Trial Outcomes & Findings for Bevacizumab and Erlotinib After Radiation Therapy and Temozolomide in Treating Patients With Newly Diagnosed Glioblastoma Multiforme or Gliosarcoma (NCT NCT00720356)

NCT ID: NCT00720356

Last Updated: 2018-10-26

Results Overview

Overall survival (OS) will be measured from the start of treatment until death from any cause. At data cut off patients remaining alive will be censored at the last known date of contact.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

115 participants

Primary outcome timeframe

From start of treatment, during treatment and every 3 months following the end of treatment until death. Median follow up at time of OS data was 33 months.

Results posted on

2018-10-26

Participant Flow

The study was ready for accrual March 12, 2009 with an accrual goal of up to 50 patients. The first patient was enrolled on July 7 2009. Accrual was suspended on July 29 2010 and reopened on March 30, 2011. The study was closed permanently on November 03, 2011 with an accrual of 48 patients treated on study after screening 115 patients.

Registration is a two step process. ICF signed, tissue sent off and MGMT promoter methylation status determined eligibility. Patients with unmethylated MGMT promoters will be complete the second registration step and be treated on study. Patients with methylated MGMT promoters will not be treated on study.

Participant milestones

Participant milestones
Measure	Erlotinib and Bevacizumab Combination Treatment Erlotinib and bevacizumab Bevacizumab: 10mg/kg administered intravenously every 2 weeks Erlotinib hydrochloride: 150 mg/daily orally
Registration to Study STARTED	115
Registration to Study Completed Registration Step 1	115
Registration to Study Completed Registration Step 2	48
Registration to Study COMPLETED	48
Registration to Study NOT COMPLETED	67
Reached 1st Response/2 Cycles STARTED	48
Reached 1st Response/2 Cycles COMPLETED	46
Reached 1st Response/2 Cycles NOT COMPLETED	2
Went on to be Treated Cycle 3 STARTED	46
Went on to be Treated Cycle 3 COMPLETED	44
Went on to be Treated Cycle 3 NOT COMPLETED	2
Follow up Until Death STARTED	48
Follow up Until Death COMPLETED	43
Follow up Until Death NOT COMPLETED	5

Reasons for withdrawal

Reasons for withdrawal
Measure	Erlotinib and Bevacizumab Combination Treatment Erlotinib and bevacizumab Bevacizumab: 10mg/kg administered intravenously every 2 weeks Erlotinib hydrochloride: 150 mg/daily orally
Registration to Study Determined to have methylated MGMT	67
Reached 1st Response/2 Cycles Progressive Disease	1
Reached 1st Response/2 Cycles Withdrawal by Subject	1
Went on to be Treated Cycle 3 Adverse Event	1
Went on to be Treated Cycle 3 Physician Decision	1
Follow up Until Death Withdrawal by Subject	1
Follow up Until Death Alive at last data collection	4

Baseline Characteristics

Bevacizumab and Erlotinib After Radiation Therapy and Temozolomide in Treating Patients With Newly Diagnosed Glioblastoma Multiforme or Gliosarcoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment n=115 Participants Erlotinib and bevacizumab Bevacizumab: 10mg/kg administered intravenously every 2 weeks Erlotinib hydrochloride: 150 mg/daily orally
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	82 Participants n=5 Participants
Age, Categorical >=65 years	33 Participants n=5 Participants
Sex: Female, Male Female	45 Participants n=5 Participants
Sex: Female, Male Male	70 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants
Race (NIH/OMB) White	109 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants
Region of Enrollment United States	115 participants n=5 Participants
Methylated/unmethylated MGMT promoter Methylated MGMT promoter	67 Participants n=5 Participants
Methylated/unmethylated MGMT promoter Unmethylated MGMT promoter	48 Participants n=5 Participants

PRIMARY outcome

Timeframe: From start of treatment, during treatment and every 3 months following the end of treatment until death. Median follow up at time of OS data was 33 months.

Population: 2 patients were not evaluable - 1 patient withdrew consent and 1 patient completed less than 1 cycle of treatment

Overall survival (OS) will be measured from the start of treatment until death from any cause. At data cut off patients remaining alive will be censored at the last known date of contact.

Outcome measures

Outcome measures
Measure	Erlotinib and Bevacizumab Combination Treatment n=46 Participants Erlotinib and bevacizumab Bevacizumab: 10mg/kg administered intravenously every 2 weeks Erlotinib hydrochloride: 150 mg/daily orally
Overall Survival	13.2 Months Interval 10.8 to 19.6

SECONDARY outcome

Timeframe: At 12 months from start of treatment

Population: Two patients were determined not to be evaluable (one patient withdrew consent from the study and one patient completed one cycle)

Progression free survival (PFS) will be assessed by CT or MRI scan using McDonald criteria. Progressive disease (PD) is defined as 25% increase in the sum of products of all measurable lesions over smallest sum observed (over baseline if no decrease) using the same techniques as baseline, OR clear worsening of any evaluable disease, OR appearance of any new lesion/site, OR failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer). Stable or increased dose of steroids. PFS will be measured from the start of treatment until first documentation of PD or death.

Outcome measures

Outcome measures
Measure	Erlotinib and Bevacizumab Combination Treatment n=46 Participants Erlotinib and bevacizumab Bevacizumab: 10mg/kg administered intravenously every 2 weeks Erlotinib hydrochloride: 150 mg/daily orally
Progression-free Survival at 12 Months	32 percentage of patients

SECONDARY outcome

Timeframe: From the start of treatment, every 2 cycles (1 cycle = 28 days) during treatment until progressive disease

Population: Two patients were determined not to be evaluable (one patient withdrew consent from the study and one patient complete one cycle of treatment only)

Response Rate (RR) will be defined as the best response seen during treatment measured by CT/MRI scan every 8 weeks during treatment using McDonald Criteria. CR=Complete disappearance of all measurable and evaluable disease. No new lesions. No evidence of non-evaluable disease. Patients off steroids. PR=Greater than or equal to 50% decrease under baseline in the sum of products of perpendicular diameters of all measurable lesions. No progression of evaluable disease. No new lesions. Stable/decreased dose of steroids. Stable/No Response=Does not qualify for CR, PR, or progression. The designation of Stable/No Response requires a minimum of 8 weeks duration. Stable/decreased dose of steroids. Progressive disease = 25% increase in the sum of products of all measurable lesions over smallest sum observed (over baseline if no decrease), worsening of evaluable disease, new lesions/site, failure to return for evaluation due to death or deteriorating condition.

Outcome measures

Outcome measures
Measure	Erlotinib and Bevacizumab Combination Treatment n=46 Participants Erlotinib and bevacizumab Bevacizumab: 10mg/kg administered intravenously every 2 weeks Erlotinib hydrochloride: 150 mg/daily orally
Response Rate (RR) Complete Response	4 Participants
Response Rate (RR) Partial Response	12 Participants
Response Rate (RR) Stable/no response	28 Participants
Response Rate (RR) Progressive Disease	0 Participants
Response Rate (RR) No Evaluable Disease (NED)	2 Participants

SECONDARY outcome

Timeframe: From the start of treatment, at the beginning of every cycle (1 cycle = 28 days) during treatment until 30 days after completion of treatment for up to 49 cycles.

Population: All patients that received at least one dose of study drug were evaluable for toxicity. Data for grade 3 and 4 toxicities during treatment were collected.

Toxicity data for combination treatment of erlotinib and bevacizumab will be collected on day 1 of every cycle (1 cycle = 28 days) during treatment according to the National Cancer Institute's Common Toxicity Criteria for adverse events version 3.0 (CTCAE v3.0). In general adverse events (AEs) will be graded according to the following: Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe AE Grade 4 Life-threatening or disabling AE Grade 5 Death related to AE

Outcome measures

Outcome measures
Measure	Erlotinib and Bevacizumab Combination Treatment n=48 Participants Erlotinib and bevacizumab Bevacizumab: 10mg/kg administered intravenously every 2 weeks Erlotinib hydrochloride: 150 mg/daily orally
Safety of the Combination of Erlotinib and Bevacizumab in This Patient Population Pain head/headache	1 patients
Safety of the Combination of Erlotinib and Bevacizumab in This Patient Population Bowel perforation	1 patients
Safety of the Combination of Erlotinib and Bevacizumab in This Patient Population Hypophosphatemia	1 patients
Safety of the Combination of Erlotinib and Bevacizumab in This Patient Population Rash/desqyamation	5 patients
Safety of the Combination of Erlotinib and Bevacizumab in This Patient Population Rash/acneform	2 patients
Safety of the Combination of Erlotinib and Bevacizumab in This Patient Population Syncope	1 patients
Safety of the Combination of Erlotinib and Bevacizumab in This Patient Population Thrombosis/embolism	2 patients
Safety of the Combination of Erlotinib and Bevacizumab in This Patient Population Wound complication	1 patients
Safety of the Combination of Erlotinib and Bevacizumab in This Patient Population Hyberbilirubinemia	1 patients
Safety of the Combination of Erlotinib and Bevacizumab in This Patient Population Cerebrovascular ischemia	1 patients
Safety of the Combination of Erlotinib and Bevacizumab in This Patient Population Dehydration	1 patients
Safety of the Combination of Erlotinib and Bevacizumab in This Patient Population Dermatology/Skin	1 patients
Safety of the Combination of Erlotinib and Bevacizumab in This Patient Population Hypertension	3 patients
Safety of the Combination of Erlotinib and Bevacizumab in This Patient Population Fatigue	3 patients
Safety of the Combination of Erlotinib and Bevacizumab in This Patient Population Leukocytes	1 patients
Safety of the Combination of Erlotinib and Bevacizumab in This Patient Population Lymphopenia	12 patients
Safety of the Combination of Erlotinib and Bevacizumab in This Patient Population Heartburn	1 patients
Safety of the Combination of Erlotinib and Bevacizumab in This Patient Population Pain (not otherwise specified)	1 patients
Safety of the Combination of Erlotinib and Bevacizumab in This Patient Population Pain abdomen	1 patients

SECONDARY outcome

Timeframe: At 18 months from start of treatment

Population: Most patients had progressed before the 18 month time point. Data was not collected for PFS at 18 months.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Prior to study treatment (after surgery, but before radiation), just before study treatment (within 14 days prior to first treatment) and then every 2 cycles during study treatment, where 1 cycle equals 28 days for a maximum of 49 cycles.

Population: This was an optional portion of the study that patients could participate in. Data was not collected or analyzed for this outcome measure.

Data from consenting patients will be used to assess of changes in tumor blood flow based on MR perfusion using MRI scans. Two scans will be completed prior to treatment on study; the first after surgery buta before radiation, the second within 14 days before starting combination treatment or erlotinib and bevacizumab. Then scans will be completed every 2 cycles during treatment, where one cycle equals 28 days.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: At baseline and then plasma only will be collected every odd cycle (1 cycle = 28 days) during treatment for a maximum of 49 cycles.

Population: This was an optional portion of the study for consenting patients. No data was collected and analyzed for this outcome measure.

Tissue and plasma collected from consenting patients in the study will be used to correlate tumor tissue with imaging and outcomes. Tissue will be collected before treatment on study begins and plasma will be collected the first day of treatment (before treatment) and every odd cycle after that, whilst on study treatment. Tissue and plasma analysis will be correlated with patients imaging results and response to to treatment

Outcome measures

Outcome data not reported

POST_HOC outcome

Timeframe: At 6 months from start of treatment

Population: Two patients were not evaluable.

Outcome measures

Outcome measures
Measure	Erlotinib and Bevacizumab Combination Treatment n=46 Participants Erlotinib and bevacizumab Bevacizumab: 10mg/kg administered intravenously every 2 weeks Erlotinib hydrochloride: 150 mg/daily orally
Progression Free Survival at 6 Months	66.3 percentage of patients

POST_HOC outcome

Timeframe: At 12 months from start of treatment

Population: Two patients were not evaluable

Overall Survival (OS) is measured from start of treatment until death from any cause.

Outcome measures

Outcome measures
Measure	Erlotinib and Bevacizumab Combination Treatment n=46 Participants Erlotinib and bevacizumab Bevacizumab: 10mg/kg administered intravenously every 2 weeks Erlotinib hydrochloride: 150 mg/daily orally
Overall Survival at 12 Months	54.5 percentage of patients

POST_HOC outcome

Timeframe: At 24 months from first treatment

Population: Two patients were not evaluable

Overall Survival (OS) will be measured from start of treatment until death of any cause

Outcome measures

Outcome measures
Measure	Erlotinib and Bevacizumab Combination Treatment n=46 Participants Erlotinib and bevacizumab Bevacizumab: 10mg/kg administered intravenously every 2 weeks Erlotinib hydrochloride: 150 mg/daily orally
Overall Survival at 24 Months	32.8 percentage of patients

POST_HOC outcome

Timeframe: From the start of treatment and every 2 cycles, where 1 cycle equals 28 days, during treatment. Median follow up at time of data was 33 months.

Population: Two patients were not evaluable

Outcome measures

Outcome measures
Measure	Erlotinib and Bevacizumab Combination Treatment n=46 Participants Erlotinib and bevacizumab Bevacizumab: 10mg/kg administered intravenously every 2 weeks Erlotinib hydrochloride: 150 mg/daily orally
Median Progression Free Survival	9.2 months Interval 6.4 to 11.3

Adverse Events

Erlotinib and Bevacizumab Combination Treatment

Serious events: 15 serious events

Other events: 48 other events

Deaths: 43 deaths

Serious adverse events

Serious adverse events
Measure	Erlotinib and Bevacizumab Combination Treatment n=48 participants at risk Erlotinib and bevacizumab Bevacizumab: 10mg/kg administered intravenously every 2 weeks Erlotinib hydrochloride: 150 mg/daily orally
Cardiac disorders Hypertension	2.1% 1/48 • Number of events 1 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Gastrointestinal disorders Nausea	2.1% 1/48 • Number of events 1 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Gastrointestinal disorders Vomiting	2.1% 1/48 • Number of events 1 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Gastrointestinal disorders Dehydration	2.1% 1/48 • Number of events 1 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Gastrointestinal disorders Small bowel perforation	2.1% 1/48 • Number of events 1 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Infections and infestations Infection	2.1% 1/48 • Number of events 1 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Injury, poisoning and procedural complications Death	2.1% 1/48 • Number of events 1 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Injury, poisoning and procedural complications International Normalized Ratio of Prothrombin time (INR)	2.1% 1/48 • Number of events 1 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Metabolism and nutrition disorders Creatinine	2.1% 1/48 • Number of events 1 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Metabolism and nutrition disorders Potassium - serum low	2.1% 1/48 • Number of events 1 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Musculoskeletal and connective tissue disorders General Muscle Weakness	2.1% 1/48 • Number of events 1 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Musculoskeletal and connective tissue disorders Back pain	4.2% 2/48 • Number of events 2 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Nervous system disorders CNS cerebrovascular ischemia	2.1% 1/48 • Number of events 1 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Nervous system disorders Confusion	2.1% 1/48 • Number of events 1 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Nervous system disorders Facial droop	2.1% 1/48 • Number of events 1 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Nervous system disorders Neuropathy - Motor	2.1% 1/48 • Number of events 1 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Nervous system disorders Seizure	10.4% 5/48 • Number of events 5 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Nervous system disorders Headache	4.2% 2/48 • Number of events 2 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Respiratory, thoracic and mediastinal disorders Pneumonitis	2.1% 1/48 • Number of events 1 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Skin and subcutaneous tissue disorders Wound complication (non infectious)	2.1% 1/48 • Number of events 1 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Vascular disorders Thrombosis	4.2% 2/48 • Number of events 2 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)

Other adverse events

Other adverse events
Measure	Erlotinib and Bevacizumab Combination Treatment n=48 participants at risk Erlotinib and bevacizumab Bevacizumab: 10mg/kg administered intravenously every 2 weeks Erlotinib hydrochloride: 150 mg/daily orally
Immune system disorders Allergic rhinitis	12.5% 6/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Blood and lymphatic system disorders Hemoglobin (anemia)	20.8% 10/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Blood and lymphatic system disorders Leukocytes (total white blood cells)	22.9% 11/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Blood and lymphatic system disorders Lymphopenia	52.1% 25/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Blood and lymphatic system disorders Platelets (thrombocytopenia)	20.8% 10/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Cardiac disorders Hypertension	25.0% 12/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Cardiac disorders Sinus bradycardia	6.2% 3/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
General disorders Fatigue	60.4% 29/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
General disorders Fever	6.2% 3/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
General disorders Insomnia	8.3% 4/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
General disorders Rigors	10.4% 5/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
General disorders Weight loss	22.9% 11/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Skin and subcutaneous tissue disorders Brusing	10.4% 5/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Skin and subcutaneous tissue disorders Cheilitis	8.3% 4/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Skin and subcutaneous tissue disorders Dry skin	33.3% 16/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Skin and subcutaneous tissue disorders Nail changes	14.6% 7/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Skin and subcutaneous tissue disorders Pruirtus/itching	37.5% 18/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Skin and subcutaneous tissue disorders Rash acne	27.1% 13/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Skin and subcutaneous tissue disorders Rash/desquamation	75.0% 36/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Gastrointestinal disorders Anorexia	29.2% 14/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Gastrointestinal disorders Constipation	22.9% 11/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Gastrointestinal disorders Dehydration	8.3% 4/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Gastrointestinal disorders Diarrhea	81.2% 39/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Gastrointestinal disorders Dry mouth	6.2% 3/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Gastrointestinal disorders Flatulence	8.3% 4/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Gastrointestinal disorders Heartburn	14.6% 7/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Gastrointestinal disorders Hemorrhoids	20.8% 10/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Gastrointestinal disorders Incontinence anal	6.2% 3/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Gastrointestinal disorders Mucositis/stomatitis	10.4% 5/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Gastrointestinal disorders Nausea	50.0% 24/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Gastrointestinal disorders Taste alteration (dysgeusia)	12.5% 6/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Gastrointestinal disorders Vomiting	18.8% 9/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Gastrointestinal disorders Hemmorhage, GI rectum	10.4% 5/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Respiratory, thoracic and mediastinal disorders Nosebleed	22.9% 11/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Skin and subcutaneous tissue disorders Petechiae/purpura	8.3% 4/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Infections and infestations Sinus infection	8.3% 4/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Respiratory, thoracic and mediastinal disorders Upper airway infection	6.2% 3/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Infections and infestations Urinary tract infection	12.5% 6/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Infections and infestations Skin rash	6.2% 3/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Blood and lymphatic system disorders Edema in limbs	14.6% 7/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Metabolism and nutrition disorders Albumin - serum low	39.6% 19/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Metabolism and nutrition disorders Alkaline phosphatase	6.2% 3/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Metabolism and nutrition disorders Serum glutamic pyruvic transaminase (ALT/SGPT)	14.6% 7/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Metabolism and nutrition disorders serum glutamic oxaloacetic transaminase (AST/SGOT)	22.9% 11/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Metabolism and nutrition disorders Bicarbonate - serum low	6.2% 3/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Metabolism and nutrition disorders Bilirubin, serum high	45.8% 22/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Metabolism and nutrition disorders Calcium, serum low	16.7% 8/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Metabolism and nutrition disorders Creatinine, high	12.5% 6/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Metabolism and nutrition disorders Glucose, serum high	39.6% 19/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Metabolism and nutrition disorders Glucose, serum low	16.7% 8/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Metabolism and nutrition disorders Lactic acid dehydrogenase (LDH)	10.4% 5/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Metabolism and nutrition disorders Magnesium, serum low	31.2% 15/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Metabolism and nutrition disorders Phosphate, serum high	6.2% 3/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Metabolism and nutrition disorders Phosphate, serum low	8.3% 4/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Metabolism and nutrition disorders Potassium, serum high	16.7% 8/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Metabolism and nutrition disorders Potassium, serum low	22.9% 11/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Metabolism and nutrition disorders Proteinuria	12.5% 6/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Metabolism and nutrition disorders Sodium, serum high	14.6% 7/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Metabolism and nutrition disorders Decreased Uric acid	6.2% 3/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Metabolism and nutrition disorders Chloride, serum high	8.3% 4/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Metabolism and nutrition disorders Carbon dioxide increased	12.5% 6/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Metabolism and nutrition disorders Protein - decreased	8.3% 4/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Metabolism and nutrition disorders Increased Blood Urea Nitrogen (BUN)	12.5% 6/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Musculoskeletal and connective tissue disorders Extremity lower (gait/walking)	18.8% 9/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Musculoskeletal and connective tissue disorders Joint function	8.3% 4/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Musculoskeletal and connective tissue disorders Muscle weakness, generalized or specific area - lower extremity	12.5% 6/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Musculoskeletal and connective tissue disorders Muscle weakness, generalized or specific area - whole body	14.6% 7/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Nervous system disorders Ataxia (incoordination)	6.2% 3/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cognitive disturbance	8.3% 4/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Nervous system disorders Confusion	8.3% 4/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Nervous system disorders Dizziness	25.0% 12/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Nervous system disorders Memory impairment	25.0% 12/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Psychiatric disorders Mood alteration - Agitation	10.4% 5/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Psychiatric disorders Mood alteration - Anxiety	10.4% 5/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Psychiatric disorders Mood alteration - Depression	18.8% 9/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Nervous system disorders Sensory Neuropathy	10.4% 5/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Nervous system disorders Pyramidal tract dysfunction (increased tone, hyperreflexia, positive Babinski, decreased fine motor)	6.2% 3/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Nervous system disorders Seizure	14.6% 7/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Nervous system disorders Speech impairment (e.g. dysphasia/ aphasia)	10.4% 5/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Nervous system disorders Tremor	10.4% 5/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Eye disorders Dry eye syndrome	12.5% 6/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Eye disorders Vision impairment (hemianopsia/quadrantanopia)	8.3% 4/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Gastrointestinal disorders Abdominal pain	22.9% 11/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Musculoskeletal and connective tissue disorders Back pain	12.5% 6/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Musculoskeletal and connective tissue disorders Extremity- limb pain	16.7% 8/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Musculoskeletal and connective tissue disorders Joint pain	10.4% 5/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Nervous system disorders Headache	47.9% 23/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Respiratory, thoracic and mediastinal disorders Throat pain	6.2% 3/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Respiratory, thoracic and mediastinal disorders Cough	20.8% 10/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Respiratory, thoracic and mediastinal disorders Dyspnea (shortness of breath)	6.2% 3/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Respiratory, thoracic and mediastinal disorders Voice changes/dysarthria ( hoarseness, loss or alteration in voice, laryngitis)	10.4% 5/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Renal and urinary disorders Urinary incontinence	8.3% 4/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)
Vascular disorders Thrombosis/embolism	6.2% 3/48 • Adverse events (AE) were collected over a 9 year period for the study. AEs were assessed and recorded at the beginning of each cycle (1 cycle =28 days) while on treatment and 30 days beyond the last treatment for a maximum of 69 cycles (the most number of cycles any patient was treated on study)

Additional Information

Jeffery Raizer, MD

Northwestern University

Phone: 312-503-4724

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place