Trial Outcomes & Findings for Hormone Therapy Plus Radiation Therapy With or Without Combination Chemotherapy in Treating Patients With Prostate Cancer (NCT NCT00004054)

Last Updated: 2020-10-22

Results Overview

Survival time is defined as time from randomization to date of death from any cause and is estimated by the Kaplan-Meier method. Patients last known to be alive are censored at date of last contact. This analysis was planned to occur when all patients had been potentially followed for 5 years.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

397 participants

Primary outcome timeframe

From the date of randomization to the date of death or last follow-up. Analysis occurs after all patients have been potentially followed for 5 years.

Results posted on

2020-10-22

Participant Flow

Participant milestones

Participant milestones
Measure	Hormones and RT Androgen suppression (AS) (Luteinizing hormone releasing hormone \[LHRH\] agonist and bicalutamide \[Casodex\] or flutamide \[Eulexin\]) x 8 weeks followed by RT to 70.2 Gy with concurrent AS (LHRH agonist and bicalutamide \[Casodex\] or flutamide \[Eulexin\]). AS will continue for a total of 24 months from initiation of all treatment. Oral anti-androgen will be discontinued at the end of radiation therapy (RT).	Hormones and RT Plus Chemotherapy AS (LHRH agonist and bicalutamide \[Casodex\] or flutamide \[Eulexin\]) x 8 weeks followed by RT to 70.2 Gy with concurrent AS (LHRH agonist and bicalutamide \[Casodex\] or flutamide \[Eulexin\]) and estramustine phosphate sodium, etoposide, paclitaxel, and warfarin \[Coumadin®\]. AS will continue for a total of 24 months from initiation all treatment. Oral antiandrogen will be discontinued at the end of RT.
Overall Study STARTED	197	200
Overall Study COMPLETED	197	200
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Hormone Therapy Plus Radiation Therapy With or Without Combination Chemotherapy in Treating Patients With Prostate Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Hormones and RT n=197 Participants Androgen suppression (AS) (Luteinizing hormone releasing hormone \[LHRH\] agonist and bicalutamide \[Casodex\] or flutamide \[Eulexin\]) x 8 weeks followed by RT to 70.2 Gy with concurrent AS (LHRH agonist and bicalutamide \[Casodex\] or flutamide \[Eulexin\]). AS will continue for a total of 24 months from initiation of all treatment. Oral anti-androgen will be discontinued at the end of radiation therapy (RT).	Hormones and RT Plus Chemotherapy n=200 Participants AS (LHRH agonist and bicalutamide \[Casodex\] or flutamide \[Eulexin\]) x 8 weeks followed by RT to 70.2 Gy with concurrent AS (LHRH agonist and bicalutamide \[Casodex\] or flutamide \[Eulexin\]) and estramustine phosphate sodium, etoposide, paclitaxel, and warfarin \[Coumadin®\]. AS will continue for a total of 24 months from initiation all treatment. Oral antiandrogen will be discontinued at the end of RT.	Total n=397 Participants Total of all reporting groups
Age, Continuous	65 years n=93 Participants	67 years n=4 Participants	66 years n=27 Participants
Sex: Female, Male Female	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Sex: Female, Male Male	197 Participants n=93 Participants	200 Participants n=4 Participants	397 Participants n=27 Participants

PRIMARY outcome

Timeframe: From the date of randomization to the date of death or last follow-up. Analysis occurs after all patients have been potentially followed for 5 years.

Population: All randomized patients.

Outcome measures

Outcome measures
Measure	Hormones and RT n=197 Participants Androgen suppression (AS) (Luteinizing hormone releasing hormone \[LHRH\] agonist and bicalutamide \[Casodex\] or flutamide \[Eulexin\]) x 8 weeks followed by RT to 70.2 Gy with concurrent AS (LHRH agonist and bicalutamide \[Casodex\] or flutamide \[Eulexin\]). AS will continue for a total of 24 months from initiation of all treatment. Oral anti-androgen will be discontinued at the end of radiation therapy (RT).	Hormones and RT Plus Chemotherapy n=200 Participants AS (LHRH agonist and bicalutamide \[Casodex\] or flutamide \[Eulexin\]) x 8 weeks followed by RT to 70.2 Gy with concurrent AS (LHRH agonist and bicalutamide \[Casodex\] or flutamide \[Eulexin\]) and estramustine phosphate sodium, etoposide, paclitaxel, and warfarin \[Coumadin®\]. AS will continue for a total of 24 months from initiation all treatment. Oral antiandrogen will be discontinued at the end of RT.
Overall Survival (5-year Rate Reported)	84.9 percentage of participants Interval 79.9 to 90.0	87.2 percentage of participants Interval 82.4 to 91.9

SECONDARY outcome

Timeframe: From randomization to last follow-up. Analysis occurs after all patients have been potentially followed for 5 years. Maximum follow-up at time of analysis was 13.3 years.

Population: All randomized patients

Biochemical failure uses the American Society for Radiation Oncology (ASTRO) definition of prostate-specific antigen (PSA) rises on three consecutive occasions, with biochemical failure date being midway between the last non-rising PSA and the first rise in PSA. Time to biochemical failure is defined as time from randomization to biochemical failure, last known follow-up (censored), or death (competing risk). Biochemical failure rates are estimated using the cumulative incidence method.

Outcome measures

Outcome measures
Measure	Hormones and RT n=197 Participants Androgen suppression (AS) (Luteinizing hormone releasing hormone \[LHRH\] agonist and bicalutamide \[Casodex\] or flutamide \[Eulexin\]) x 8 weeks followed by RT to 70.2 Gy with concurrent AS (LHRH agonist and bicalutamide \[Casodex\] or flutamide \[Eulexin\]). AS will continue for a total of 24 months from initiation of all treatment. Oral anti-androgen will be discontinued at the end of radiation therapy (RT).	Hormones and RT Plus Chemotherapy n=200 Participants AS (LHRH agonist and bicalutamide \[Casodex\] or flutamide \[Eulexin\]) x 8 weeks followed by RT to 70.2 Gy with concurrent AS (LHRH agonist and bicalutamide \[Casodex\] or flutamide \[Eulexin\]) and estramustine phosphate sodium, etoposide, paclitaxel, and warfarin \[Coumadin®\]. AS will continue for a total of 24 months from initiation all treatment. Oral antiandrogen will be discontinued at the end of RT.
Rate of Biochemical Failure at 5 Years	48.0 percentage of participants Interval 40.7 to 54.8	47.9 percentage of participants Interval 40.7 to 54.8

SECONDARY outcome

Timeframe: From randomization to last follow-up. Analysis occurs after all patients have been potentially followed for 5 years. Maximum follow-up at time of analysis was 13.3 years.

Population: All randomized patients

Local progression is defined as documented clinical local and/or regional progression. Time to local progression is defined as time from randomization to local progression, last known follow-up (censored), or death (competing risk). Local progression rates are estimated using the cumulative incidence method.

Outcome measures

Outcome measures
Measure	Hormones and RT n=197 Participants Androgen suppression (AS) (Luteinizing hormone releasing hormone \[LHRH\] agonist and bicalutamide \[Casodex\] or flutamide \[Eulexin\]) x 8 weeks followed by RT to 70.2 Gy with concurrent AS (LHRH agonist and bicalutamide \[Casodex\] or flutamide \[Eulexin\]). AS will continue for a total of 24 months from initiation of all treatment. Oral anti-androgen will be discontinued at the end of radiation therapy (RT).	Hormones and RT Plus Chemotherapy n=200 Participants AS (LHRH agonist and bicalutamide \[Casodex\] or flutamide \[Eulexin\]) x 8 weeks followed by RT to 70.2 Gy with concurrent AS (LHRH agonist and bicalutamide \[Casodex\] or flutamide \[Eulexin\]) and estramustine phosphate sodium, etoposide, paclitaxel, and warfarin \[Coumadin®\]. AS will continue for a total of 24 months from initiation all treatment. Oral antiandrogen will be discontinued at the end of RT.
Rate of Local Progression at 5 Years	5.8 percentage of participants Interval 3.1 to 9.7	4.1 percentage of participants Interval 1.9 to 7.6

SECONDARY outcome

Timeframe: From randomization to last follow-up. Analysis occurs after all patients have been potentially followed for 5 years. Maximum follow-up at time of analysis was 13.3 years.

Population: All randomized patients

Distant metastasis (DM) is defined as documented metastatic disease. Time to distant metastasis is defined as time from randomization to distant metastatic disease, last known follow-up (censored), or death (competing risk). Distant metastasis rates are estimated using the cumulative incidence method.

Outcome measures

Outcome measures
Measure	Hormones and RT n=197 Participants Androgen suppression (AS) (Luteinizing hormone releasing hormone \[LHRH\] agonist and bicalutamide \[Casodex\] or flutamide \[Eulexin\]) x 8 weeks followed by RT to 70.2 Gy with concurrent AS (LHRH agonist and bicalutamide \[Casodex\] or flutamide \[Eulexin\]). AS will continue for a total of 24 months from initiation of all treatment. Oral anti-androgen will be discontinued at the end of radiation therapy (RT).	Hormones and RT Plus Chemotherapy n=200 Participants AS (LHRH agonist and bicalutamide \[Casodex\] or flutamide \[Eulexin\]) x 8 weeks followed by RT to 70.2 Gy with concurrent AS (LHRH agonist and bicalutamide \[Casodex\] or flutamide \[Eulexin\]) and estramustine phosphate sodium, etoposide, paclitaxel, and warfarin \[Coumadin®\]. AS will continue for a total of 24 months from initiation all treatment. Oral antiandrogen will be discontinued at the end of RT.
Rate of Distant Metastasis at Five Years	10.4 percentage of participants Interval 6.6 to 15.2	8.3 percentage of participants Interval 4.9 to 12.7

SECONDARY outcome

Timeframe: From randomization to last follow-up. Analysis occurs after all patients have been potentially followed for 5 years. Maximum follow-up at time of analysis was 13.3 years.

Population: All randomized patients

Disease-free survival (DFS) was measured from the date of randomization to the date of documentation of progression (local, distant, biochemical failure), death, or last follow-up (censored). The Kaplan-Meier method was used to estimate DFS rates.

Outcome measures

Outcome measures
Measure	Hormones and RT n=197 Participants Androgen suppression (AS) (Luteinizing hormone releasing hormone \[LHRH\] agonist and bicalutamide \[Casodex\] or flutamide \[Eulexin\]) x 8 weeks followed by RT to 70.2 Gy with concurrent AS (LHRH agonist and bicalutamide \[Casodex\] or flutamide \[Eulexin\]). AS will continue for a total of 24 months from initiation of all treatment. Oral anti-androgen will be discontinued at the end of radiation therapy (RT).	Hormones and RT Plus Chemotherapy n=200 Participants AS (LHRH agonist and bicalutamide \[Casodex\] or flutamide \[Eulexin\]) x 8 weeks followed by RT to 70.2 Gy with concurrent AS (LHRH agonist and bicalutamide \[Casodex\] or flutamide \[Eulexin\]) and estramustine phosphate sodium, etoposide, paclitaxel, and warfarin \[Coumadin®\]. AS will continue for a total of 24 months from initiation all treatment. Oral antiandrogen will be discontinued at the end of RT.
Disease-free Survival Rate at 5 Years	39.1 percentage of participants Interval 32.2 to 46.0	42.9 percentage of participants Interval 35.9 to 49.9

Adverse Events

Hormones and RT

Serious events: 6 serious events

Other events: 189 other events

Deaths: 0 deaths

Hormones and RT Plus Chemotherapy

Serious events: 70 serious events

Other events: 198 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Wendy Seiferheld

NRG Oncology

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee PI's are required to abide by the sponsor's publication guidelines which require review by coauthors and subsequent review and approval by the sponsor.
Publication restrictions are in place

Restriction type: OTHER

Measure	Hormones and RT n=197 participants at risk AS (LHRH agonist and Casodex or Eulexin) x 8 weeks followed by RT to 70.2 Gy with concurrent AS (LHRH agonist and Casodex or Eulexin). Androgen suppression will continue for a total of 24 months from initiation of all treatment. Oral anti-androgen will be discontinued at the end of RT.	Hormones and RT Plus Chemotherapy n=200 participants at risk AS (LHRH agonist and Casodex or Eulexin) x 8 weeks followed by RT to 70.2 Gy with concurrent AS (LHRH agonist and Casodex or Eulexin) and chemotherapy. Androgen suppression will continue for a total of 24 months from initiation all treatment. Oral antiandrogen will be discontinued at the end of RT.
Blood and lymphatic system disorders Ferbrile neutropenia	0.00% 0/197 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	0.50% 1/200 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
Blood and lymphatic system disorders Hemoglobin decreased	0.00% 0/197 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	0.50% 1/200 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
Blood and lymphatic system disorders Packed red blood cell transfusion	0.00% 0/197 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	1.0% 2/200 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
Cardiac disorders Supraventricular arrhythmia NOS	0.00% 0/197 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	0.50% 1/200 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
Gastrointestinal disorders Abdominal pain NOS	0.00% 0/197 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	0.50% 1/200 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
Gastrointestinal disorders Diarrhea NOS	1.0% 2/197 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	5.5% 11/200 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
Gastrointestinal disorders Esophagitis NOS	0.00% 0/197 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	0.50% 1/200 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
Gastrointestinal disorders Late RT Toxicity: Bowel: NOS	0.00% 0/197 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	0.50% 1/200 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
Gastrointestinal disorders Nausea	0.00% 0/197 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	2.5% 5/200 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
Gastrointestinal disorders Proctitis NOS	1.0% 2/197 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	0.00% 0/200 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
Gastrointestinal disorders Stomatitis	0.00% 0/197 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	0.50% 1/200 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
Gastrointestinal disorders Vomiting NOS	0.00% 0/197 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	2.0% 4/200 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
General disorders Chest pain	0.00% 0/197 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	1.0% 2/200 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
General disorders Fatigue	0.00% 0/197 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	0.50% 1/200 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
General disorders Pain-other	0.00% 0/197 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	2.5% 5/200 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
Infections and infestations Infection NOS	0.00% 0/197 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	1.0% 2/200 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
Infections and infestations Infection with grade 3 or 4 neutropenia	0.00% 0/197 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	1.0% 2/200 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
Infections and infestations Infection, Other	0.00% 0/197 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	1.5% 3/200 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
Investigations Alanine aminotransferase increased	0.00% 0/197 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	0.50% 1/200 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
Investigations Aspartate aminotransferase increased	0.51% 1/197 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	0.00% 0/200 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
Investigations Blood bilirubin increased	0.00% 0/197 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	0.50% 1/200 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
Investigations Blood creatinine increased	0.51% 1/197 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	0.50% 1/200 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
Investigations Leukopenia NOS	0.00% 0/197 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	11.5% 23/200 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
Investigations Neutropenia	0.00% 0/197 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	13.5% 27/200 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
Investigations Platelet count decreased	0.00% 0/197 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	1.0% 2/200 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
Metabolism and nutrition disorders Dehydration	0.00% 0/197 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	1.5% 3/200 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
Metabolism and nutrition disorders Hyperglycemia NOS	0.00% 0/197 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	0.50% 1/200 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
Metabolism and nutrition disorders Hypocalcemia	0.00% 0/197 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	0.50% 1/200 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
Metabolism and nutrition disorders Hypokalemia	0.00% 0/197 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	1.0% 2/200 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Secondary malignancy, Other	0.00% 0/197 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	0.50% 1/200 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
Nervous system disorders Cerebral ischaemia	0.00% 0/197 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	0.50% 1/200 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
Renal and urinary disorders Hematuria present	0.00% 0/197 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	1.5% 3/200 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
Renal and urinary disorders Late RT Toxicity: Bladder: NOS	0.00% 0/197 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	1.0% 2/200 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
Renal and urinary disorders Urinary frequency	0.51% 1/197 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	0.00% 0/200 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
Respiratory, thoracic and mediastinal disorders Adult respiratory distress syndrome	0.00% 0/197 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	1.0% 2/200 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
Respiratory, thoracic and mediastinal disorders Dyspnea NOS	0.00% 0/197 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	2.5% 5/200 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
Respiratory, thoracic and mediastinal disorders Pulmonary-other	0.00% 0/197 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	1.5% 3/200 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).
Vascular disorders Thrombosis NOS	0.00% 0/197 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).	9.5% 19/200 Subjects experiencing more than one of a given serious adverse event (SAE) are counted only once for that SAE. The same methodology was applied for non-serious adverse events (AE).