Trial Outcomes & Findings for Chemotherapy With or Without Strontium-89 in Treating Patients With Prostate Cancer (NCT NCT00024167)

Last Updated: 2016-03-22

Results Overview

Overall survival (OS) was computed using the number of months from the date of randomization to the date of death. Participants still alive were censored at the last follow-up date. Kaplan-Meier methodology was used to evaluate OS.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

265 participants

Primary outcome timeframe

Followed every 4 weeks from randomization until death, up to 7 years.

Results posted on

2016-03-22

Participant Flow

Recruitment Period: April 16, 2002 to October 20, 2010 from various hospitals and institutions representing the Community Clinical Oncology Program (CCOP).

Of the 265 participants enrolled - 127 were randomized to either the Sr-89 treatment arm or the no Sr-89 treatment arm and the rest (138 participants) did not qualify for randomization. Of the 138 participants, 5 did not receive any treatment and the rest received only induction treatment. Study was closed prematurely due to issues with accrual.

Participant milestones

Participant milestones
Measure	Induction Treatment + Strontium-89 Induction treatment option 1: Weeks 1,3,5: Doxorubicin 20 mg/m\^2 IV, day 1 and Ketoconazole 400 mg oral 3 x daily, days 1 through 7. Weeks 2,4,6: Vinblastine 4 mg/m\^2 IVPB, day 1 and Estramustine 140 mg oral 3 x daily, days 1 through 7. Weeks 7,8: No treatment. Hydrocortisone 10 mg oral 2 x daily will be administered throughout treatment or Induction treatment option 2: Prednisone 5 mg oral 2 x daily, weeks 1-14 and Docetaxel 75 mg/m\^2 IVPB over 1 hour, every 3 weeks. Dexamethasone 4 mg is given orally at 12 and 1 hours before and 12 hours after docetaxel. Randomization: Doxorubicin IV over 24 hours once weekly for 6 weeks + Strontium-89 IV once at beginning of chemotherapy.	Induction Treatment + No Strontium-89 Induction treatment option 1: Weeks 1,3,5: Doxorubicin 20 mg/m\^2 IV, day 1 and Ketoconazole 400 mg oral 3 x daily, days 1 through 7. Weeks 2,4,6: Vinblastine 4 mg/m\^2 IVPB, day 1 and Estramustine 140 mg oral 3 x daily, days 1 through 7. Weeks 7,8: No treatment. Hydrocortisone 10 mg oral 2 x daily will be administered throughout treatment or Induction treatment option 2: Prednisone 5 mg oral 2 x daily, weeks 1-14 and Docetaxel 75 mg/m\^2 IVPB over 1 hour, every 3 weeks. Dexamethasone 4 mg is given orally at 12 and 1 hours before and 12 hours after docetaxel. Randomization: Doxorubicin 20mg/m\^2 IV over 24 hours once weekly for 6 weeks.
Overall Study STARTED	65	62
Overall Study Induction Treatment Option 1 Completed	22	21
Overall Study Induction Treatment Option 2 Completed	43	41
Overall Study COMPLETED	12	15
Overall Study NOT COMPLETED	53	47

Reasons for withdrawal

Reasons for withdrawal
Measure	Induction Treatment + Strontium-89 Induction treatment option 1: Weeks 1,3,5: Doxorubicin 20 mg/m\^2 IV, day 1 and Ketoconazole 400 mg oral 3 x daily, days 1 through 7. Weeks 2,4,6: Vinblastine 4 mg/m\^2 IVPB, day 1 and Estramustine 140 mg oral 3 x daily, days 1 through 7. Weeks 7,8: No treatment. Hydrocortisone 10 mg oral 2 x daily will be administered throughout treatment or Induction treatment option 2: Prednisone 5 mg oral 2 x daily, weeks 1-14 and Docetaxel 75 mg/m\^2 IVPB over 1 hour, every 3 weeks. Dexamethasone 4 mg is given orally at 12 and 1 hours before and 12 hours after docetaxel. Randomization: Doxorubicin IV over 24 hours once weekly for 6 weeks + Strontium-89 IV once at beginning of chemotherapy.	Induction Treatment + No Strontium-89 Induction treatment option 1: Weeks 1,3,5: Doxorubicin 20 mg/m\^2 IV, day 1 and Ketoconazole 400 mg oral 3 x daily, days 1 through 7. Weeks 2,4,6: Vinblastine 4 mg/m\^2 IVPB, day 1 and Estramustine 140 mg oral 3 x daily, days 1 through 7. Weeks 7,8: No treatment. Hydrocortisone 10 mg oral 2 x daily will be administered throughout treatment or Induction treatment option 2: Prednisone 5 mg oral 2 x daily, weeks 1-14 and Docetaxel 75 mg/m\^2 IVPB over 1 hour, every 3 weeks. Dexamethasone 4 mg is given orally at 12 and 1 hours before and 12 hours after docetaxel. Randomization: Doxorubicin 20mg/m\^2 IV over 24 hours once weekly for 6 weeks.
Overall Study Death	53	47

Baseline Characteristics

Chemotherapy With or Without Strontium-89 in Treating Patients With Prostate Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Induction Treatment n=133 Participants Induction treatment option 1: Weeks 1,3,5: Doxorubicin 20 mg/m\^2 IV, day 1 and Ketoconazole 400 mg oral 3 x daily, days 1 through 7. Weeks 2,4,6: Vinblastine 4 mg/m\^2 IVPB, day 1 and Estramustine 140 mg oral 3 x daily, days 1 through 7. Weeks 7,8: No treatment. Hydrocortisone 10 mg oral 2 x daily will be administered throughout treatment or Induction treatment option 2: Prednisone 5 mg oral 2 x daily, weeks 1-14 and Docetaxel 75 mg/m\^2 IVPB over 1 hour, every 3 weeks. Dexamethasone 4 mg is given orally at 12 and 1 hours before and 12 hours after docetaxel.	Induction Treatment + Strontium-89 n=65 Participants Induction treatment option 1: Weeks 1,3,5: Doxorubicin 20 mg/m\^2 IV, day 1 and Ketoconazole 400 mg oral 3 x daily, days 1 through 7. Weeks 2,4,6: Vinblastine 4 mg/m\^2 IVPB, day 1 and Estramustine 140 mg oral 3 x daily, days 1 through 7. Weeks 7,8: No treatment. Hydrocortisone 10 mg oral 2 x daily will be administered throughout treatment or Induction treatment option 2: Prednisone 5 mg oral 2 x daily, weeks 1-14 and Docetaxel 75 mg/m\^2 IVPB over 1 hour, every 3 weeks. Dexamethasone 4 mg is given orally at 12 and 1 hours before and 12 hours after docetaxel. Randomization: Doxorubicin IV over 24 hours once weekly for 6 weeks + Strontium-89 IV once at beginning of chemotherapy.	Induction Treatment + No Strontium-89 n=62 Participants Induction treatment option 1: Weeks 1,3,5: Doxorubicin 20 mg/m\^2 IV, day 1 and Ketoconazole 400 mg oral 3 x daily, days 1 through 7. Weeks 2,4,6: Vinblastine 4 mg/m\^2 IVPB, day 1 and Estramustine 140 mg oral 3 x daily, days 1 through 7. Weeks 7,8: No treatment. Hydrocortisone 10 mg oral 2 x daily will be administered throughout treatment or Induction treatment option 2: Prednisone 5 mg oral 2 x daily, weeks 1-14 and Docetaxel 75 mg/m\^2 IVPB over 1 hour, every 3 weeks. Dexamethasone 4 mg is given orally at 12 and 1 hours before and 12 hours after docetaxel. Randomization: Doxorubicin 20mg/m\^2 IV over 24 hours once weekly for 6 weeks.	Total n=260 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants	1 Participants n=483 Participants
Age, Categorical Between 18 and 65 years	53 Participants n=93 Participants	22 Participants n=4 Participants	23 Participants n=27 Participants	98 Participants n=483 Participants
Age, Categorical >=65 years	80 Participants n=93 Participants	43 Participants n=4 Participants	38 Participants n=27 Participants	161 Participants n=483 Participants
Age, Continuous	67 years n=93 Participants	68 years n=4 Participants	67 years n=27 Participants	67 years n=483 Participants
Sex: Female, Male Female	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Sex: Female, Male Male	133 Participants n=93 Participants	65 Participants n=4 Participants	62 Participants n=27 Participants	260 Participants n=483 Participants
Region of Enrollment United States	133 participants n=93 Participants	65 participants n=4 Participants	62 participants n=27 Participants	260 participants n=483 Participants

PRIMARY outcome

Timeframe: Followed every 4 weeks from randomization until death, up to 7 years.

Outcome measures

Outcome measures
Measure	Induction Treatment + Strontium-89 n=65 Participants Induction treatment option 1 or induction treatment option 2. Randomization: Doxorubicin IV over 24 hours once weekly for 6 weeks + Strontium-89 IV once at beginning of chemotherapy.	Induction Treatment + No Strontium-89 n=62 Participants Induction treatment option 1 or induction treatment option 2. Randomization: Doxorubicin 20mg/m\^2 IV over 24 hours once weekly for 6 weeks.
Overall Survival From Randomization	24.2 months Interval 19.8 to 29.8	22.8 months Interval 17.7 to 27.7

SECONDARY outcome

Timeframe: Followed every 4 weeks from registration until death, up to 7 years.

Overall survival (OS) was computed using the number of months from the date of registration to the date of death. Participants still alive were censored at the last follow-up date. Kaplan-Meier methodology was used to evaluate OS.

Outcome measures

Outcome measures
Measure	Induction Treatment + Strontium-89 n=65 Participants Induction treatment option 1 or induction treatment option 2. Randomization: Doxorubicin IV over 24 hours once weekly for 6 weeks + Strontium-89 IV once at beginning of chemotherapy.	Induction Treatment + No Strontium-89 n=62 Participants Induction treatment option 1 or induction treatment option 2. Randomization: Doxorubicin 20mg/m\^2 IV over 24 hours once weekly for 6 weeks.
Overall Survival From Registration	27.9 months Interval 23.6 to 34.2	26.6 months Interval 21.1 to 32.2

Adverse Events

Induction Treatment

Serious events: 77 serious events

Other events: 34 other events

Deaths: 0 deaths

Induction Treatment + Strontium-89

Serious events: 53 serious events

Other events: 12 other events

Deaths: 0 deaths

Induction Treatment + No Strontium-89

Serious events: 47 serious events

Other events: 13 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Shi-Ming Tu, MD/Professor, Genitourinary Medical Oncology

University of Texas (UT) MD Anderson Cancer Center

Phone: 713-792-2830

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Serious adverse events
Measure	Induction Treatment n=138 participants at risk Induction treatment option 1 or induction treatment option 2.	Induction Treatment + Strontium-89 n=65 participants at risk Induction treatment option 1 or induction treatment option 2. Randomization: Doxorubicin IV over 24 hours once weekly for 6 weeks + Strontium-89 IV once at beginning of chemotherapy.	Induction Treatment + No Strontium-89 n=62 participants at risk Induction treatment option 1 or induction treatment option 2. Randomization: Doxorubicin 20mg/m\^2 IV over 24 hours once weekly for 6 weeks.
Infections and infestations Urinary Tract Infection	0.72% 1/138 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	1.5% 1/65 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	0.00% 0/62 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.
Infections and infestations Infection with Grade 3 or 4 Neutrophils	1.4% 2/138 • Number of events 2 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	0.00% 0/65 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	0.00% 0/62 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.
Musculoskeletal and connective tissue disorders Spinal Cord Compression	0.72% 1/138 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	0.00% 0/65 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	0.00% 0/62 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.
General disorders Death	55.8% 77/138 • Number of events 77 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	81.5% 53/65 • Number of events 53 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	75.8% 47/62 • Number of events 47 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.
Musculoskeletal and connective tissue disorders Musculoskeletal	0.00% 0/138 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	0.00% 0/65 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	1.6% 1/62 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.
Blood and lymphatic system disorders Neutrophil Count Decreased	0.72% 1/138 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	6.2% 4/65 • Number of events 4 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	0.00% 0/62 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.
General disorders Fever	0.72% 1/138 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	0.00% 0/65 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	0.00% 0/62 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.
Blood and lymphatic system disorders Hemoglobin Decreased	2.2% 3/138 • Number of events 3 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	0.00% 0/65 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	0.00% 0/62 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.
Metabolism and nutrition disorders Blood Glucose Increased	0.72% 1/138 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	0.00% 0/65 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	0.00% 0/62 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.
Gastrointestinal disorders Diarrhea	0.72% 1/138 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	0.00% 0/65 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	0.00% 0/62 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.
General disorders Fatigue	2.2% 3/138 • Number of events 3 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	1.5% 1/65 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	0.00% 0/62 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.
Infections and infestations Lymphopenia	1.4% 2/138 • Number of events 3 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	1.5% 1/65 • Number of events 3 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	1.6% 1/62 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.
Nervous system disorders Syncope	0.72% 1/138 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	0.00% 0/65 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	0.00% 0/62 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.
General disorders Pain	1.4% 2/138 • Number of events 2 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	1.5% 1/65 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	0.00% 0/62 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.
Vascular disorders Thrombosis	0.00% 0/138 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	1.5% 1/65 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	0.00% 0/62 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.
Infections and infestations Infection	0.72% 1/138 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	1.5% 1/65 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	0.00% 0/62 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.
Nervous system disorders Peripheral Motor Neuropathy	0.00% 0/138 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	1.5% 1/65 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	0.00% 0/62 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.
Metabolism and nutrition disorders Serum Phosphate Decreased	0.72% 1/138 • Number of events 2 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	0.00% 0/65 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	0.00% 0/62 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumor Pain	0.72% 1/138 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	0.00% 0/65 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	0.00% 0/62 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.
Metabolism and nutrition disorders Aspartate Aminotransferase Increased	0.72% 1/138 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	0.00% 0/65 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	0.00% 0/62 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.
Metabolism and nutrition disorders Alanine Aminotransferase Increased	0.72% 1/138 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	0.00% 0/65 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	0.00% 0/62 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.
Blood and lymphatic system disorders Leukopenia	0.00% 0/138 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	1.5% 1/65 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	0.00% 0/62 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.
Musculoskeletal and connective tissue disorders Bone Pain	1.4% 2/138 • Number of events 2 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	0.00% 0/65 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	0.00% 0/62 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.
Musculoskeletal and connective tissue disorders Pain in Extremity	0.72% 1/138 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	0.00% 0/65 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	0.00% 0/62 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.
Metabolism and nutrition disorders Serum Sodium Decreased	0.72% 1/138 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	0.00% 0/65 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	0.00% 0/62 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.
Nervous system disorders Depression	0.72% 1/138 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	0.00% 0/65 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	0.00% 0/62 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.
Psychiatric disorders Psychosis	0.72% 1/138 • Number of events 2 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	0.00% 0/65 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	0.00% 0/62 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.
Nervous system disorders Anxiety	0.72% 1/138 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	0.00% 0/65 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	0.00% 0/62 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.
Gastrointestinal disorders Rectal Pain	0.72% 1/138 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	0.00% 0/65 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	0.00% 0/62 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.
Cardiac disorders Hypertension	0.00% 0/138 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	1.5% 1/65 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	0.00% 0/62 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.
Renal and urinary disorders Urinary Retention	0.00% 0/138 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	1.5% 1/65 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	0.00% 0/62 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.
Metabolism and nutrition disorders Alkaline Phosphatase Increased	0.72% 1/138 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	0.00% 0/65 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	0.00% 0/62 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.
General disorders Constitutional Symptoms	0.72% 1/138 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	0.00% 0/65 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	0.00% 0/62 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.
Infections and infestations Sepsis	0.72% 1/138 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	0.00% 0/65 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	0.00% 0/62 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.

Other adverse events
Measure	Induction Treatment n=138 participants at risk Induction treatment option 1 or induction treatment option 2.	Induction Treatment + Strontium-89 n=65 participants at risk Induction treatment option 1 or induction treatment option 2. Randomization: Doxorubicin IV over 24 hours once weekly for 6 weeks + Strontium-89 IV once at beginning of chemotherapy.	Induction Treatment + No Strontium-89 n=62 participants at risk Induction treatment option 1 or induction treatment option 2. Randomization: Doxorubicin 20mg/m\^2 IV over 24 hours once weekly for 6 weeks.
Musculoskeletal and connective tissue disorders Bone Pain	2.9% 4/138 • Number of events 4 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	3.1% 2/65 • Number of events 2 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	3.2% 2/62 • Number of events 2 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.
Gastrointestinal disorders Nausea	8.0% 11/138 • Number of events 14 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	3.1% 2/65 • Number of events 2 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	8.1% 5/62 • Number of events 7 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.
Gastrointestinal disorders Vomiting	5.1% 7/138 • Number of events 9 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	0.00% 0/65 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	1.6% 1/62 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.
General disorders Fatigue	11.6% 16/138 • Number of events 18 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	16.9% 11/65 • Number of events 16 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	8.1% 5/62 • Number of events 5 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.
Respiratory, thoracic and mediastinal disorders Dyspnea	5.8% 8/138 • Number of events 8 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	3.1% 2/65 • Number of events 2 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	4.8% 3/62 • Number of events 3 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.
Blood and lymphatic system disorders Edema Limbs	5.8% 8/138 • Number of events 10 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	7.7% 5/65 • Number of events 6 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	3.2% 2/62 • Number of events 2 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/138 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	0.00% 0/65 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	1.6% 1/62 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.
Metabolism and nutrition disorders Alanine Aminotransferase Increased	0.72% 1/138 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	1.5% 1/65 • Number of events 4 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	1.6% 1/62 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.
Metabolism and nutrition disorders Bilirubin Increased	0.00% 0/138 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	0.00% 0/65 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	1.6% 1/62 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.
Metabolism and nutrition disorders Aspartate Aminotransferase Increased	3.6% 5/138 • Number of events 5 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	1.5% 1/65 • Number of events 2 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	1.6% 1/62 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.
Blood and lymphatic system disorders Neutrophil Count Decreased	0.72% 1/138 • Number of events 2 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	1.5% 1/65 • Number of events 2 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	1.6% 1/62 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.
Musculoskeletal and connective tissue disorders Pain in Extremity	2.9% 4/138 • Number of events 5 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	3.1% 2/65 • Number of events 3 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	4.8% 3/62 • Number of events 4 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.
Blood and lymphatic system disorders Platelet Count Decreased	1.4% 2/138 • Number of events 3 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	3.1% 2/65 • Number of events 2 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	1.6% 1/62 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.
Gastrointestinal disorders Mucositis Oral	0.72% 1/138 • Number of events 2 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	3.1% 2/65 • Number of events 3 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	1.6% 1/62 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.
Metabolism and nutrition disorders Serum Potassium Decreased	1.4% 2/138 • Number of events 2 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	1.5% 1/65 • Number of events 3 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	3.2% 2/62 • Number of events 2 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.
Metabolism and nutrition disorders Alkaline Phosphatase Increased	2.2% 3/138 • Number of events 6 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	1.5% 1/65 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	3.2% 2/62 • Number of events 2 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.
Gastrointestinal disorders Anorexia	4.3% 6/138 • Number of events 7 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	1.5% 1/65 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	1.6% 1/62 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.
General disorders Insomnia	3.6% 5/138 • Number of events 5 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	1.5% 1/65 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	1.6% 1/62 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.
Metabolism and nutrition disorders Blood Glucose Increased	4.3% 6/138 • Number of events 7 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	1.5% 1/65 • Number of events 3 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	1.6% 1/62 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.
Gastrointestinal disorders Diarrhea	3.6% 5/138 • Number of events 5 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	3.1% 2/65 • Number of events 2 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	1.6% 1/62 • Number of events 2 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.
Musculoskeletal and connective tissue disorders Back Pain	2.2% 3/138 • Number of events 3 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	3.1% 2/65 • Number of events 3 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	0.00% 0/62 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.
Metabolism and nutrition disorders Serum Sodium Decreased	1.4% 2/138 • Number of events 3 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	4.6% 3/65 • Number of events 8 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	0.00% 0/62 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.
Nervous system disorders Neurology (Other)	0.72% 1/138 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	1.5% 1/65 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	1.6% 1/62 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.
Skin and subcutaneous tissue disorders Dry Skin	0.72% 1/138 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	1.5% 1/65 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	0.00% 0/62 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.
Renal and urinary disorders Urinary Frequency	0.00% 0/138 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	1.5% 1/65 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	0.00% 0/62 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.
Skin and subcutaneous tissue disorders Alopecia	2.2% 3/138 • Number of events 3 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	0.00% 0/65 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	3.2% 2/62 • Number of events 2 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.
Nervous system disorders Peripheral Sensory Neuropathy	5.8% 8/138 • Number of events 8 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	3.1% 2/65 • Number of events 2 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	1.6% 1/62 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.
Blood and lymphatic system disorders Blood/Bone Marrow (Other)	0.72% 1/138 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	0.00% 0/65 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	1.6% 1/62 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.
Metabolism and nutrition disorders Serum Cacium Decreased	2.9% 4/138 • Number of events 8 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	1.5% 1/65 • Number of events 7 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	1.6% 1/62 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.
Blood and lymphatic system disorders Lymphopenia	1.4% 2/138 • Number of events 5 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	1.5% 1/65 • Number of events 10 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	1.6% 1/62 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.
Skin and subcutaneous tissue disorders Hypersensitivity	0.72% 1/138 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	1.5% 1/65 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	1.6% 1/62 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.
Skin and subcutaneous tissue disorders Rash Acneiform	0.00% 0/138 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	0.00% 0/65 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	1.6% 1/62 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.
Nervous system disorders Dizziness	1.4% 2/138 • Number of events 2 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	0.00% 0/65 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	1.6% 1/62 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.
Eye disorders Diplopia	0.00% 0/138 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	0.00% 0/65 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	1.6% 1/62 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.
Skin and subcutaneous tissue disorders Nail Disorder	0.00% 0/138 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	1.5% 1/65 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	1.6% 1/62 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.
Gastrointestinal disorders Gastritis	0.72% 1/138 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	1.5% 1/65 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	0.00% 0/62 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.
Gastrointestinal disorders Constipation	7.2% 10/138 • Number of events 10 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	4.6% 3/65 • Number of events 4 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	3.2% 2/62 • Number of events 2 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.
Metabolism and nutrition disorders Serum Albumin Decreased	2.9% 4/138 • Number of events 10 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	1.5% 1/65 • Number of events 4 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	0.00% 0/62 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.
Blood and lymphatic system disorders Leukopenia	0.72% 1/138 • Number of events 4 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	3.1% 2/65 • Number of events 7 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	1.6% 1/62 • Number of events 2 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.
Metabolism and nutrition disorders Creatinine Increased	0.72% 1/138 • Number of events 1 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	1.5% 1/65 • Number of events 4 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.	0.00% 0/62 • Adverse events (AEs) and serious adverse events (SAEs) were collected from administration of induction therapy to discontinuation of study drug. Overall collection period: June 2002 to July 2014.