participants Patients receive docetaxel and prednisone as in arm I. Patients also receive oral placebo once daily on days 1-21. Treatment repeat every 21 days for up to 12 courses. Patients with stable or responding disease after course 12 may register for continued oral placebo treatment for up to 52 weeks. docetaxel: Docetaxel given IV and prednisone given orally prednisone: Docetaxel given IV and prednisone given orally placebo: Given orally	Arm II: Atrasentan n=498 Participants Patients receive docetaxel IV over 1 hour on day 1. Patients also receive oral atrasentan and oral prednisone once daily on days 1-21. Treatment repeats every 21 days for up to 12 courses. Patients with stable or responding disease after course 12 may register for continued oral atrasentan treatment for up to 52 weeks. atrasentan hydrochloride: Given orally docetaxel: Docetaxel given IV and prednisone given orally prednisone: Docetaxel given IV and prednisone given orally
Compare Progression-free Survival Between a Control or Standard Therapy Arm of Docetaxel + Placebo + Prednisone With Docetaxel + Atrasentan + Prednisone in Patients With Hormone Refractory Prostate Cancer.	9.1 months Interval 8.4 to 10.2	9.2 months Interval 8.5 to 9.9

SECONDARY outcome

Timeframe: Up to 52 weeks

Population: Only those patients who progressed on study were included in this analysis. The proportion of patients with pain progression is calculated using number of patients with pain progression as the numerator and the total number of patients who progressed on study as the denominator.

Pain progression is defined as patients reporting an increase of at least two Worst Pain points, maintained for at least two consecutive assessments, increase to Level 3 (strong opioid) on the Pain Medication Log Analgesic Code for patients receiving Level 2 (weak opioid) analgesics at randomization, or an increase to Level 2 or 3 analgesics for patients receiving Level 0 or 1 analgesics at randomization.

Outcome measures

Outcome measures
Measure	Arm I: Placebo n=416 Participants Patients receive docetaxel and prednisone as in arm I. Patients also receive oral placebo once daily on days 1-21. Treatment repeat every 21 days for up to 12 courses. Patients with stable or responding disease after course 12 may register for continued oral placebo treatment for up to 52 weeks. docetaxel: Docetaxel given IV and prednisone given orally prednisone: Docetaxel given IV and prednisone given orally placebo: Given orally	Arm II: Atrasentan n=408 Participants Patients receive docetaxel IV over 1 hour on day 1. Patients also receive oral atrasentan and oral prednisone once daily on days 1-21. Treatment repeats every 21 days for up to 12 courses. Patients with stable or responding disease after course 12 may register for continued oral atrasentan treatment for up to 52 weeks. atrasentan hydrochloride: Given orally docetaxel: Docetaxel given IV and prednisone given orally prednisone: Docetaxel given IV and prednisone given orally
Compare Pain Progression Between the Two Study Arms.	59 Participants	41 Participants

SECONDARY outcome

Timeframe: Assessed every 3 weeks up to 52 weeks

Population: patients with hormone-refractory stage IV prostate cancer and bone metastases treated with docetaxel and prednisone combined with either atrasentan vs placebo

Only adverse events that are possibly, probably or definitely related to study drug are reported.

Outcome measures

Outcome measures
Measure	Arm I: Placebo n=486 Participants Patients receive docetaxel and prednisone as in arm I. Patients also receive oral placebo once daily on days 1-21. Treatment repeat every 21 days for up to 12 courses. Patients with stable or responding disease after course 12 may register for continued oral placebo treatment for up to 52 weeks. docetaxel: Docetaxel given IV and prednisone given orally prednisone: Docetaxel given IV and prednisone given orally placebo: Given orally	Arm II: Atrasentan n=492 Participants Patients receive docetaxel IV over 1 hour on day 1. Patients also receive oral atrasentan and oral prednisone once daily on days 1-21. Treatment repeats every 21 days for up to 12 courses. Patients with stable or responding disease after course 12 may register for continued oral atrasentan treatment for up to 52 weeks. atrasentan hydrochloride: Given orally docetaxel: Docetaxel given IV and prednisone given orally prednisone: Docetaxel given IV and prednisone given orally
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Renal failure	4 Participants	2 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Thrombosis/thrombus/embolism	9 Participants	11 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms ALT, SGPT (serum glutamic pyruvic transaminase)	2 Participants	2 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms AST, SGOT	2 Participants	4 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Adult respiratory distress syndrome (ARDS)	3 Participants	0 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Albumin, serum-low (hypoalbuminemia)	3 Participants	0 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Alkaline phosphatase	4 Participants	6 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Allergic reaction/hypersensitivity	5 Participants	6 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Allergy/Immunology-Other (Specify)	0 Participants	1 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Amylase	0 Participants	1 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Anorexia	5 Participants	5 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Arthritis (non-septic)	1 Participants	0 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Aspiration	0 Participants	1 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Auditory/Ear-Other (Specify)	1 Participants	0 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Bilirubin (hyperbilirubinemia)	0 Participants	1 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Blood/Bone Marrow-Other (Specify)	2 Participants	2 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms CNS cerebrovascular ischemia	0 Participants	1 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms CPK (creatine phosphokinase)	2 Participants	0 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Calcium, serum-low (hypocalcemia)	7 Participants	1 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Cardiac Arrhythmia-Other (Specify)	2 Participants	0 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Cardiac General-Other (Specify)	1 Participants	1 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Cardiac troponin I (cTnI)	2 Participants	1 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Cardiac troponin T (cTnT)	1 Participants	0 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Cardiac-ischemia/infarction	2 Participants	1 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Conduction abnormality NOS	1 Participants	0 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Confusion	1 Participants	0 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Constipation	3 Participants	4 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Cough	1 Participants	2 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Creatinine	4 Participants	1 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Dehydration	9 Participants	8 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Diarrhea	10 Participants	7 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Dizziness	3 Participants	1 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Dry mouth/salivary gland (xerostomia)	1 Participants	0 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Dysphagia (difficulty swallowing)	1 Participants	1 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Dyspnea (shortness of breath)	38 Participants	17 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Edema: head and neck	0 Participants	1 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Edema: limb	16 Participants	2 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Edema: trunk/genital	1 Participants	0 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Erectile dysfunction	2 Participants	0 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Esophagitis	0 Participants	1 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Fatigue (asthenia, lethargy, malaise)	60 Participants	40 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Febrile neutropenia	8 Participants	20 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Fever in absence of neutropenia, ANC lt1.0x10e9/L	1 Participants	2 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Fracture	1 Participants	0 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Glucose, serum-high (hyperglycemia)	20 Participants	24 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Glucose, serum-low (hypoglycemia)	1 Participants	0 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Heartburn/dyspepsia	1 Participants	1 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Hemoglobin	47 Participants	22 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Hemolysis	1 Participants	0 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Hemorrhage, Respiratory tract NOS	0 Participants	1 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Hemorrhage, GI - Rectum	1 Participants	0 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Hemorrhage, GI - Stomach	1 Participants	0 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Hemorrhage, GI - Upper GI NOS	0 Participants	1 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Hemorrhage, GU - Bladder	0 Participants	1 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Hemorrhage/Bleeding-Other (Specify)	2 Participants	1 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Hemorrhoids	0 Participants	2 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Hot flashes/flushes	2 Participants	1 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Hypertension	2 Participants	2 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Hypotension	9 Participants	3 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Hypoxia	10 Participants	3 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms INR (of prothrombin time)	3 Participants	1 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Induration/fibrosis (skin and subcutaneous tissue)	1 Participants	0 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Inf (clin/microbio) w/Gr 3-4 neuts - Bladder	1 Participants	2 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Inf (clin/microbio) w/Gr 3-4 neuts - Blood	2 Participants	0 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Inf (clin/microbio) w/Gr 3-4 neuts - Bronchus	0 Participants	1 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Inf (clin/microbio) w/Gr 3-4 neuts - Esophagus	0 Participants	1 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Inf (clin/microbio) w/Gr 3-4 neuts - Lung	11 Participants	6 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Inf (clin/microbio) w/Gr 3-4 neuts - Nerve-periph	1 Participants	0 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Inf (clin/microbio) w/Gr 3-4 neuts - Skin	1 Participants	2 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Inf (clin/microbio) w/Gr 3-4 neuts - Soft tissue	1 Participants	0 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Inf (clin/microbio) w/Gr 3-4 neuts - UTI	4 Participants	3 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Inf (clin/microbio) w/Gr 3-4 neuts - Upper airway	0 Participants	2 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Inf w/normal ANC or Gr 1-2 neutrophils - Blood	2 Participants	1 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Inf w/normal ANC or Gr 1-2 neutrophils - Bronchus	1 Participants	1 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Inf w/normal ANC or Gr 1-2 neutrophils - Colon	1 Participants	0 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Inf w/normal ANC or Gr 1-2 neutrophils - Lung	1 Participants	5 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Inf w/normal ANC or Gr 1-2 neutrophils - Muscle	1 Participants	0 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Inf w/normal ANC or Gr 1-2 neutrophils - Scrotum	0 Participants	1 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Inf w/normal ANC or Gr 1-2 neutrophils - Sinus	1 Participants	0 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Inf w/normal ANC or Gr 1-2 neutrophils - Skin	1 Participants	2 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Inf w/normal ANC or Gr 1-2 neutrophils - Stomach	1 Participants	0 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Inf w/normal ANC or Gr 1-2 neutrophils - Trachea	1 Participants	0 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Inf w/normal ANC or Gr 1-2 neutrophils - UTI	0 Participants	1 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Inf w/normal ANC or Gr 1-2 neutrophils - Ungual	0 Participants	1 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Inf w/unknown ANC - Middle ear (otitis media)	0 Participants	1 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Inf w/unknown ANC - Upper aerodigestive NOS	0 Participants	1 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Infection with unknown ANC - Blood	0 Participants	1 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Infection with unknown ANC - Lung (pneumonia)	3 Participants	0 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Infection with unknown ANC - Upper airway NOS	0 Participants	1 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Infection with unknown ANC - Urinary tract NOS	1 Participants	1 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Infection-Other (Specify)	4 Participants	3 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Insomnia	1 Participants	1 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Left ventricular diastolic dysfunction	1 Participants	0 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Left ventricular systolic dysfunction	3 Participants	2 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Leukocytes (total WBC)	101 Participants	98 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Lipase	0 Participants	1 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Lymphopenia	30 Participants	32 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Magnesium, serum-high (hypermagnesemia)	1 Participants	0 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Metabolic/Laboratory-Other (Specify)	0 Participants	2 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Mood alteration - agitation	1 Participants	0 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Mood alteration - depression	1 Participants	0 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Mucositis/stomatitis (clinical exam) - Oral cavity	2 Participants	2 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Mucositis/stomatitis (clinical exam) - Pharynx	1 Participants	0 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Mucositis/stomatitis (clinical exam) - Stomach	1 Participants	0 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Mucositis/stomatitis (functional/symp) - Esophagus	0 Participants	1 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Mucositis/stomatitis (functional/symp) - Oral cav	3 Participants	3 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Mucositis/stomatitis (functional/symp) - Pharynx	0 Participants	1 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Mucositis/stomatitis (functional/symp) - Rectum	0 Participants	1 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Muscle weakness, not d/t neuropathy - Extrem-lower	2 Participants	1 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Muscle weakness, not d/t neuropathy - body/general	11 Participants	8 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Myocarditis	1 Participants	0 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Nail changes	0 Participants	1 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Nasal cavity/paranasal sinus reactions	2 Participants	0 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Nausea	11 Participants	5 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Neuropathy: motor	7 Participants	6 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Neuropathy: sensory	10 Participants	11 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Neutrophils/granulocytes (ANC/AGC)	140 Participants	154 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Opportunistic inf associated w/gt=Gr 2 lymphopenia	1 Participants	1 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms PTT (Partial thromboplastin time)	1 Participants	0 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Pain - Abdomen NOS	4 Participants	0 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Pain - Back	1 Participants	2 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Pain - Bone	5 Participants	8 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Pain - Chest wall	0 Participants	1 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Pain - Chest/thorax NOS	1 Participants	0 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Pain - Extremity-limb	1 Participants	1 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Pain - Joint	2 Participants	2 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Pain - Muscle	8 Participants	3 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Pain - Neuralgia/peripheral nerve	1 Participants	1 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Pain - Pelvis	0 Participants	1 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Pain-Other (Specify)	0 Participants	1 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Phosphate, serum-low (hypophosphatemia)	3 Participants	0 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Platelets	7 Participants	4 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Pneumonitis/pulmonary infiltrates	7 Participants	0 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Pneumothorax	1 Participants	0 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Potassium, serum-high (hyperkalemia)	2 Participants	1 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Potassium, serum-low (hypokalemia)	11 Participants	2 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Pulmonary/Upper Respiratory-Other (Specify)	0 Participants	1 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Rash: hand-foot skin reaction	1 Participants	0 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Renal/Genitourinary-Other (Specify)	1 Participants	0 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Right ventricular dysfunction (cor pulmonale)	0 Participants	1 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms SVT and nodal arrhythmia - Atrial fibrillation	3 Participants	2 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms SVT and nodal arrhythmia - Atrial flutter	1 Participants	1 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms SVT and nodal arrhythmia - Sinus tachycardia	0 Participants	1 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Sodium, serum-low (hyponatremia)	8 Participants	3 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Somnolence/depressed level of consciousness	1 Participants	0 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Speech impairment (e.g., dysphasia or aphasia)	0 Participants	1 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Sudden death	2 Participants	0 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Syncope (fainting)	3 Participants	1 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Thrombosis/embolism (vascular access-related)	0 Participants	1 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Vasovagal episode	0 Participants	2 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Vomiting	8 Participants	7 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Watery eye (epiphora, tearing)	0 Participants	1 Participants
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms Weight gain	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Up to 7 years after study opens

PSA Partial Response: Greater than or equal to 50% reduction in baseline PSA. There must be no evidence of soft tissue progression, or confirmed none disease progression, or pain progression.

Outcome measures

Outcome measures
Measure	Arm I: Placebo n=496 Participants Patients receive docetaxel and prednisone as in arm I. Patients also receive oral placebo once daily on days 1-21. Treatment repeat every 21 days for up to 12 courses. Patients with stable or responding disease after course 12 may register for continued oral placebo treatment for up to 52 weeks. docetaxel: Docetaxel given IV and prednisone given orally prednisone: Docetaxel given IV and prednisone given orally placebo: Given orally	Arm II: Atrasentan n=498 Participants Patients receive docetaxel IV over 1 hour on day 1. Patients also receive oral atrasentan and oral prednisone once daily on days 1-21. Treatment repeats every 21 days for up to 12 courses. Patients with stable or responding disease after course 12 may register for continued oral atrasentan treatment for up to 52 weeks. atrasentan hydrochloride: Given orally docetaxel: Docetaxel given IV and prednisone given orally prednisone: Docetaxel given IV and prednisone given orally
Compare Prostate Specific Antigen (PSA) Response Rates Between the Experimental Arm and the Standard Arm.	243 Participants	249 Participants

SECONDARY outcome

Timeframe: Up to 52 weeks

Population: 450 (225 in each arm) of 461 patients with measurable disease at trial enrollment were assessable for response by RECIST.

Complete Response (CR): Complete disappearance of all measurable and non-measurable disease. No new lesions. No disease related symptoms. Normalization of markers and other abnormal lab values. PSA ≤ .2 ng/ml. Partial Response (PR): Applies only to patients with at least one measurable lesion. Greater than or equal to 30% decrease under baseline of the sum of longest diameters of all target measurable lesions. No unequivocal progression of non-measurable disease. No new lesions.

Outcome measures

Outcome measures
Measure	Arm I: Placebo n=225 Participants Patients receive docetaxel and prednisone as in arm I. Patients also receive oral placebo once daily on days 1-21. Treatment repeat every 21 days for up to 12 courses. Patients with stable or responding disease after course 12 may register for continued oral placebo treatment for up to 52 weeks. docetaxel: Docetaxel given IV and prednisone given orally prednisone: Docetaxel given IV and prednisone given orally placebo: Given orally	Arm II: Atrasentan n=225 Participants Patients receive docetaxel IV over 1 hour on day 1. Patients also receive oral atrasentan and oral prednisone once daily on days 1-21. Treatment repeats every 21 days for up to 12 courses. Patients with stable or responding disease after course 12 may register for continued oral atrasentan treatment for up to 52 weeks. atrasentan hydrochloride: Given orally docetaxel: Docetaxel given IV and prednisone given orally prednisone: Docetaxel given IV and prednisone given orally
Compare Objective Responses Between the Two Treatment Groups in Patients With Measurable Disease as Defined by RECIST Criteria. Partial response (confirmed)	31 Participants	32 Participants
Compare Objective Responses Between the Two Treatment Groups in Patients With Measurable Disease as Defined by RECIST Criteria. Complete response	0 Participants	0 Participants
Compare Objective Responses Between the Two Treatment Groups in Patients With Measurable Disease as Defined by RECIST Criteria. No response	194 Participants	193 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: up to 18 months study period

Population: There was a large amount of missing data points due to the difficulty of data collection of pain medication logs in addition to a questionnaire.The study team and site staff were only able to obtain complete data for the patients included in this analysis.

Pain palliation is the proportion of patients showing a two-point reduction in the Worst Pain score (WPS) maintained for two consecutive assessments with no increase in analgesic use. Increase in analgesic use is defined as an increase in Analgesic code Level to 2 (weak opioid) or 3 (strong opioid). Patients will be classified as pain palliated or not palliated. Patients with a WPS of "0" will be defined as "stable" if their WPS remains "0" for Weeks 7 and 10 with no increase in analgesic use, but they will not be categorized as responders. Pain palliation response is measured by BPI short form that has the following: yes/no question about pain today; 4 pain rating questions (worst pain, least pain, average pain, and current pain); pain medications and pain relief; 7 items addressing effect of pain on functioning. For patients who continue to receive treatment beyond 12 treatment cycles, the Worst Pain item is measured by Pain Medication Log and Pain Assessment

Outcome measures

Outcome measures
Measure	Arm I: Placebo n=274 Participants Patients receive docetaxel and prednisone as in arm I. Patients also receive oral placebo once daily on days 1-21. Treatment repeat every 21 days for up to 12 courses. Patients with stable or responding disease after course 12 may register for continued oral placebo treatment for up to 52 weeks. docetaxel: Docetaxel given IV and prednisone given orally prednisone: Docetaxel given IV and prednisone given orally placebo: Given orally	Arm II: Atrasentan n=260 Participants Patients receive docetaxel IV over 1 hour on day 1. Patients also receive oral atrasentan and oral prednisone once daily on days 1-21. Treatment repeats every 21 days for up to 12 courses. Patients with stable or responding disease after course 12 may register for continued oral atrasentan treatment for up to 52 weeks. atrasentan hydrochloride: Given orally docetaxel: Docetaxel given IV and prednisone given orally prednisone: Docetaxel given IV and prednisone given orally
Compare Elements of Quality of Life Between Treatment Arms: Pain Palliation Response, as Measured by the Brief Pain Inventory (BPI)	75 Participants	83 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: up to 18 months study period

Functional status will be measured with the Functional Assessment of Cancer Therapy-Prostate (FACT-P) Trial Outcome Index. The FACT-P also addresses four general domains of QOL (physical, functional, emotional, and social well-being subscales) as well as symptom concerns associated with prostate cancer and its treatment.

Outcome measures

Outcome measures
Measure	Arm I: Placebo n=487 Participants Patients receive docetaxel and prednisone as in arm I. Patients also receive oral placebo once daily on days 1-21. Treatment repeat every 21 days for up to 12 courses. Patients with stable or responding disease after course 12 may register for continued oral placebo treatment for up to 52 weeks. docetaxel: Docetaxel given IV and prednisone given orally prednisone: Docetaxel given IV and prednisone given orally placebo: Given orally	Arm II: Atrasentan n=484 Participants Patients receive docetaxel IV over 1 hour on day 1. Patients also receive oral atrasentan and oral prednisone once daily on days 1-21. Treatment repeats every 21 days for up to 12 courses. Patients with stable or responding disease after course 12 may register for continued oral atrasentan treatment for up to 52 weeks. atrasentan hydrochloride: Given orally docetaxel: Docetaxel given IV and prednisone given orally prednisone: Docetaxel given IV and prednisone given orally
Number of Patients With a Change in Functional Status	118 Participants	139 Participants

Adverse Events

Arm I: Placebo

Serious events: 172 serious events

Other events: 476 other events

Deaths: 0 deaths

Arm II: Atrasentan

Serious events: 153 serious events

Other events: 475 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Dr. David I Quinn

University of Southern California Norris Comprehensive Cancer Center

Phone: 3238653956

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Serious adverse events
Measure	Arm I: Placebo n=486 participants at risk Patients receive docetaxel and prednisone as in arm I. Patients also receive oral placebo once daily on days 1-21. Treatment repeat every 21 days for up to 12 courses. Patients with stable or responding disease after course 12 may register for continued oral placebo treatment for up to 52 weeks.	Arm II: Atrasentan n=492 participants at risk Patients receive docetaxel IV over 1 hour on day 1. Patients also receive oral atrasentan and oral prednisone once daily on days 1-21. Treatment repeats every 21 days for up to 12 courses. Patients with stable or responding disease after course 12 may register for continued oral atrasentan treatment for up to 52 weeks.
Blood and lymphatic system disorders DIC (disseminated intravascular coagulation)	0.21% 1/486 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	0.00% 0/492 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Blood and lymphatic system disorders Febrile neutropenia	1.9% 9/486 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	1.8% 9/492 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Blood and lymphatic system disorders Hemoglobin	2.1% 10/486 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	1.0% 5/492 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Cardiac disorders Cardiac General-Other	0.62% 3/486 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	0.00% 0/492 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Cardiac disorders Cardiac-ischemia/infarction	1.4% 7/486 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	0.41% 2/492 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Cardiac disorders Cardiopulmonary arrest, cause unknown (non-fatal)	0.00% 0/486 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	0.41% 2/492 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Cardiac disorders Left ventricular diastolic dysfunction	0.41% 2/486 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	0.00% 0/492 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Cardiac disorders Left ventricular systolic dysfunction	0.21% 1/486 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	0.41% 2/492 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Cardiac disorders Myocarditis	0.21% 1/486 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	0.00% 0/492 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Cardiac disorders Right ventricular dysfunction (cor pulmonale)	0.00% 0/486 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	0.20% 1/492 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Cardiac disorders SVT and nodal arrhythmia - Atrial fibrillation	1.6% 8/486 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	0.61% 3/492 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Cardiac disorders SVT and nodal arrhythmia - Atrial flutter	0.62% 3/486 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	0.41% 2/492 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Cardiac disorders SVT and nodal arrhythmia - Sinus bradycardia	0.21% 1/486 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	0.00% 0/492 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Cardiac disorders Ventricular arrhythmia - PVCs	0.21% 1/486 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	0.00% 0/492 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Cardiac disorders Ventricular arrhythmia - Ventricular fibrillation	0.00% 0/486 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	0.20% 1/492 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Cardiac disorders Ventricular arrhythmia - Ventricular tachycardia	0.21% 1/486 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	0.00% 0/492 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Ear and labyrinth disorders Otitis, middle ear (non-infectious)	0.21% 1/486 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	0.00% 0/492 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Eye disorders Vision-blurred vision	0.00% 0/486 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	0.20% 1/492 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Gastrointestinal disorders Colitis	0.21% 1/486 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	0.00% 0/492 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Gastrointestinal disorders Constipation	0.21% 1/486 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	0.61% 3/492 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Gastrointestinal disorders Diarrhea	1.2% 6/486 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	0.81% 4/492 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Gastrointestinal disorders Distention/bloating, abdominal	0.21% 1/486 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	0.00% 0/492 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Gastrointestinal disorders Dry mouth/salivary gland (xerostomia)	0.21% 1/486 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	0.00% 0/492 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Gastrointestinal disorders Dysphagia (difficulty swallowing)	0.21% 1/486 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	0.20% 1/492 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Gastrointestinal disorders Esophagitis	0.00% 0/486 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	0.20% 1/492 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Gastrointestinal disorders Gastrointestinal-Other	0.21% 1/486 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	0.00% 0/492 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Gastrointestinal disorders Hemorrhage, GI - Abdomen NOS	0.21% 1/486 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	0.00% 0/492 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Gastrointestinal disorders Hemorrhage, GI - Colon	0.21% 1/486 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	0.20% 1/492 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Gastrointestinal disorders Hemorrhage, GI - Duodenum	0.41% 2/486 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	0.41% 2/492 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Gastrointestinal disorders Hemorrhage, GI - Lower GI NOS	0.00% 0/486 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	0.20% 1/492 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Gastrointestinal disorders Hemorrhage, GI - Rectum	0.62% 3/486 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	0.41% 2/492 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Gastrointestinal disorders Hemorrhage, GI - Stomach	0.21% 1/486 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	0.00% 0/492 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Gastrointestinal disorders Hemorrhage, GI - Upper GI NOS	0.21% 1/486 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	0.61% 3/492 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Gastrointestinal disorders Ileus, GI (functional obstruction of bowel)	0.21% 1/486 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	0.00% 0/492 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Gastrointestinal disorders Mucositis/stomatitis (clinical exam) - Esophagus	0.00% 0/486 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	0.20% 1/492 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Gastrointestinal disorders Mucositis/stomatitis (clinical exam) - Oral cavity	0.41% 2/486 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	0.20% 1/492 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Gastrointestinal disorders Nausea	1.0% 5/486 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	1.2% 6/492 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Gastrointestinal disorders Obstruction, GI - Colon	0.00% 0/486 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	0.20% 1/492 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Gastrointestinal disorders Obstruction, GI - Small bowel NOS	0.21% 1/486 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	0.61% 3/492 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Gastrointestinal disorders Pain - Abdomen NOS	1.4% 7/486 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	1.0% 5/492 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.

Other adverse events
Measure	Arm I: Placebo n=486 participants at risk Patients receive docetaxel and prednisone as in arm I. Patients also receive oral placebo once daily on days 1-21. Treatment repeat every 21 days for up to 12 courses. Patients with stable or responding disease after course 12 may register for continued oral placebo treatment for up to 52 weeks.	Arm II: Atrasentan n=492 participants at risk Patients receive docetaxel IV over 1 hour on day 1. Patients also receive oral atrasentan and oral prednisone once daily on days 1-21. Treatment repeats every 21 days for up to 12 courses. Patients with stable or responding disease after course 12 may register for continued oral atrasentan treatment for up to 52 weeks.
Vascular disorders Hot flashes/flushes	13.4% 65/486 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	14.4% 71/492 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Vascular disorders Hypertension	2.9% 14/486 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	7.1% 35/492 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Blood and lymphatic system disorders Hemoglobin	72.0% 350/486 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	67.3% 331/492 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Eye disorders Vision-blurred vision	5.3% 26/486 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	2.8% 14/492 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Eye disorders Watery eye (epiphora, tearing)	7.6% 37/486 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	8.3% 41/492 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Gastrointestinal disorders Constipation	38.1% 185/486 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	35.8% 176/492 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Gastrointestinal disorders Diarrhea	29.4% 143/486 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	30.3% 149/492 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Gastrointestinal disorders Dry mouth/salivary gland (xerostomia)	6.8% 33/486 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	4.7% 23/492 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Gastrointestinal disorders Heartburn/dyspepsia	7.4% 36/486 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	8.7% 43/492 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Gastrointestinal disorders Mucositis/stomatitis (clinical exam) - Oral cavity	8.0% 39/486 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	5.5% 27/492 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Gastrointestinal disorders Mucositis/stomatitis (functional/symp) - Oral cav	6.2% 30/486 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	9.3% 46/492 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Gastrointestinal disorders Nausea	41.4% 201/486 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	38.2% 188/492 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Gastrointestinal disorders Pain - Abdomen NOS	6.0% 29/486 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	9.3% 46/492 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Gastrointestinal disorders Vomiting	16.0% 78/486 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	12.6% 62/492 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
General disorders Edema: limb	58.4% 284/486 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	36.2% 178/492 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
General disorders Fatigue (asthenia, lethargy, malaise)	73.5% 357/486 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	70.3% 346/492 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
General disorders Fever in absence of neutropenia, ANC lt1.0x10e9/L	8.8% 43/486 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	6.1% 30/492 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
General disorders Pain-Other	6.6% 32/486 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	6.9% 34/492 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Injury, poisoning and procedural complications Bruising (in absence of Gr 3-4 thrombocytopenia)	5.6% 27/486 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	4.3% 21/492 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Investigations ALT, SGPT (serum glutamic pyruvic transaminase)	6.8% 33/486 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	7.3% 36/492 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Investigations AST, SGOT	14.6% 71/486 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	16.3% 80/492 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Investigations Alkaline phosphatase	21.8% 106/486 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	23.0% 113/492 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Investigations Creatinine	16.3% 79/486 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	14.4% 71/492 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Investigations Leukocytes (total WBC)	34.0% 165/486 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	33.5% 165/492 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Investigations Lymphopenia	15.6% 76/486 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	14.6% 72/492 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Investigations Metabolic/Laboratory-Other	4.7% 23/486 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	5.5% 27/492 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Investigations Neutrophils/granulocytes (ANC/AGC)	36.8% 179/486 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	36.6% 180/492 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Investigations Platelets	14.6% 71/486 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	9.6% 47/492 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Investigations Weight gain	10.1% 49/486 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	7.3% 36/492 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Investigations Weight loss	8.0% 39/486 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	7.3% 36/492 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Metabolism and nutrition disorders Albumin, serum-low (hypoalbuminemia)	18.7% 91/486 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	18.3% 90/492 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Metabolism and nutrition disorders Anorexia	23.0% 112/486 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	21.5% 106/492 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Metabolism and nutrition disorders Calcium, serum-low (hypocalcemia)	22.4% 109/486 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	15.2% 75/492 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Metabolism and nutrition disorders Dehydration	5.6% 27/486 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	5.9% 29/492 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Metabolism and nutrition disorders Glucose, serum-high (hyperglycemia)	39.3% 191/486 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	41.1% 202/492 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Metabolism and nutrition disorders Potassium, serum-high (hyperkalemia)	7.4% 36/486 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	6.7% 33/492 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Metabolism and nutrition disorders Potassium, serum-low (hypokalemia)	12.1% 59/486 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	9.6% 47/492 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Metabolism and nutrition disorders Sodium, serum-low (hyponatremia)	15.4% 75/486 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	12.4% 61/492 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Musculoskeletal and connective tissue disorders Muscle weakness, not d/t neuropathy - body/general	8.0% 39/486 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	8.9% 44/492 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.
Musculoskeletal and connective tissue disorders Pain - Back	17.5% 85/486 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.	17.5% 86/492 • Assessed every 3 weeks up to 52 weeks Participants were monitored for toxicity every 3 weeks while on protocol therapy or at more frequent intervals appropriate for that participant, as judged by the treating physician.