Trial Outcomes & Findings for Phase III Randomized Trial of Thalidomide/Dexamethasone Versus Vincristine+Adriamycin+Dexamethasone (VAD) (NCT NCT00215943)

Last Updated: 2014-04-17

Results Overview

Blade (15) criteria for remission in multiple myeloma was used to assess response. Complete Response (CR)includes: Disappearance of the original monoclonal protein from the blood and urine on at least two determinations for a minimum of 6 weeks by immunofixation studies. Partial Response (PR) includes: At least a 50% reduction in the level of serum monoclonal protein for at least two determinations 6 weeks apart. Minimal Response (MR)includes: At least a 25% to 49% reduction in the level of serum monoclonal protein for at least 2 determinations 2 weeks apart.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

90 participants

Primary outcome timeframe

End of Cycle 4 - 4 Months per Participant

Results posted on

2014-04-17

Participant Flow

Recruitment began at Moffitt Cancer Center in June of 2003 and ended prematurely in December of 2007.

90 participants were consented. 83 were eligible and randomized to treatment arms. 2 became ineligible after randomization and prior to treatment. 8 withdrew prior to treatment. 73 began treatment.

Participant milestones

Participant milestones
Measure	Active Comparator: VAD Treatment VAD (vincristine, adriamycin, dexamethasone). Vincristine and adriamycin was administered by continuous infusion via a venous catheter for 96 hours every 28 days. Each 28 days is considered one "cycle" of therapy. Patients were to receive 4 to 6 cycles of therapy. Dexamethasone was taken in pill form. During the first 2 cycles it was taken on days 1-4, 9-12, 17-20. For all other cycles dexamethasone was taken only on days 1-4. Patients were randomized to receive zoledronic acid IV on either Day 1 or 15 of each cycle.	Active Comparator: Thalidomide and Dexamethasone Treatment Thalidomide was taken orally once every day in the evening for four to six months. The dexamethasone was taken in a pill form. During the first 2 cycles it was taken on days 1-4, 9-12, 17-20. For all other cycles dexamethasone was taken only on days 1-4.
Overall Study STARTED	36	37
Overall Study COMPLETED	27	23
Overall Study NOT COMPLETED	9	14

Reasons for withdrawal

Reasons for withdrawal
Measure	Active Comparator: VAD Treatment VAD (vincristine, adriamycin, dexamethasone). Vincristine and adriamycin was administered by continuous infusion via a venous catheter for 96 hours every 28 days. Each 28 days is considered one "cycle" of therapy. Patients were to receive 4 to 6 cycles of therapy. Dexamethasone was taken in pill form. During the first 2 cycles it was taken on days 1-4, 9-12, 17-20. For all other cycles dexamethasone was taken only on days 1-4. Patients were randomized to receive zoledronic acid IV on either Day 1 or 15 of each cycle.	Active Comparator: Thalidomide and Dexamethasone Treatment Thalidomide was taken orally once every day in the evening for four to six months. The dexamethasone was taken in a pill form. During the first 2 cycles it was taken on days 1-4, 9-12, 17-20. For all other cycles dexamethasone was taken only on days 1-4.
Overall Study Disease Progression	3	5
Overall Study Alternate therapy	0	1
Overall Study Adverse Event	3	6
Overall Study Other disease	0	1
Overall Study Other complications	3	1

Baseline Characteristics

Phase III Randomized Trial of Thalidomide/Dexamethasone Versus Vincristine+Adriamycin+Dexamethasone (VAD)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Active Comparator: VAD Treatment n=36 Participants VAD (vincristine, adriamycin, dexamethasone). Vincristine and adriamycin was administered by continuous infusion via a venous catheter for 96 hours every 28 days. Each 28 days is considered one "cycle" of therapy. Patients were to receive 4 to 6 cycles of therapy. Dexamethasone was taken in pill form. During the first 2 cycles it was taken on days 1-4, 9-12, 17-20. For all other cycles dexamethasone was taken only on days 1-4. Patients were randomized to receive zoledronic acid IV on either Day 1 or 15 of each cycle.	Active Comparator: Thalidomide and Dexamethasone Treatment n=37 Participants Thalidomide was taken orally once every day in the evening for four to six months. The dexamethasone was taken in a pill form. During the first 2 cycles it was taken on days 1-4, 9-12, 17-20. For all other cycles dexamethasone was taken only on days 1-4.	Total n=73 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	25 Participants n=5 Participants	27 Participants n=7 Participants	52 Participants n=5 Participants
Age, Categorical >=65 years	11 Participants n=5 Participants	10 Participants n=7 Participants	21 Participants n=5 Participants
Sex: Female, Male Female	15 Participants n=5 Participants	14 Participants n=7 Participants	29 Participants n=5 Participants
Sex: Female, Male Male	21 Participants n=5 Participants	23 Participants n=7 Participants	44 Participants n=5 Participants
Region of Enrollment United States	36 participants n=5 Participants	37 participants n=7 Participants	73 participants n=5 Participants

PRIMARY outcome

Timeframe: End of Cycle 4 - 4 Months per Participant

Population: All evaluable participants

Outcome measures

Outcome measures
Measure	Active Comparator: VAD Treatment n=36 Participants VAD (vincristine, adriamycin, dexamethasone). Vincristine and adriamycin was administered by continuous infusion via a venous catheter for 96 hours every 28 days. Each 28 days is considered one "cycle" of therapy. Patients were to receive 4 to 6 cycles of therapy. Dexamethasone was taken in pill form. During the first 2 cycles it was taken on days 1-4, 9-12, 17-20. For all other cycles dexamethasone was taken only on days 1-4. Patients were randomized to receive zoledronic acid IV on either Day 1 or 15 of each cycle.	Active Comparator: Thalidomide and Dexamethasone Treatment n=37 Participants Thalidomide was taken orally once every day in the evening for four to six months. The dexamethasone was taken in a pill form. During the first 2 cycles it was taken on days 1-4, 9-12, 17-20. For all other cycles dexamethasone was taken only on days 1-4.
Response Rates of VAD vs. Thalidomide/Dexamethasone Complete Response	1 participants	1 participants
Response Rates of VAD vs. Thalidomide/Dexamethasone Partial Response	9 participants	16 participants
Response Rates of VAD vs. Thalidomide/Dexamethasone Minimal Response	6 participants	2 participants

SECONDARY outcome

Timeframe: 4 Years, 7 Months

Population: All evaluable participants

Number of participants with toxicities of Thalidomide/Dexamethasone vs. VAD as induction regimens in newly diagnosed multiple myeloma (MM).

Outcome measures

Outcome measures
Measure	Active Comparator: VAD Treatment n=36 Participants VAD (vincristine, adriamycin, dexamethasone). Vincristine and adriamycin was administered by continuous infusion via a venous catheter for 96 hours every 28 days. Each 28 days is considered one "cycle" of therapy. Patients were to receive 4 to 6 cycles of therapy. Dexamethasone was taken in pill form. During the first 2 cycles it was taken on days 1-4, 9-12, 17-20. For all other cycles dexamethasone was taken only on days 1-4. Patients were randomized to receive zoledronic acid IV on either Day 1 or 15 of each cycle.	Active Comparator: Thalidomide and Dexamethasone Treatment n=37 Participants Thalidomide was taken orally once every day in the evening for four to six months. The dexamethasone was taken in a pill form. During the first 2 cycles it was taken on days 1-4, 9-12, 17-20. For all other cycles dexamethasone was taken only on days 1-4.
Number of Participants With Adverse Events, by Group Serious Adverse Events (SAEs)	0 participants	1 participants
Number of Participants With Adverse Events, by Group Adverse Events (AEs)	36 participants	37 participants

SECONDARY outcome

Timeframe: 4 Months

Population: All evaluable participants

Number of participants with PFS for thalidomide/Dexamethasone vs. VAD with respect to progression free survival in newly diagnosed MM. Progressive Disease (PD): (for patients not in CR) Requires one or more of the following; \> 25% increase in the level of serum monoclonal paraprotein, which must also be an absolute increase of at least 5 g/L and confirmed on a repeat investigation. \> 25% increase in 24-hour urinary light chain excretion, which must also be an absolute increase of at least 200mg and confirmed on a repeat investigation. \>25% increase in plasma cells in a bone marrow aspirate, which also must be an absolute increase of at least 10%. Definite increase in the size of existing lytic lesions or plasmacytomas. Development of new bone lesions or plasmacytomas (except compression fractures). Development of hypercalcemia (corrected calcium \> 11.5 mg/dL not attributable to other causes).

Outcome measures

Outcome measures
Measure	Active Comparator: VAD Treatment n=36 Participants VAD (vincristine, adriamycin, dexamethasone). Vincristine and adriamycin was administered by continuous infusion via a venous catheter for 96 hours every 28 days. Each 28 days is considered one "cycle" of therapy. Patients were to receive 4 to 6 cycles of therapy. Dexamethasone was taken in pill form. During the first 2 cycles it was taken on days 1-4, 9-12, 17-20. For all other cycles dexamethasone was taken only on days 1-4. Patients were randomized to receive zoledronic acid IV on either Day 1 or 15 of each cycle.	Active Comparator: Thalidomide and Dexamethasone Treatment n=37 Participants Thalidomide was taken orally once every day in the evening for four to six months. The dexamethasone was taken in a pill form. During the first 2 cycles it was taken on days 1-4, 9-12, 17-20. For all other cycles dexamethasone was taken only on days 1-4.
Number of Participants With Progression Free Survival (PFS), by Treatment Arm	2 participants	1 participants

SECONDARY outcome

Timeframe: Up to 10 Years

Population: All participants with evaluable follow-up data.

Median OS for thalidomide/Dexamethasone participants vs. VAD participants. Months from On Study to Expired/Last Date Known Alive. Investigators had planned to accrue 176 participants to calculate median overall survival.

Outcome measures

Outcome measures
Measure	Active Comparator: VAD Treatment n=26 Participants VAD (vincristine, adriamycin, dexamethasone). Vincristine and adriamycin was administered by continuous infusion via a venous catheter for 96 hours every 28 days. Each 28 days is considered one "cycle" of therapy. Patients were to receive 4 to 6 cycles of therapy. Dexamethasone was taken in pill form. During the first 2 cycles it was taken on days 1-4, 9-12, 17-20. For all other cycles dexamethasone was taken only on days 1-4. Patients were randomized to receive zoledronic acid IV on either Day 1 or 15 of each cycle.	Active Comparator: Thalidomide and Dexamethasone Treatment n=20 Participants Thalidomide was taken orally once every day in the evening for four to six months. The dexamethasone was taken in a pill form. During the first 2 cycles it was taken on days 1-4, 9-12, 17-20. For all other cycles dexamethasone was taken only on days 1-4.
Overall Survival (OS), by Treatment Arm	57 months Interval 0.0 to 114.0	56.5 months Interval 2.0 to 115.0

Adverse Events

Active Comparator: VAD Treatment

Serious events: 0 serious events

Other events: 36 other events

Deaths: 0 deaths

Active Comparator: Thalidomide and Dexamethasone Treatment

Serious events: 1 serious events

Other events: 37 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Active Comparator: VAD Treatment n=36 participants at risk VAD (vincristine, adriamycin, dexamethasone). Vincristine and adriamycin was administered by continuous infusion via a venous catheter for 96 hours every 28 days. Each 28 days is considered one "cycle" of therapy. Patients were to receive 4 to 6 cycles of therapy. Dexamethasone was taken in pill form. During the first 2 cycles it was taken on days 1-4, 9-12, 17-20. For all other cycles dexamethasone was taken only on days 1-4. Patients were randomized to receive zoledronic acid IV on either Day 1 or 15 of each cycle.	Active Comparator: Thalidomide and Dexamethasone Treatment n=37 participants at risk Thalidomide was taken orally once every day in the evening for four to six months. The dexamethasone was taken in a pill form. During the first 2 cycles it was taken on days 1-4, 9-12, 17-20. For all other cycles dexamethasone was taken only on days 1-4.
Respiratory, thoracic and mediastinal disorders Pneumonitis/pulmonary infiltrates - Grade 4	0.00% 0/36 • 5 years All participants who received treatment	2.7% 1/37 • Number of events 1 • 5 years All participants who received treatment
Respiratory, thoracic and mediastinal disorders Pulmonary/Upper Respiratory - Other - Grade 3	0.00% 0/36 • 5 years All participants who received treatment	2.7% 1/37 • Number of events 1 • 5 years All participants who received treatment

Other adverse events

Additional Information

Melissa Alsina, M.D.

H. Lee Moffitt Cancer Center and Research Institute

Phone: 813-745-6886

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Active Comparator: VAD Treatment n=36 participants at risk VAD (vincristine, adriamycin, dexamethasone). Vincristine and adriamycin was administered by continuous infusion via a venous catheter for 96 hours every 28 days. Each 28 days is considered one "cycle" of therapy. Patients were to receive 4 to 6 cycles of therapy. Dexamethasone was taken in pill form. During the first 2 cycles it was taken on days 1-4, 9-12, 17-20. For all other cycles dexamethasone was taken only on days 1-4. Patients were randomized to receive zoledronic acid IV on either Day 1 or 15 of each cycle.	Active Comparator: Thalidomide and Dexamethasone Treatment n=37 participants at risk Thalidomide was taken orally once every day in the evening for four to six months. The dexamethasone was taken in a pill form. During the first 2 cycles it was taken on days 1-4, 9-12, 17-20. For all other cycles dexamethasone was taken only on days 1-4.
Gastrointestinal disorders Abdominal pain or cramping	2.8% 1/36 • Number of events 1 • 5 years All participants who received treatment	5.4% 2/37 • Number of events 2 • 5 years All participants who received treatment
Metabolism and nutrition disorders Alkaline phosphatase	0.00% 0/36 • 5 years All participants who received treatment	5.4% 2/37 • Number of events 2 • 5 years All participants who received treatment
Skin and subcutaneous tissue disorders Alopecia	47.2% 17/36 • Number of events 18 • 5 years All participants who received treatment	0.00% 0/37 • 5 years All participants who received treatment
Metabolism and nutrition disorders Anorexia	8.3% 3/36 • Number of events 4 • 5 years All participants who received treatment	18.9% 7/37 • Number of events 11 • 5 years All participants who received treatment
Metabolism and nutrition disorders Bilirubin	5.6% 2/36 • Number of events 3 • 5 years All participants who received treatment	0.00% 0/37 • 5 years All participants who received treatment
Musculoskeletal and connective tissue disorders Bone pain	61.1% 22/36 • Number of events 27 • 5 years All participants who received treatment	62.2% 23/37 • Number of events 28 • 5 years All participants who received treatment
Gastrointestinal disorders Colitis	0.00% 0/36 • 5 years All participants who received treatment	5.4% 2/37 • Number of events 2 • 5 years All participants who received treatment
Psychiatric disorders Confusion	0.00% 0/36 • 5 years All participants who received treatment	8.1% 3/37 • Number of events 3 • 5 years All participants who received treatment
Gastrointestinal disorders Constipation	36.1% 13/36 • Number of events 15 • 5 years All participants who received treatment	64.9% 24/37 • Number of events 31 • 5 years All participants who received treatment
Respiratory, thoracic and mediastinal disorders Cough	2.8% 1/36 • Number of events 1 • 5 years All participants who received treatment	13.5% 5/37 • Number of events 5 • 5 years All participants who received treatment
Metabolism and nutrition disorders Creatinine	19.4% 7/36 • Number of events 12 • 5 years All participants who received treatment	16.2% 6/37 • Number of events 14 • 5 years All participants who received treatment
Gastrointestinal disorders Dehydration	13.9% 5/36 • Number of events 7 • 5 years All participants who received treatment	16.2% 6/37 • Number of events 9 • 5 years All participants who received treatment
General disorders Depressed level of consciousness	0.00% 0/36 • 5 years All participants who received treatment	5.4% 2/37 • Number of events 2 • 5 years All participants who received treatment
Gastrointestinal disorders Diarrhea - patients without colostomy	11.1% 4/36 • Number of events 5 • 5 years All participants who received treatment	24.3% 9/37 • Number of events 10 • 5 years All participants who received treatment
General disorders Dizziness/lightheadedness	5.6% 2/36 • Number of events 3 • 5 years All participants who received treatment	16.2% 6/37 • Number of events 7 • 5 years All participants who received treatment
Skin and subcutaneous tissue disorders Dry skin	2.8% 1/36 • Number of events 1 • 5 years All participants who received treatment	5.4% 2/37 • Number of events 2 • 5 years All participants who received treatment
Gastrointestinal disorders Dyspepsia/heartburn	5.6% 2/36 • Number of events 2 • 5 years All participants who received treatment	8.1% 3/37 • Number of events 3 • 5 years All participants who received treatment
Gastrointestinal disorders Dysphagia, esophagitis, odynophagia (painful swallowing)	0.00% 0/36 • 5 years All participants who received treatment	5.4% 2/37 • Number of events 2 • 5 years All participants who received treatment
Respiratory, thoracic and mediastinal disorders Dyspnea (shortness of breath)	22.2% 8/36 • Number of events 9 • 5 years All participants who received treatment	40.5% 15/37 • Number of events 17 • 5 years All participants who received treatment
Renal and urinary disorders Dysuria (painful urination)	0.00% 0/36 • 5 years All participants who received treatment	5.4% 2/37 • Number of events 2 • 5 years All participants who received treatment
Blood and lymphatic system disorders Edema	16.7% 6/36 • Number of events 7 • 5 years All participants who received treatment	32.4% 12/37 • Number of events 15 • 5 years All participants who received treatment
General disorders Fatigue (lethargy, malaise, asthenia)	50.0% 18/36 • Number of events 20 • 5 years All participants who received treatment	45.9% 17/37 • Number of events 21 • 5 years All participants who received treatment
General disorders Fever (in the absence of neutropenia)	8.3% 3/36 • Number of events 3 • 5 years All participants who received treatment	16.2% 6/37 • Number of events 8 • 5 years All participants who received treatment
Renal and urinary disorders Hematuria (in the absence of vaginal bleeding)	0.00% 0/36 • 5 years All participants who received treatment	5.4% 2/37 • Number of events 2 • 5 years All participants who received treatment
Blood and lymphatic system disorders Low Hemoglobin	94.4% 34/36 • Number of events 70 • 5 years All participants who received treatment	83.8% 31/37 • Number of events 81 • 5 years All participants who received treatment
Metabolism and nutrition disorders Hypercalcemia	13.9% 5/36 • Number of events 6 • 5 years All participants who received treatment	10.8% 4/37 • Number of events 8 • 5 years All participants who received treatment
Metabolism and nutrition disorders Hyperglycemia	30.6% 11/36 • Number of events 28 • 5 years All participants who received treatment	32.4% 12/37 • Number of events 23 • 5 years All participants who received treatment
Metabolism and nutrition disorders Hyperkalemia	8.3% 3/36 • Number of events 3 • 5 years All participants who received treatment	10.8% 4/37 • Number of events 6 • 5 years All participants who received treatment
Metabolism and nutrition disorders Hypermagnesemia	5.6% 2/36 • Number of events 2 • 5 years All participants who received treatment	2.7% 1/37 • Number of events 1 • 5 years All participants who received treatment
Cardiac disorders Hypertension	8.3% 3/36 • Number of events 3 • 5 years All participants who received treatment	5.4% 2/37 • Number of events 2 • 5 years All participants who received treatment
Metabolism and nutrition disorders Hyperuricemia	5.6% 2/36 • Number of events 4 • 5 years All participants who received treatment	5.4% 2/37 • Number of events 5 • 5 years All participants who received treatment
Blood and lymphatic system disorders Hypoalbuminemia	19.4% 7/36 • Number of events 8 • 5 years All participants who received treatment	18.9% 7/37 • Number of events 13 • 5 years All participants who received treatment
Metabolism and nutrition disorders Hypocalcemia	27.8% 10/36 • Number of events 17 • 5 years All participants who received treatment	35.1% 13/37 • Number of events 19 • 5 years All participants who received treatment
Metabolism and nutrition disorders Hypokalemia	11.1% 4/36 • Number of events 10 • 5 years All participants who received treatment	13.5% 5/37 • Number of events 7 • 5 years All participants who received treatment
Metabolism and nutrition disorders Hypomagnesemia	11.1% 4/36 • Number of events 6 • 5 years All participants who received treatment	5.4% 2/37 • Number of events 5 • 5 years All participants who received treatment
Metabolism and nutrition disorders Hyponatremia	19.4% 7/36 • Number of events 10 • 5 years All participants who received treatment	13.5% 5/37 • Number of events 5 • 5 years All participants who received treatment
Metabolism and nutrition disorders Hypophosphatemia	27.8% 10/36 • Number of events 15 • 5 years All participants who received treatment	29.7% 11/37 • Number of events 13 • 5 years All participants who received treatment
Cardiac disorders Hypotension	5.6% 2/36 • Number of events 3 • 5 years All participants who received treatment	2.7% 1/37 • Number of events 1 • 5 years All participants who received treatment
Endocrine disorders Hypothyroidism	0.00% 0/36 • 5 years All participants who received treatment	5.4% 2/37 • Number of events 2 • 5 years All participants who received treatment
Respiratory, thoracic and mediastinal disorders Hypoxia	5.6% 2/36 • Number of events 4 • 5 years All participants who received treatment	2.7% 1/37 • Number of events 2 • 5 years All participants who received treatment
Infections and infestations Infection without neutropenia	30.6% 11/36 • Number of events 14 • 5 years All participants who received treatment	27.0% 10/37 • Number of events 17 • 5 years All participants who received treatment
General disorders Insomnia	16.7% 6/36 • Number of events 6 • 5 years All participants who received treatment	16.2% 6/37 • Number of events 6 • 5 years All participants who received treatment
Blood and lymphatic system disorders Low Leukocytes (total WBC)	16.7% 6/36 • Number of events 11 • 5 years All participants who received treatment	18.9% 7/37 • Number of events 14 • 5 years All participants who received treatment
Blood and lymphatic system disorders Lymphopenia	13.9% 5/36 • Number of events 13 • 5 years All participants who received treatment	8.1% 3/37 • Number of events 12 • 5 years All participants who received treatment
Gastrointestinal disorders Melena/GI bleeding	2.8% 1/36 • Number of events 1 • 5 years All participants who received treatment	5.4% 2/37 • Number of events 2 • 5 years All participants who received treatment
General disorders Mood alteration-anxiety, agitation	8.3% 3/36 • Number of events 3 • 5 years All participants who received treatment	8.1% 3/37 • Number of events 3 • 5 years All participants who received treatment
Gastrointestinal disorders Mouth dryness	0.00% 0/36 • 5 years All participants who received treatment	5.4% 2/37 • Number of events 2 • 5 years All participants who received treatment
Musculoskeletal and connective tissue disorders Muscle weakness (not due to neuropathy)	5.6% 2/36 • Number of events 3 • 5 years All participants who received treatment	13.5% 5/37 • Number of events 6 • 5 years All participants who received treatment
Musculoskeletal and connective tissue disorders Myalgia (muscle pain)	0.00% 0/36 • 5 years All participants who received treatment	5.4% 2/37 • Number of events 2 • 5 years All participants who received treatment
Gastrointestinal disorders Nausea	30.6% 11/36 • Number of events 15 • 5 years All participants who received treatment	21.6% 8/37 • Number of events 12 • 5 years All participants who received treatment
Musculoskeletal and connective tissue disorders Neuropathic pain (e.g., jaw pain, neurologic pain, phantom limb pain, post-infectious neuralgia, or	5.6% 2/36 • Number of events 2 • 5 years All participants who received treatment	0.00% 0/37 • 5 years All participants who received treatment
Musculoskeletal and connective tissue disorders Neuropathy - motor	8.3% 3/36 • Number of events 3 • 5 years All participants who received treatment	13.5% 5/37 • Number of events 6 • 5 years All participants who received treatment
Musculoskeletal and connective tissue disorders Neuropathy - sensory	25.0% 9/36 • Number of events 9 • 5 years All participants who received treatment	37.8% 14/37 • Number of events 15 • 5 years All participants who received treatment
Blood and lymphatic system disorders Low Neutrophils/granulocytes (ANC/AGC)	13.9% 5/36 • Number of events 9 • 5 years All participants who received treatment	16.2% 6/37 • Number of events 15 • 5 years All participants who received treatment
Blood and lymphatic system disorders Low Platelets	25.0% 9/36 • Number of events 20 • 5 years All participants who received treatment	27.0% 10/37 • Number of events 23 • 5 years All participants who received treatment
Respiratory, thoracic and mediastinal disorders Pleural effusion (non-malignant)	0.00% 0/36 • 5 years All participants who received treatment	8.1% 3/37 • Number of events 3 • 5 years All participants who received treatment
Respiratory, thoracic and mediastinal disorders Pneumonitis/pulmonary infiltrates	0.00% 0/36 • 5 years All participants who received treatment	16.2% 6/37 • Number of events 8 • 5 years All participants who received treatment
Blood and lymphatic system disorders Prothrombin time (PT)	0.00% 0/36 • 5 years All participants who received treatment	10.8% 4/37 • Number of events 11 • 5 years All participants who received treatment
Skin and subcutaneous tissue disorders Rash/desquamation	5.6% 2/36 • Number of events 2 • 5 years All participants who received treatment	18.9% 7/37 • Number of events 8 • 5 years All participants who received treatment
Renal and urinary disorders Renal failure	5.6% 2/36 • Number of events 2 • 5 years All participants who received treatment	0.00% 0/37 • 5 years All participants who received treatment
General disorders Rigors, chills	5.6% 2/36 • Number of events 2 • 5 years All participants who received treatment	5.4% 2/37 • Number of events 2 • 5 years All participants who received treatment
Metabolism and nutrition disorders SGOT (AST) (serum glutamic oxaloacetic transaminase)	2.8% 1/36 • Number of events 1 • 5 years All participants who received treatment	5.4% 2/37 • Number of events 5 • 5 years All participants who received treatment
Metabolism and nutrition disorders SGPT (ALT) (serum glutamic pyruvic transaminase)	5.6% 2/36 • Number of events 2 • 5 years All participants who received treatment	8.1% 3/37 • Number of events 6 • 5 years All participants who received treatment
Cardiac disorders Sinus bradycardia	0.00% 0/36 • 5 years All participants who received treatment	5.4% 2/37 • Number of events 2 • 5 years All participants who received treatment
Gastrointestinal disorders Stomatitis/pharyngitis (oral/pharyngeal mucositis)	33.3% 12/36 • Number of events 12 • 5 years All participants who received treatment	8.1% 3/37 • Number of events 3 • 5 years All participants who received treatment
Cardiac disorders Supraventricular arrhythmias (SVT/atrial fibrillation/flutter)	0.00% 0/36 • 5 years All participants who received treatment	5.4% 2/37 • Number of events 2 • 5 years All participants who received treatment
General disorders Sweating (diaphoresis)	5.6% 2/36 • Number of events 2 • 5 years All participants who received treatment	8.1% 3/37 • Number of events 3 • 5 years All participants who received treatment
General disorders Syncope (fainting)	0.00% 0/36 • 5 years All participants who received treatment	8.1% 3/37 • Number of events 3 • 5 years All participants who received treatment
Gastrointestinal disorders Taste disturbance (dysgeusia)	8.3% 3/36 • Number of events 4 • 5 years All participants who received treatment	10.8% 4/37 • Number of events 4 • 5 years All participants who received treatment
Vascular disorders Thrombosis/embolism	19.4% 7/36 • Number of events 7 • 5 years All participants who received treatment	18.9% 7/37 • Number of events 7 • 5 years All participants who received treatment
Blood and lymphatic system disorders Transfusion - Platelets	5.6% 2/36 • Number of events 2 • 5 years All participants who received treatment	5.4% 2/37 • Number of events 4 • 5 years All participants who received treatment
Blood and lymphatic system disorders Transfusion: pRBCs	16.7% 6/36 • Number of events 7 • 5 years All participants who received treatment	10.8% 4/37 • Number of events 8 • 5 years All participants who received treatment
General disorders Tremor	0.00% 0/36 • 5 years All participants who received treatment	18.9% 7/37 • Number of events 9 • 5 years All participants who received treatment
Gastrointestinal disorders Vomiting	5.6% 2/36 • Number of events 3 • 5 years All participants who received treatment	10.8% 4/37 • Number of events 5 • 5 years All participants who received treatment
General disorders Weight loss	8.3% 3/36 • Number of events 3 • 5 years All participants who received treatment	10.8% 4/37 • Number of events 5 • 5 years All participants who received treatment