Trial Outcomes & Findings for Thalidomide for the Treatment of Hormone-Dependent Prostate Cancer (NCT NCT00004635)

NCT ID: NCT00004635

Last Updated: 2018-05-22

Results Overview

Time to progression is defined as follows: if the PSA returns to baseline (defined as the PSA value prior to starting leuprolide or goserelin) or increases to the absolute value of 5 ng/ml.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 159 participants
• Primary outcome timeframe: 36 months
• Results posted on: 2018-05-22

Participant Flow

With nine institutions participating (NCI intramural, Columbia in NY, LSU in New Orleans, Wayne State Univ., Univ. of Washington, Univ. of Minnesota, Univ. of Pittsburgh, Holy Cross and Portsmouth Naval Hosp.)it is expected that 16 pts per mo (190 per year) can be entered onto the trial with an estimated completion of accrual expected in 18 months.

While patients are crossed-over to the other therapy, because the time until crossover is dependent on time until progression, this differs from a classic crossover study in which patients are followed on both arms for a fixed period of time, evaluated, given a wash-out period, and then followed identically on the other agent.

Participant milestones

Measure	Thalidomide Followed by Placebo Study participants are randomly assigned to one of two treatment groups. Participants received leuprolide or goserelin for 6 months. In period 1 participants received thalidomide orally 200 mg a day. Patients will be followed until PSA progression defined as prostate-specific antigen (PSA) level that returns to what it was before beginning leuprolide or goserelin or to 5 nanograms per liter, whichever is lower. The participants are returned to the leuprolide or goserelin treatment for 6 months. In period 2 participants received the placebo for thalidomide once a day.	Placebo Followed by Thalidomide Study participants are randomly assigned to one of two treatment groups. Participants received leuprolide or goserelin for 6 months. In period 1 participants received placebo for thalidomide. Patients will be followed until PSA progression defined as prostate-specific antigen (PSA) level that returns to what it was before beginning leuprolide or goserelin or to 5 nanograms per liter, whichever is lower. The participants are returned to the leuprolide or goserelin treatment for 6 months. In period 2 participants received thalidomide 200 mg once a day.
Period One STARTED	79	80
Period One Received Treatment	73	75
Period One COMPLETED	73	74
Period One NOT COMPLETED	6	6
Period Two STARTED	44	59
Period Two COMPLETED	38	50
Period Two NOT COMPLETED	6	9

Reasons for withdrawal

Measure	Thalidomide Followed by Placebo Study participants are randomly assigned to one of two treatment groups. Participants received leuprolide or goserelin for 6 months. In period 1 participants received thalidomide orally 200 mg a day. Patients will be followed until PSA progression defined as prostate-specific antigen (PSA) level that returns to what it was before beginning leuprolide or goserelin or to 5 nanograms per liter, whichever is lower. The participants are returned to the leuprolide or goserelin treatment for 6 months. In period 2 participants received the placebo for thalidomide once a day.	Placebo Followed by Thalidomide Study participants are randomly assigned to one of two treatment groups. Participants received leuprolide or goserelin for 6 months. In period 1 participants received placebo for thalidomide. Patients will be followed until PSA progression defined as prostate-specific antigen (PSA) level that returns to what it was before beginning leuprolide or goserelin or to 5 nanograms per liter, whichever is lower. The participants are returned to the leuprolide or goserelin treatment for 6 months. In period 2 participants received thalidomide 200 mg once a day.
Period One refused	2	1
Period One Withdrawal by Subject	1	1
Period One Protocol Violation	1	0
Period One PSA did not go <5 ng/mL	1	0
Period One second malignancy	1	0
Period One progressed	0	2
Period One health problem	0	1
Period One discrepancy in data entry	0	1
Period Two progression	2	3
Period Two Adverse Event	1	0
Period Two refused	0	2
Period Two health problem	1	1
Period Two travel issues	0	1
Period Two secondary malignancy	1	1
Period Two Lost to Follow-up	1	0
Period Two discrepancy in data entry	0	1

Baseline Characteristics

Thalidomide for the Treatment of Hormone-Dependent Prostate Cancer

Baseline characteristics by cohort

Measure	Thalidomide Followed by Placebo n=79 Participants Study participants are randomly assigned to one of two treatment groups. Participants received leuprolide or goserelin for 6 months. In period 1 participants received thalidomide orally 200 mg a day. Patients will be followed until PSA progression defined as prostate-specific antigen (PSA) level that returns to what it was before beginning leuprolide or goserelin or to 5 nanograms per liter, whichever is lower. The participants are returned to the leuprolide or goserelin treatment for 6 months. In period 2 participants received the placebo for thalidomide once a day.	Placebo Followed by Thalidomide n=80 Participants Study participants are randomly assigned to one of two treatment groups. Participants received leuprolide or goserelin for 6 months. In period 1 participants received placebo for thalidomide. Patients will be followed until PSA progression defined as prostate-specific antigen (PSA) level that returns to what it was before beginning leuprolide or goserelin or to 5 nanograms per liter, whichever is lower. The participants are returned to the leuprolide or goserelin treatment for 6 months. In period 2 participants received thalidomide 200 mg once a day.	Total n=159 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	41 Participants n=5 Participants	28 Participants n=7 Participants	69 Participants n=5 Participants
Age, Categorical >=65 years	38 Participants n=5 Participants	52 Participants n=7 Participants	90 Participants n=5 Participants
Age, Continuous	65.35 years STANDARD_DEVIATION 7.43 • n=5 Participants	68.46 years STANDARD_DEVIATION 8.54 • n=7 Participants	66.91 years STANDARD_DEVIATION 7.98 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	79 Participants n=5 Participants	80 Participants n=7 Participants	159 Participants n=5 Participants
Region of Enrollment United States	79 participants n=5 Participants	80 participants n=7 Participants	159 participants n=5 Participants

PRIMARY outcome

Timeframe: 36 months

Population: Per protocol. First intervention phase-73 participants (thalidomide) were analyzed and 0 was excluded; 74 participants were analyzed (placebo) and 1 was excluded for discrepancy in data entry. Crossover phase-50 participants were analyzed (thalidomide)and 1 was excluded for discrepancy in data entry, 38 participants for placebo and 0 excluded.

Time to progression is defined as follows: if the PSA returns to baseline (defined as the PSA value prior to starting leuprolide or goserelin) or increases to the absolute value of 5 ng/ml.

Outcome measures

Measure	Thalidomide n=123 Participants Participants who received thalidomide in period 1 or 2.	Placebo n=112 Participants Participants who received placebo in period 1 or 2
Time to Progression	15 months Interval 12.0 to 22.1	9.6 months Interval 8.5 to 12.9

SECONDARY outcome

Timeframe: Date treatment consent signed to date off study, approximately 60 months

Here are the total number of participants with adverse events. For the detailed list of adverse events see the adverse event module.

Outcome measures

Measure	Thalidomide n=138 Participants Participants who received thalidomide in period 1 or 2.	Placebo n=124 Participants Participants who received placebo in period 1 or 2
The Number of Participants With Adverse Events	117 Participants	98 Participants

Adverse Events

Thalidomide

Serious events: 117 serious events

Other events: 67 other events

Deaths: 0 deaths

Placebo

Serious events: 98 serious events

Other events: 63 other events

Deaths: 0 deaths

Goserelin (Zoladex)

Serious events: 13 serious events

Other events: 10 other events

Deaths: 0 deaths

Leuprolide

Serious events: 124 serious events

Other events: 66 other events

Deaths: 0 deaths

Serious adverse events

Measure	Thalidomide n=138 participants at risk	Placebo n=124 participants at risk	Goserelin (Zoladex) n=159 participants at risk	Leuprolide n=159 participants at risk
Gastrointestinal disorders Dry mouth	0.72% 1/138 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Cardiac disorders Ventricular arrhythmia (PVCs/bigeminy/trigeminy/ventricular tachycardia)	0.72% 1/138 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Eye disorders Vision-blurred vision	5.8% 8/138 • Number of events 9 • Date treatment consent signed to date off study, approximately 5 years.	2.4% 3/124 • Number of events 3 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.
Eye disorders Vision-double vision (diplopia)	0.72% 1/138 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	1.6% 2/124 • Number of events 3 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Eye disorders Vision-flashing lights/floaters	1.4% 2/138 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.	0.81% 1/124 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Eye disorders Vision-night blindness (nyctalopia)	0.72% 1/138 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Respiratory, thoracic and mediastinal disorders Voice changes/stridor/larynx (e.g., hoarsneness, loss of voice, laryngitis)	0.72% 1/138 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	1.6% 2/124 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Endocrine disorders Endocrine-Other	1.4% 2/138 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Reproductive system and breast disorders Impotency	0.00% 0/138 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.
Gastrointestinal disorders Vomiting	2.9% 4/138 • Number of events 4 • Date treatment consent signed to date off study, approximately 5 years.	2.4% 3/124 • Number of events 3 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Investigations Weight gain	6.5% 9/138 • Number of events 11 • Date treatment consent signed to date off study, approximately 5 years.	2.4% 3/124 • Number of events 4 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.
Investigations Weight loss	1.4% 2/138 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Infections and infestations Wound-infectious	0.72% 1/138 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Respiratory, thoracic and mediastinal disorders Pleuritic pain	0.00% 0/138 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.
Respiratory, thoracic and mediastinal disorders Pneumonitis/pulmonary infiltrates	0.00% 0/138 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.
Investigations LDH	0.72% 1/138 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Metabolism and nutrition disorders Metabolic-Other	0.72% 1/138 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Nervous system disorders Neuropathic pain (e.g., jaw pain, neurologic pain, phantom limb pain, post-infectious neuralgia, or	0.72% 1/138 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Renal and urinary disorders Renal/GU-Other	2.9% 4/138 • Number of events 5 • Date treatment consent signed to date off study, approximately 5 years.	3.2% 4/124 • Number of events 5 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Cardiac disorders Sinus tachycardia	0.72% 1/138 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.
Skin and subcutaneous tissue disorders Sweating (diaphoresis)	1.4% 2/138 • Number of events 3 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	2.5% 4/159 • Number of events 6 • Date treatment consent signed to date off study, approximately 5 years.
Cardiac disorders Cardiac-ischemia/infarction	1.4% 2/138 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.	0.81% 1/124 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	1.3% 2/159 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.
Cardiac disorders Cardiac-left ventricular function	0.72% 1/138 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Gastrointestinal disorders Colitis	0.72% 1/138 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Immune system disorders Allergic reaction/hypersensitivity (including drug fever)	0.72% 1/138 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Reproductive system and breast disorders Abdominal pain or cramping	3.6% 5/138 • Number of events 5 • Date treatment consent signed to date off study, approximately 5 years.	1.6% 2/124 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Investigations Alkaline phosphatase	1.4% 2/138 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.	3.2% 4/124 • Number of events 5 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	2.5% 4/159 • Number of events 4 • Date treatment consent signed to date off study, approximately 5 years.
Immune system disorders Allergic rhinitis (including sneezing, nasal stuffiness, postnasal drip)	2.2% 3/138 • Number of events 3 • Date treatment consent signed to date off study, approximately 5 years.	1.6% 2/124 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.
General disorders Chest pain (non-cardiac and non-pleuritis)	3.6% 5/138 • Number of events 5 • Date treatment consent signed to date off study, approximately 5 years.	0.81% 1/124 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Skin and subcutaneous tissue disorders Alopecia	3.6% 5/138 • Number of events 5 • Date treatment consent signed to date off study, approximately 5 years.	0.81% 1/124 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Gastrointestinal disorders Anorexia	2.2% 3/138 • Number of events 4 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.
Cardiac disorders Arrhythmia-other	1.4% 2/138 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Musculoskeletal and connective tissue disorders Arthralgia (joint pain)	3.6% 5/138 • Number of events 5 • Date treatment consent signed to date off study, approximately 5 years.	4.0% 5/124 • Number of events 5 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	1.9% 3/159 • Number of events 4 • Date treatment consent signed to date off study, approximately 5 years.
Musculoskeletal and connective tissue disorders Arthritis	0.72% 1/138 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.
Nervous system disorders Ataxia (incoordination)	8.7% 12/138 • Number of events 14 • Date treatment consent signed to date off study, approximately 5 years.	0.81% 1/124 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.
Investigations Bilirubin	5.8% 8/138 • Number of events 11 • Date treatment consent signed to date off study, approximately 5 years.	12.9% 16/124 • Number of events 22 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	2.5% 4/159 • Number of events 4 • Date treatment consent signed to date off study, approximately 5 years.
Blood and lymphatic system disorders Brusing (in absence of grade 3 or 4 thrombocytopenia)	1.4% 2/138 • Number of events 3 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Nervous system disorders CNS cerebrovascular ischemia	2.2% 3/138 • Number of events 3 • Date treatment consent signed to date off study, approximately 5 years.	0.81% 1/124 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.
Investigations CPK (creatine phosphokinase)	2.9% 4/138 • Number of events 5 • Date treatment consent signed to date off study, approximately 5 years.	4.0% 5/124 • Number of events 5 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.
Cardiac disorders Circulatory or cardiac-Other	2.2% 3/138 • Number of events 3 • Date treatment consent signed to date off study, approximately 5 years.	1.6% 2/124 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Nervous system disorders Cognitive disturbance/learning problems	2.2% 3/138 • Number of events 5 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Psychiatric disorders Confusion	5.8% 8/138 • Number of events 8 • Date treatment consent signed to date off study, approximately 5 years.	1.6% 2/124 • Number of events 3 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Gastrointestinal disorders Constipation	61.6% 85/138 • Number of events 116 • Date treatment consent signed to date off study, approximately 5 years.	25.8% 32/124 • Number of events 42 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	1.9% 3/159 • Number of events 3 • Date treatment consent signed to date off study, approximately 5 years.
Musculoskeletal and connective tissue disorders Bone pain	3.6% 5/138 • Number of events 7 • Date treatment consent signed to date off study, approximately 5 years.	0.81% 1/124 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
General disorders Constitutional symptoms-Other	1.4% 2/138 • Number of events 4 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.
Respiratory, thoracic and mediastinal disorders Cough	2.9% 4/138 • Number of events 4 • Date treatment consent signed to date off study, approximately 5 years.	6.5% 8/124 • Number of events 8 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.
Investigations Creatinine	2.9% 4/138 • Number of events 5 • Date treatment consent signed to date off study, approximately 5 years.	3.2% 4/124 • Number of events 5 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	2.5% 4/159 • Number of events 4 • Date treatment consent signed to date off study, approximately 5 years.
Nervous system disorders Depressed level of consciousness	23.9% 33/138 • Number of events 38 • Date treatment consent signed to date off study, approximately 5 years.	4.0% 5/124 • Number of events 5 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	1.3% 2/159 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.
Skin and subcutaneous tissue disorders Derma/Skin-Other: Lower lip lesion	0.72% 1/138 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Gastrointestinal disorders Diarrhea (without colostomy)	5.8% 8/138 • Number of events 8 • Date treatment consent signed to date off study, approximately 5 years.	6.5% 8/124 • Number of events 8 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	1.9% 3/159 • Number of events 3 • Date treatment consent signed to date off study, approximately 5 years.
Nervous system disorders Dizziness/lightheadedness	42.0% 58/138 • Number of events 67 • Date treatment consent signed to date off study, approximately 5 years.	14.5% 18/124 • Number of events 22 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	1.3% 2/159 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.
Eye disorders Dry eye	4.3% 6/138 • Number of events 6 • Date treatment consent signed to date off study, approximately 5 years.	1.6% 2/124 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Skin and subcutaneous tissue disorders Dry skin	12.3% 17/138 • Number of events 19 • Date treatment consent signed to date off study, approximately 5 years.	4.0% 5/124 • Number of events 5 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Gastrointestinal disorders Dyspepsia/heartburn	2.9% 4/138 • Number of events 4 • Date treatment consent signed to date off study, approximately 5 years.	4.0% 5/124 • Number of events 5 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Gastrointestinal disorders Dysphagia, esophagitis, odynophagia (painful swallowing)	1.4% 2/138 • Number of events 3 • Date treatment consent signed to date off study, approximately 5 years.	0.81% 1/124 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Respiratory, thoracic and mediastinal disorders Dyspnea (shortness of breath)	26.1% 36/138 • Number of events 42 • Date treatment consent signed to date off study, approximately 5 years.	10.5% 13/124 • Number of events 16 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	1.3% 2/159 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.
Renal and urinary disorders Dysuria (painful urination)	0.72% 1/138 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
General disorders Edema	28.3% 39/138 • Number of events 50 • Date treatment consent signed to date off study, approximately 5 years.	8.9% 11/124 • Number of events 13 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	1.9% 3/159 • Number of events 3 • Date treatment consent signed to date off study, approximately 5 years.
Reproductive system and breast disorders Erectile impotence	0.72% 1/138 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	6.9% 11/159 • Number of events 11 • Date treatment consent signed to date off study, approximately 5 years.
Musculoskeletal and connective tissue disorders Extrapyramidal/involuntary movement/restlessness	0.72% 1/138 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
General disorders Fatigue (lethargy, malaise, asthenia)	47.8% 66/138 • Number of events 91 • Date treatment consent signed to date off study, approximately 5 years.	29.8% 37/124 • Number of events 47 • Date treatment consent signed to date off study, approximately 5 years.	2.5% 4/159 • Number of events 5 • Date treatment consent signed to date off study, approximately 5 years.	13.2% 21/159 • Number of events 22 • Date treatment consent signed to date off study, approximately 5 years.
General disorders Fever (in absence of neutropenia, where neutropenia is defined as AGC<1.0x109/L)	0.72% 1/138 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.
Gastrointestinal disorders Flatulence	0.72% 1/138 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	3.2% 4/124 • Number of events 4 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Vascular disorders Flushing	1.4% 2/138 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.
Gastrointestinal disorders GI-Other	2.9% 4/138 • Number of events 4 • Date treatment consent signed to date off study, approximately 5 years.	2.4% 3/124 • Number of events 4 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Gastrointestinal disorders Gastritis	0.72% 1/138 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	1.6% 2/124 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Reproductive system and breast disorders Gynecomastia	5.1% 7/138 • Number of events 7 • Date treatment consent signed to date off study, approximately 5 years.	3.2% 4/124 • Number of events 4 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	1.9% 3/159 • Number of events 3 • Date treatment consent signed to date off study, approximately 5 years.
Nervous system disorders Headache	18.1% 25/138 • Number of events 28 • Date treatment consent signed to date off study, approximately 5 years.	10.5% 13/124 • Number of events 13 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	2.5% 4/159 • Number of events 5 • Date treatment consent signed to date off study, approximately 5 years.
Ear and labyrinth disorders Hearing-Other	2.2% 3/138 • Number of events 3 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Blood and lymphatic system disorders Hematologic-Other	0.72% 1/138 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	2.4% 3/124 • Number of events 5 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	3.1% 5/159 • Number of events 5 • Date treatment consent signed to date off study, approximately 5 years.
Renal and urinary disorders Hematuria (in the absence of vaginal bleeding)	1.4% 2/138 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.	1.6% 2/124 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.
Investigations Hemoglobin (Hgb)	15.2% 21/138 • Number of events 25 • Date treatment consent signed to date off study, approximately 5 years.	6.5% 8/124 • Number of events 13 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	5.0% 8/159 • Number of events 8 • Date treatment consent signed to date off study, approximately 5 years.
Blood and lymphatic system disorders Hemolysis (e.g., immune hemolytic anemia, drug-related hemolysis, other	0.72% 1/138 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Respiratory, thoracic and mediastinal disorders Hiccoughs (hiccups, singultus)	0.72% 1/138 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Vascular disorders Hot flashes/flashes	8.0% 11/138 • Number of events 11 • Date treatment consent signed to date off study, approximately 5 years.	7.3% 9/124 • Number of events 13 • Date treatment consent signed to date off study, approximately 5 years.	6.9% 11/159 • Number of events 13 • Date treatment consent signed to date off study, approximately 5 years.	64.2% 102/159 • Number of events 130 • Date treatment consent signed to date off study, approximately 5 years.
Metabolism and nutrition disorders Hypercalcemia	2.2% 3/138 • Number of events 3 • Date treatment consent signed to date off study, approximately 5 years.	2.4% 3/124 • Number of events 3 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	1.9% 3/159 • Number of events 3 • Date treatment consent signed to date off study, approximately 5 years.
Metabolism and nutrition disorders Hyperglycemia	21.7% 30/138 • Number of events 48 • Date treatment consent signed to date off study, approximately 5 years.	19.4% 24/124 • Number of events 27 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	6.3% 10/159 • Number of events 11 • Date treatment consent signed to date off study, approximately 5 years.
Metabolism and nutrition disorders Hyperkalemia	2.9% 4/138 • Number of events 9 • Date treatment consent signed to date off study, approximately 5 years.	4.8% 6/124 • Number of events 8 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.
Metabolism and nutrition disorders Hypermagnesemia	1.4% 2/138 • Number of events 3 • Date treatment consent signed to date off study, approximately 5 years.	3.2% 4/124 • Number of events 4 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	1.9% 3/159 • Number of events 3 • Date treatment consent signed to date off study, approximately 5 years.
Metabolism and nutrition disorders Hypernatremia	2.9% 4/138 • Number of events 4 • Date treatment consent signed to date off study, approximately 5 years.	2.4% 3/124 • Number of events 3 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Vascular disorders Hypertension	3.6% 5/138 • Number of events 6 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	1.3% 2/159 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.
Metabolism and nutrition disorders Hypoalbuminemia	17.4% 24/138 • Number of events 30 • Date treatment consent signed to date off study, approximately 5 years.	12.1% 15/124 • Number of events 26 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	5.7% 9/159 • Number of events 9 • Date treatment consent signed to date off study, approximately 5 years.
Metabolism and nutrition disorders Hypoglycemia	1.4% 2/138 • Number of events 3 • Date treatment consent signed to date off study, approximately 5 years.	3.2% 4/124 • Number of events 6 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Metabolism and nutrition disorders Hypokalemia	1.4% 2/138 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.	1.6% 2/124 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Metabolism and nutrition disorders Hypomagnesmia	10.9% 15/138 • Number of events 16 • Date treatment consent signed to date off study, approximately 5 years.	3.2% 4/124 • Number of events 4 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.
Metabolism and nutrition disorders Hyponatremia	2.9% 4/138 • Number of events 4 • Date treatment consent signed to date off study, approximately 5 years.	2.4% 3/124 • Number of events 4 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.
Metabolism and nutrition disorders Hypophosphatemia	3.6% 5/138 • Number of events 7 • Date treatment consent signed to date off study, approximately 5 years.	2.4% 3/124 • Number of events 4 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.
Vascular disorders Hypotension	6.5% 9/138 • Number of events 9 • Date treatment consent signed to date off study, approximately 5 years.	3.2% 4/124 • Number of events 4 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Endocrine disorders Hypothyroidism	2.2% 3/138 • Number of events 3 • Date treatment consent signed to date off study, approximately 5 years.	0.81% 1/124 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Renal and urinary disorders Incontinence	5.1% 7/138 • Number of events 7 • Date treatment consent signed to date off study, approximately 5 years.	1.6% 2/124 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	1.3% 2/159 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.
Infections and infestations Infection without neutropenia	5.8% 8/138 • Number of events 13 • Date treatment consent signed to date off study, approximately 5 years.	7.3% 9/124 • Number of events 14 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.
Infections and infestations Infection, Other	2.2% 3/138 • Number of events 3 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Ear and labyrinth disorders Inner ear/hearing	1.4% 2/138 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.	0.81% 1/124 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Psychiatric disorders Insomnia	0.72% 1/138 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	8.9% 11/124 • Number of events 12 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	3.1% 5/159 • Number of events 6 • Date treatment consent signed to date off study, approximately 5 years.
Musculoskeletal and connective tissue disorders Joint, muscle, or bone (osseous)-Other	4.3% 6/138 • Number of events 7 • Date treatment consent signed to date off study, approximately 5 years.	3.2% 4/124 • Number of events 9 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Investigations Leukocytes (total WBC)	9.4% 13/138 • Number of events 23 • Date treatment consent signed to date off study, approximately 5 years.	3.2% 4/124 • Number of events 19 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	1.3% 2/159 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.
Psychiatric disorders Libido	1.4% 2/138 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	8.2% 13/159 • Number of events 14 • Date treatment consent signed to date off study, approximately 5 years.
Blood and lymphatic system disorders Lymphatics	1.4% 2/138 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Blood and lymphatic system disorders Lymphopenia	5.1% 7/138 • Number of events 12 • Date treatment consent signed to date off study, approximately 5 years.	3.2% 4/124 • Number of events 5 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.
Nervous system disorders Memory loss	6.5% 9/138 • Number of events 9 • Date treatment consent signed to date off study, approximately 5 years.	2.4% 3/124 • Number of events 3 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Psychiatric disorders Mood alteration-anxiety agitation	8.0% 11/138 • Number of events 12 • Date treatment consent signed to date off study, approximately 5 years.	2.4% 3/124 • Number of events 3 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.
Psychiatric disorders Mood alteration-depression	8.0% 11/138 • Number of events 11 • Date treatment consent signed to date off study, approximately 5 years.	4.0% 5/124 • Number of events 5 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	1.9% 3/159 • Number of events 3 • Date treatment consent signed to date off study, approximately 5 years.
Gastrointestinal disorders Mouth dryness	31.9% 44/138 • Number of events 45 • Date treatment consent signed to date off study, approximately 5 years.	10.5% 13/124 • Number of events 15 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Musculoskeletal and connective tissue disorders Muscle cramps (thigh)	0.72% 1/138 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Musculoskeletal and connective tissue disorders Muscle weakness (not due to neuropathy)	7.2% 10/138 • Number of events 11 • Date treatment consent signed to date off study, approximately 5 years.	0.81% 1/124 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.
Musculoskeletal and connective tissue disorders Myalgia (muscle ache)	14.5% 20/138 • Number of events 20 • Date treatment consent signed to date off study, approximately 5 years.	8.9% 11/124 • Number of events 13 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	2.5% 4/159 • Number of events 4 • Date treatment consent signed to date off study, approximately 5 years.
Skin and subcutaneous tissue disorders Nail changes	0.72% 1/138 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	1.6% 2/124 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Gastrointestinal disorders Nausea	10.9% 15/138 • Number of events 20 • Date treatment consent signed to date off study, approximately 5 years.	8.1% 10/124 • Number of events 11 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.
Nervous system disorders Neurologic-Other	5.1% 7/138 • Number of events 8 • Date treatment consent signed to date off study, approximately 5 years.	1.6% 2/124 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.
Nervous system disorders Neuropathy cranial	2.9% 4/138 • Number of events 6 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Nervous system disorders Neuropathy motor	5.8% 8/138 • Number of events 9 • Date treatment consent signed to date off study, approximately 5 years.	0.81% 1/124 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Nervous system disorders Neuropathy-sensory	39.9% 55/138 • Number of events 93 • Date treatment consent signed to date off study, approximately 5 years.	18.5% 23/124 • Number of events 31 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	3.8% 6/159 • Number of events 6 • Date treatment consent signed to date off study, approximately 5 years.
Investigations Neutrophils/granulocytes (ANC/AGC)	6.5% 9/138 • Number of events 18 • Date treatment consent signed to date off study, approximately 5 years.	3.2% 4/124 • Number of events 9 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Eye disorders Ocular-Other	2.2% 3/138 • Number of events 3 • Date treatment consent signed to date off study, approximately 5 years.	0.81% 1/124 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Nervous system disorders Pain-Other	3.6% 5/138 • Number of events 5 • Date treatment consent signed to date off study, approximately 5 years.	4.8% 6/124 • Number of events 8 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	2.5% 4/159 • Number of events 4 • Date treatment consent signed to date off study, approximately 5 years.
Cardiac disorders Palpitation	0.72% 1/138 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Blood and lymphatic system disorders Petechiae/purpura (hemorrhage/bleeding into skin or mucosa)	0.72% 1/138 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.81% 1/124 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Skin and subcutaneous tissue disorders Photosensitivity	0.72% 1/138 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.81% 1/124 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Investigations Platelets	2.2% 3/138 • Number of events 3 • Date treatment consent signed to date off study, approximately 5 years.	3.2% 4/124 • Number of events 6 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	1.9% 3/159 • Number of events 3 • Date treatment consent signed to date off study, approximately 5 years.
Investigations Protrombin Time/INR-International Normalized Ratio of protrombin time	0.72% 1/138 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Skin and subcutaneous tissue disorders Pruritus	0.72% 1/138 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	2.4% 3/124 • Number of events 4 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.
Respiratory, thoracic and mediastinal disorders Pulmonary-Other	4.3% 6/138 • Number of events 6 • Date treatment consent signed to date off study, approximately 5 years.	1.6% 2/124 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.
Skin and subcutaneous tissue disorders Rash/desquamation	18.8% 26/138 • Number of events 30 • Date treatment consent signed to date off study, approximately 5 years.	11.3% 14/124 • Number of events 16 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	1.9% 3/159 • Number of events 3 • Date treatment consent signed to date off study, approximately 5 years.
Gastrointestinal disorders Rectal bleeding/hematochezia	0.72% 1/138 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	4.8% 6/124 • Number of events 7 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.
Gastrointestinal disorders Rectal or perirectal pain (proctalgia)	1.4% 2/138 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.	0.81% 1/124 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Investigations SGOT (AST)	7.2% 10/138 • Number of events 12 • Date treatment consent signed to date off study, approximately 5 years.	12.9% 16/124 • Number of events 23 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	7.5% 12/159 • Number of events 14 • Date treatment consent signed to date off study, approximately 5 years.
Investigations SGPT (ALT)	6.5% 9/138 • Number of events 11 • Date treatment consent signed to date off study, approximately 5 years.	9.7% 12/124 • Number of events 16 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	10.1% 16/159 • Number of events 18 • Date treatment consent signed to date off study, approximately 5 years.
Gastrointestinal disorders Salivary gland changes	1.4% 2/138 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.	0.81% 1/124 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Secondary Malignancy-Other	0.72% 1/138 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	1.6% 2/124 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Nervous system disorders Sense of smell	1.4% 2/138 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.
Cardiac disorders Sinus bradycardia	20.3% 28/138 • Number of events 31 • Date treatment consent signed to date off study, approximately 5 years.	4.0% 5/124 • Number of events 5 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.
Skin and subcutaneous tissue disorders Skin-Other	2.2% 3/138 • Number of events 3 • Date treatment consent signed to date off study, approximately 5 years.	4.0% 5/124 • Number of events 5 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.
Gastrointestinal disorders Stomatitis/pharyngitis (oral/pharyngeal mucositis)	1.4% 2/138 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Cardiac disorders Supraventricular arrhythmias (SVT/atrial fibrillation/flutter)	1.4% 2/138 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.	1.6% 2/124 • Number of events 3 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.
Nervous system disorders Syncope	2.9% 4/138 • Number of events 6 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Gastrointestinal disorders Taste disturbance (dysgeusia)	2.9% 4/138 • Number of events 4 • Date treatment consent signed to date off study, approximately 5 years.	2.4% 3/124 • Number of events 3 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Eye disorders Tearing (watery eyes)	2.2% 3/138 • Number of events 3 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.
Vascular disorders Thrombosis/embolism	1.4% 2/138 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.	0.81% 1/124 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.
Nervous system disorders Tremor	13.0% 18/138 • Number of events 19 • Date treatment consent signed to date off study, approximately 5 years.	2.4% 3/124 • Number of events 4 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Renal and urinary disorders Urinary frequency/urgency	1.4% 2/138 • Number of events 3 • Date treatment consent signed to date off study, approximately 5 years.	3.2% 4/124 • Number of events 4 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	5.0% 8/159 • Number of events 8 • Date treatment consent signed to date off study, approximately 5 years.
Skin and subcutaneous tissue disorders Urticaria (hives, welts, wheals)	0.72% 1/138 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.81% 1/124 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Gastrointestinal disorders Pancreatitis	0.72% 1/138 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Respiratory, thoracic and mediastinal disorders Pleural effusion (non-malignant)	0.00% 0/138 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.
General disorders Rigors/chills	0.72% 1/138 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Investigations Hypercholesterolemia	0.00% 0/138 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.
Eye disorders Vision-photophobia	0.72% 1/138 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Metabolism and nutrition disorders Hypocalcemia	0.72% 1/138 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Nervous system disorders Seizure(s)	0.72% 1/138 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Nervous system disorders Vasovagal episode	0.72% 1/138 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Ear and labyrinth disorders Vertigo	1.4% 2/138 • Number of events 4 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.

Other adverse events

Measure	Thalidomide n=138 participants at risk	Placebo n=124 participants at risk	Goserelin (Zoladex) n=159 participants at risk	Leuprolide n=159 participants at risk
Immune system disorders Allergic rhinitis (including sneezing, nasal stuffiness, postnasal drip)	1.4% 2/138 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.	0.81% 1/124 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Reproductive system and breast disorders Abdominal pain or cramping	1.4% 2/138 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.	2.4% 3/124 • Number of events 3 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Investigations Alkaline phosphatase	1.4% 2/138 • Number of events 3 • Date treatment consent signed to date off study, approximately 5 years.	0.81% 1/124 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	1.9% 3/159 • Number of events 3 • Date treatment consent signed to date off study, approximately 5 years.
Musculoskeletal and connective tissue disorders Bone pain	1.4% 2/138 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.	0.81% 1/124 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Cardiac disorders Cardiac left ventricular function	0.72% 1/138 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Cardiac disorders Cardiac-ischemia/infarction	0.72% 1/138 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.
Eye disorders Cataract	0.72% 1/138 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Cardiac disorders Circulatory or cardiac-Other	2.2% 3/138 • Number of events 3 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Endocrine disorders Endocrine-Other	0.72% 1/138 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Blood and lymphatic system disorders Coag-Other	0.72% 1/138 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Respiratory, thoracic and mediastinal disorders Cough	2.2% 3/138 • Number of events 4 • Date treatment consent signed to date off study, approximately 5 years.	1.6% 2/124 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Investigations Creatinine	6.5% 9/138 • Number of events 11 • Date treatment consent signed to date off study, approximately 5 years.	4.0% 5/124 • Number of events 7 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.
Metabolism and nutrition disorders Dehydration	0.72% 1/138 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.81% 1/124 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Nervous system disorders Dizziness/lightheadedness	0.72% 1/138 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	1.9% 3/159 • Number of events 4 • Date treatment consent signed to date off study, approximately 5 years.
Skin and subcutaneous tissue disorders Dry skin	0.72% 1/138 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Gastrointestinal disorders Dyspepsia/heartburn	0.72% 1/138 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Respiratory, thoracic and mediastinal disorders Dyspnea (shortness of breath)	0.72% 1/138 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	3.2% 4/124 • Number of events 4 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.
General disorders Fatigue (lethargy, malaise, asthenia)	1.4% 2/138 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.	0.81% 1/124 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.	1.9% 3/159 • Number of events 3 • Date treatment consent signed to date off study, approximately 5 years.
Nervous system disorders Headache	1.4% 2/138 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.	0.81% 1/124 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	1.3% 2/159 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.
Ear and labyrinth disorders Hearing-Other	1.4% 2/138 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Renal and urinary disorders Hematuria (in the absence of vaginal bleeding)	0.72% 1/138 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.81% 1/124 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.
Blood and lymphatic system disorders Hemoglobin (Hgb)	2.2% 3/138 • Number of events 3 • Date treatment consent signed to date off study, approximately 5 years.	2.4% 3/124 • Number of events 4 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	3.8% 6/159 • Number of events 8 • Date treatment consent signed to date off study, approximately 5 years.
Metabolism and nutrition disorders Hypercalcemia	2.2% 3/138 • Number of events 3 • Date treatment consent signed to date off study, approximately 5 years.	3.2% 4/124 • Number of events 4 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	1.9% 3/159 • Number of events 3 • Date treatment consent signed to date off study, approximately 5 years.
Metabolism and nutrition disorders Hyperglycemia	8.7% 12/138 • Number of events 17 • Date treatment consent signed to date off study, approximately 5 years.	10.5% 13/124 • Number of events 23 • Date treatment consent signed to date off study, approximately 5 years.	1.9% 3/159 • Number of events 3 • Date treatment consent signed to date off study, approximately 5 years.	8.2% 13/159 • Number of events 14 • Date treatment consent signed to date off study, approximately 5 years.
Metabolism and nutrition disorders Hyperkalemia	2.9% 4/138 • Number of events 4 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.
Metabolism and nutrition disorders Hypermagnesemia	1.4% 2/138 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.	1.6% 2/124 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.
Metabolism and nutrition disorders Hypernatremia	0.72% 1/138 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Vascular disorders Hypertension	2.2% 3/138 • Number of events 3 • Date treatment consent signed to date off study, approximately 5 years.	2.4% 3/124 • Number of events 3 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	1.3% 2/159 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.
Metabolism and nutrition disorders Hypertriglyceridemia	0.72% 1/138 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Metabolism and nutrition disorders Hyperuricemia	1.4% 2/138 • Number of events 4 • Date treatment consent signed to date off study, approximately 5 years.	4.8% 6/124 • Number of events 6 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Metabolism and nutrition disorders Hypoalbuminemia	5.8% 8/138 • Number of events 10 • Date treatment consent signed to date off study, approximately 5 years.	2.4% 3/124 • Number of events 3 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	1.3% 2/159 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.
Metabolism and nutrition disorders Hypoglycemia	2.9% 4/138 • Number of events 4 • Date treatment consent signed to date off study, approximately 5 years.	1.6% 2/124 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.
Metabolism and nutrition disorders Hypokalemia	0.72% 1/138 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.
Metabolism and nutrition disorders Hypomagnesmia	1.4% 2/138 • Number of events 3 • Date treatment consent signed to date off study, approximately 5 years.	0.81% 1/124 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	1.9% 3/159 • Number of events 4 • Date treatment consent signed to date off study, approximately 5 years.
Metabolism and nutrition disorders Hyponatremia	2.2% 3/138 • Number of events 3 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	1.3% 2/159 • Number of events 3 • Date treatment consent signed to date off study, approximately 5 years.
Metabolism and nutrition disorders Hypophosphatemia	0.72% 1/138 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.	0.81% 1/124 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.72% 1/138 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Renal and urinary disorders Incontinence	0.72% 1/138 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.81% 1/124 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	1.9% 3/159 • Number of events 3 • Date treatment consent signed to date off study, approximately 5 years.
Infections and infestations Infection without neutropenia	6.5% 9/138 • Number of events 10 • Date treatment consent signed to date off study, approximately 5 years.	5.6% 7/124 • Number of events 11 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	1.9% 3/159 • Number of events 3 • Date treatment consent signed to date off study, approximately 5 years.
Infections and infestations Infection, Other	0.72% 1/138 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	4.8% 6/124 • Number of events 7 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Ear and labyrinth disorders Inner ear/hearing	2.2% 3/138 • Number of events 3 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Musculoskeletal and connective tissue disorders Joint, muscle, or bone (osseous)-Other	2.9% 4/138 • Number of events 4 • Date treatment consent signed to date off study, approximately 5 years.	5.6% 7/124 • Number of events 11 • Date treatment consent signed to date off study, approximately 5 years.	1.3% 2/159 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.	1.9% 3/159 • Number of events 3 • Date treatment consent signed to date off study, approximately 5 years.
Investigations Leukocytes (total WBC)	1.4% 2/138 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.	0.81% 1/124 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.
Ear and labyrinth disorders Middle ear/hearing	0.72% 1/138 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Psychiatric disorders Mood alteration-anxiety agitation	0.72% 1/138 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	1.6% 2/124 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Gastrointestinal disorders Mouth dryness	0.72% 1/138 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Musculoskeletal and connective tissue disorders Myalgia (muscle ache)	1.4% 2/138 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.	0.81% 1/124 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	1.3% 2/159 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.
Musculoskeletal and connective tissue disorders Myositis (inflammation/damage of muscle)	1.4% 2/138 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.
Respiratory, thoracic and mediastinal disorders Nasal congestion	0.72% 1/138 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Nervous system disorders Neuropathic pain (e.g., jaw pain, neurologic pain, phantom limb pain, post-infectious neuralgia, or	0.72% 1/138 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Nervous system disorders Neuropathy-sensory	0.72% 1/138 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.
Investigations Neutrophils/granulocytes (ANC/AGC)	0.72% 1/138 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Ear and labyrinth disorders Ocular-Other	0.72% 1/138 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	1.6% 2/124 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.
Nervous system disorders Pain-Other	2.2% 3/138 • Number of events 3 • Date treatment consent signed to date off study, approximately 5 years.	8.1% 10/124 • Number of events 12 • Date treatment consent signed to date off study, approximately 5 years.	1.3% 2/159 • Number of events 3 • Date treatment consent signed to date off study, approximately 5 years.	1.9% 3/159 • Number of events 3 • Date treatment consent signed to date off study, approximately 5 years.
Skin and subcutaneous tissue disorders Photosensitivity	0.72% 1/138 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.81% 1/124 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Blood and lymphatic system disorders Platelets	0.72% 1/138 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.81% 1/124 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Respiratory, thoracic and mediastinal disorders Pneumonitis/pulmonary infiltrates	0.72% 1/138 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Skin and subcutaneous tissue disorders Pruritus	0.72% 1/138 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.81% 1/124 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Skin and subcutaneous tissue disorders Pulmonary-Other	0.72% 1/138 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Skin and subcutaneous tissue disorders Rash/desquamation	5.1% 7/138 • Number of events 7 • Date treatment consent signed to date off study, approximately 5 years.	1.6% 2/124 • Number of events 4 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.
Renal and urinary disorders Renal/GU-Other	0.72% 1/138 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	2.4% 3/124 • Number of events 5 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Investigations SGPT (ALT)	0.72% 1/138 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	1.9% 3/159 • Number of events 3 • Date treatment consent signed to date off study, approximately 5 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Secondary Malignancy-Other	1.4% 2/138 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.	0.81% 1/124 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	1.9% 3/159 • Number of events 3 • Date treatment consent signed to date off study, approximately 5 years.
Cardiac disorders Sinus bradycardia	1.4% 2/138 • Number of events 3 • Date treatment consent signed to date off study, approximately 5 years.	2.4% 3/124 • Number of events 3 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	1.3% 2/159 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.
Skin and subcutaneous tissue disorders Skin-Other	2.2% 3/138 • Number of events 4 • Date treatment consent signed to date off study, approximately 5 years.	2.4% 3/124 • Number of events 5 • Date treatment consent signed to date off study, approximately 5 years.	1.3% 2/159 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.
Gastrointestinal disorders Stomatitis/pharyngitis (oral/pharyngeal mucositis)	0.72% 1/138 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Injury, poisoning and procedural complications Trauma R. big toe	0.72% 1/138 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Renal and urinary disorders Ureteral obstruction	0.72% 1/138 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Renal and urinary disorders Urinary frequency/urgency	1.4% 2/138 • Number of events 3 • Date treatment consent signed to date off study, approximately 5 years.	3.2% 4/124 • Number of events 4 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Respiratory, thoracic and mediastinal disorders Voice changes/stridor/larynx (e.g., hoarsneness, loss of voice, laryngitis)	0.72% 1/138 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Injury, poisoning and procedural complications Wound	0.72% 1/138 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Musculoskeletal and connective tissue disorders Arthralgia (joint pain)	0.00% 0/138 • Date treatment consent signed to date off study, approximately 5 years.	4.8% 6/124 • Number of events 6 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Musculoskeletal and connective tissue disorders Arthritis	0.00% 0/138 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.
Investigations CPK (creatine phosphokinase)	0.00% 0/138 • Date treatment consent signed to date off study, approximately 5 years.	0.81% 1/124 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.
Gastrointestinal disorders Constipation	0.00% 0/138 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	1.3% 2/159 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.
Gastrointestinal disorders Diarrhea (without colostomy)	0.00% 0/138 • Date treatment consent signed to date off study, approximately 5 years.	2.4% 3/124 • Number of events 3 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.
General disorders Edema	0.00% 0/138 • Date treatment consent signed to date off study, approximately 5 years.	1.6% 2/124 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	1.3% 2/159 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.
Reproductive system and breast disorders Erectile impotence	0.00% 0/138 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.
Blood and lymphatic system disorders Hematologic-Other	0.00% 0/138 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.
Hepatobiliary disorders Hepatic-Other	0.00% 0/138 • Date treatment consent signed to date off study, approximately 5 years.	0.81% 1/124 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.
Vascular disorders Hot flashes/flashes	0.00% 0/138 • Date treatment consent signed to date off study, approximately 5 years.	0.81% 1/124 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	1.3% 2/159 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.
Metabolism and nutrition disorders Hypocalcemia	0.00% 0/138 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.
Vascular disorders Hypotension	0.00% 0/138 • Date treatment consent signed to date off study, approximately 5 years.	0.81% 1/124 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.
Infections and infestations Infection with unknown ANC	0.00% 0/138 • Date treatment consent signed to date off study, approximately 5 years.	0.81% 1/124 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	1.3% 2/159 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.
Psychiatric disorders Insomnia	0.00% 0/138 • Date treatment consent signed to date off study, approximately 5 years.	2.4% 3/124 • Number of events 3 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.
Psychiatric disorders Mood alteration-depression	0.00% 0/138 • Date treatment consent signed to date off study, approximately 5 years.	1.6% 2/124 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/138 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.
Gastrointestinal disorders Proctitis	0.00% 0/138 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.
Gastrointestinal disorders Rectal bleeding/hematochezia	0.00% 0/138 • Date treatment consent signed to date off study, approximately 5 years.	4.8% 6/124 • Number of events 6 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	1.3% 2/159 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.
Investigations SGOT (AST)	0.00% 0/138 • Date treatment consent signed to date off study, approximately 5 years.	1.6% 2/124 • Number of events 3 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.
Cardiac disorders Supraventricular arrhythmias (SVT/atrial fibrillation/flutter)	0.00% 0/138 • Date treatment consent signed to date off study, approximately 5 years.	0.81% 1/124 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.
Nervous system disorders Syncope	1.4% 2/138 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.
Gastrointestinal disorders Taste disturbance (dysgeusia)	0.00% 0/138 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.
Gastrointestinal disorders Vomiting	0.00% 0/138 • Date treatment consent signed to date off study, approximately 5 years.	0.81% 1/124 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.
Investigations Weight loss	0.00% 0/138 • Date treatment consent signed to date off study, approximately 5 years.	0.81% 1/124 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.
Skin and subcutaneous tissue disorders Sweating (diaphoresis)	0.00% 0/138 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Gastrointestinal disorders Nausea	0.00% 0/138 • Date treatment consent signed to date off study, approximately 5 years.	1.6% 2/124 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	1.3% 2/159 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.
Musculoskeletal and connective tissue disorders Muscle weakness (not due to neuropathy)	0.00% 0/138 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Gastrointestinal disorders Gastritis	0.00% 0/138 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Gastrointestinal disorders GI-Other	0.00% 0/138 • Date treatment consent signed to date off study, approximately 5 years.	0.81% 1/124 • Number of events 3 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.
Immune system disorders Allergy-Other	0.00% 0/138 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/124 • Date treatment consent signed to date off study, approximately 5 years.	0.63% 1/159 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Investigations Hemoglobinuria	0.00% 0/138 • Date treatment consent signed to date off study, approximately 5 years.	0.81% 1/124 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Renal and urinary disorders Urinary retention	0.00% 0/138 • Date treatment consent signed to date off study, approximately 5 years.	0.81% 1/124 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Nervous system disorders Vasovagal episode	0.00% 0/138 • Date treatment consent signed to date off study, approximately 5 years.	0.81% 1/124 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Eye disorders Vision-blurred vision	0.00% 0/138 • Date treatment consent signed to date off study, approximately 5 years.	0.81% 1/124 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Nervous system disorders Pyramidal tract dysfunction (e.g., increased tone, hyperreflexia, positive Babinski, decreased fine	0.00% 0/138 • Date treatment consent signed to date off study, approximately 5 years.	0.81% 1/124 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
General disorders Rigors/chills	0.00% 0/138 • Date treatment consent signed to date off study, approximately 5 years.	1.6% 2/124 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Investigations Lymphopenia	0.00% 0/138 • Date treatment consent signed to date off study, approximately 5 years.	0.81% 1/124 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Infections and infestations Laryngitis	0.00% 0/138 • Date treatment consent signed to date off study, approximately 5 years.	0.81% 1/124 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Gastrointestinal disorders Anorexia	0.00% 0/138 • Date treatment consent signed to date off study, approximately 5 years.	1.6% 2/124 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Cardiac disorders Arrhythmia-Other	0.00% 0/138 • Date treatment consent signed to date off study, approximately 5 years.	1.6% 2/124 • Number of events 3 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Nervous system disorders Ataxia (incoordination)	0.00% 0/138 • Date treatment consent signed to date off study, approximately 5 years.	0.81% 1/124 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Investigations Bilirubin	0.00% 0/138 • Date treatment consent signed to date off study, approximately 5 years.	0.81% 1/124 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Cardiac disorders Chest pain (non-cardiac and non-pleuritic)	0.00% 0/138 • Date treatment consent signed to date off study, approximately 5 years.	0.81% 1/124 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
General disorders Constitutional symptoms-Other	0.00% 0/138 • Date treatment consent signed to date off study, approximately 5 years.	1.6% 2/124 • Number of events 4 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
General disorders Fever (in absence of neutropenia where neutropenia is defined as AGC<1.0x109)L	0.00% 0/138 • Date treatment consent signed to date off study, approximately 5 years.	0.81% 1/124 • Number of events 1 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Renal and urinary disorders Dysuria (painful urination)	0.00% 0/138 • Date treatment consent signed to date off study, approximately 5 years.	0.81% 1/124 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.
Nervous system disorders Extrapyramidal/involuntary movement/restlessness	0.00% 0/138 • Date treatment consent signed to date off study, approximately 5 years.	1.6% 2/124 • Number of events 2 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.	0.00% 0/159 • Date treatment consent signed to date off study, approximately 5 years.

Additional Information

William L. Dahut, M.D.

National Cancer Institute, National Institutes of Health

Phone: 301-435-8183

Email: dahutw@mail.nih.gov

Results disclosure agreements

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