Trial Outcomes & Findings for Dose-Dense Temozolomide + Lapatinib for Recurrent Ependymoma (NCT NCT00826241)

Last Updated: 2019-03-22

Results Overview

Time to progression defined as progressive disease, toxicity at a level of severity that precludes the patient continuing on the protocol, or death. Progression is a 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).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

58 participants

Primary outcome timeframe

Assessed every two months till disease progression, up to 4 years

Results posted on

2019-03-22

Participant Flow

Participant milestones

Participant milestones
Measure	Temozolomide + Lapatinib Temozolomide starting dose 125 mg/m\^2 daily by mouth on days 1-7 \& 15-21 of a 28 day cycle. Lapatinib starting dose 1250 mg daily by mouth. Temozolomide: Starting dose 125 mg/m\^2 daily by mouth on days 1-7 \& 15-21 of a 28 day cycle. Lapatinib: Starting dose 1250 mg daily by mouth.
Overall Study STARTED	58
Overall Study COMPLETED	31
Overall Study NOT COMPLETED	27

Reasons for withdrawal

Reasons for withdrawal
Measure	Temozolomide + Lapatinib Temozolomide starting dose 125 mg/m\^2 daily by mouth on days 1-7 \& 15-21 of a 28 day cycle. Lapatinib starting dose 1250 mg daily by mouth. Temozolomide: Starting dose 125 mg/m\^2 daily by mouth on days 1-7 \& 15-21 of a 28 day cycle. Lapatinib: Starting dose 1250 mg daily by mouth.
Overall Study Withdrawal from Follow-up	1
Overall Study Withdrew consent	2
Overall Study Death	4
Overall Study Non-reportable(not qualify as Gr. 5 SAE)	1
Overall Study Non-compliance	1
Overall Study Progression of disease	1
Overall Study Patient refused follow-up	3
Overall Study Lost to Follow-up	9
Overall Study Could not obtain records	1
Overall Study Screen failure	2
Overall Study Pt unable to proceed to registration	1
Overall Study Pt opt not to proceed w/trmt	1

Baseline Characteristics

Dose-Dense Temozolomide + Lapatinib for Recurrent Ependymoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Temozolomide + Lapatinib n=58 Participants Temozolomide starting dose 125 mg/m\^2 daily by mouth on days 1-7 \& 15-21 of a 28 day cycle. Lapatinib starting dose 1250 mg daily by mouth. Temozolomide: Starting dose 125 mg/m\^2 daily by mouth on days 1-7 \& 15-21 of a 28 day cycle. Lapatinib: Starting dose 1250 mg daily by mouth.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	49 Participants n=5 Participants
Age, Categorical >=65 years	9 Participants n=5 Participants
Age, Continuous	46.77 years STANDARD_DEVIATION 15.15 • n=5 Participants
Sex: Female, Male Female	40 Participants n=5 Participants
Sex: Female, Male Male	18 Participants n=5 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	58 Participants n=5 Participants
Race/Ethnicity, Customized American Indian/Alaskan Native	1 Participants n=5 Participants
Race/Ethnicity, Customized Black	2 Participants n=5 Participants
Race/Ethnicity, Customized White	51 Participants n=5 Participants
Race/Ethnicity, Customized Unknown	3 Participants n=5 Participants
Race/Ethnicity, Customized Other	1 Participants n=5 Participants
Region of Enrollment United States	58 Participants n=5 Participants

PRIMARY outcome

Timeframe: Assessed every two months till disease progression, up to 4 years

Population: 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.

Outcome measures

Outcome measures
Measure	Temozolomide + Lapatinib n=50 Participants Temozolomide starting dose 125 mg/m\^2 daily by mouth on days 1-7 \& 15-21 of a 28 day cycle. Lapatinib starting dose 1250 mg daily by mouth. Temozolomide: Starting dose 125 mg/m\^2 daily by mouth on days 1-7 \& 15-21 of a 28 day cycle. Lapatinib: Starting dose 1250 mg daily by mouth.
Time to Progression	7.8 Months Interval 5.2 to 12.2

SECONDARY outcome

Timeframe: 4 weeks

Anti-tumor activity as determined by the overall response (Complete response (CR) or partial response (PR)) was assessed by the MacDonald criteria. Complete response is complete resolution of all lesions. The patient cannot be on any corticosteroids with the exception of adrenal replacement doses. Partial response is ≥50% reduction in the sum of products of all measurable lesions over baseline sum observed using the same techniques as baseline. The patient must be on a stable or decreased dose of corticosteroids to be evaluable for response.

Outcome measures

Outcome measures
Measure	Temozolomide + Lapatinib n=50 Participants Temozolomide starting dose 125 mg/m\^2 daily by mouth on days 1-7 \& 15-21 of a 28 day cycle. Lapatinib starting dose 1250 mg daily by mouth. Temozolomide: Starting dose 125 mg/m\^2 daily by mouth on days 1-7 \& 15-21 of a 28 day cycle. Lapatinib: Starting dose 1250 mg daily by mouth.
Number of Participants With an Overall Response (Complete Response or Partial Response) Assessed by the MacDonald Criteria Complete Response	2 Participants
Number of Participants With an Overall Response (Complete Response or Partial Response) Assessed by the MacDonald Criteria Partial Response	8 Participants

SECONDARY outcome

Timeframe: Date treatment consent signed to date off study, approximately 111 months and 26 days

Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

Outcome measures

Outcome measures
Measure	Temozolomide + Lapatinib n=50 Participants Temozolomide starting dose 125 mg/m\^2 daily by mouth on days 1-7 \& 15-21 of a 28 day cycle. Lapatinib starting dose 1250 mg daily by mouth. Temozolomide: Starting dose 125 mg/m\^2 daily by mouth on days 1-7 \& 15-21 of a 28 day cycle. Lapatinib: Starting dose 1250 mg daily by mouth.
Number of Participants With Serious and Non-Serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0)	50 Participants

Adverse Events

Temozolomide + Lapatinib

Serious events: 13 serious events

Other events: 50 other events

Deaths: 4 deaths

Serious adverse events

Serious adverse events
Measure	Temozolomide + Lapatinib n=50 participants at risk Temozolomide starting dose 125 mg/m\^2 daily by mouth on days 1-7 \& 15-21 of a 28 day cycle. Lapatinib starting dose 1250 mg daily by mouth. Temozolomide: Starting dose 125 mg/m\^2 daily by mouth on days 1-7 \& 15-21 of a 28 day cycle. Lapatinib: Starting dose 1250 mg daily by mouth.
Nervous system disorders Ataxia (incoordination)	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Gastrointestinal disorders Diarrhea	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Respiratory, thoracic and mediastinal disorders Dyspnea (shortness of breath)	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Blood and lymphatic system disorders Febrile neutropenia	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Gastrointestinal disorders Hemorrhage, GU : Bladder	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Surgical and medical procedures Hemorrhage/bleeding associated with surgery, intra-operative or postoperative	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Infections and infestations Infection	4.0% 2/50 • Number of events 4 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Infections and infestations Infection with normal ANC or Grade 1 or 2 neutrophils : Skin (cellulitis)	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Infections and infestations Infection with normal ANC or Grade 1 or 2 neutrophils : Urinary tract NOS	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Investigations Leukocytes (total WBC)	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Investigations Lymphopenia	4.0% 2/50 • Number of events 18 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Musculoskeletal and connective tissue disorders Muscle weakness, generalized or specific area (not due to neuropathy) : Extremity-lower	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Investigations Neutrophils/granulocytes (ANC/AGC)	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Musculoskeletal and connective tissue disorders Pain - Other (Specify, left hip)	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Investigations Platelets	4.0% 2/50 • Number of events 4 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Respiratory, thoracic and mediastinal disorders Pneumonitis/pulmonary infiltrates	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Skin and subcutaneous tissue disorders Pruritus/itching	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Respiratory, thoracic and mediastinal disorders Pulmonary/Upper Respiratory - Other (Specify, __)	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Secondary Malignancy - possibly related to cancer treatment (Specify,B-cell/large cell lymphoma)	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Vascular disorders Thrombosis/thrombus/embolism	4.0% 2/50 • Number of events 4 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.

Other adverse events

Other adverse events
Measure	Temozolomide + Lapatinib n=50 participants at risk Temozolomide starting dose 125 mg/m\^2 daily by mouth on days 1-7 \& 15-21 of a 28 day cycle. Lapatinib starting dose 1250 mg daily by mouth. Temozolomide: Starting dose 125 mg/m\^2 daily by mouth on days 1-7 \& 15-21 of a 28 day cycle. Lapatinib: Starting dose 1250 mg daily by mouth.
Metabolism and nutrition disorders Albumin, serum-low (hypoalbuminemia)	12.0% 6/50 • Number of events 20 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Investigations Alkaline phosphatase	14.0% 7/50 • Number of events 18 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Respiratory, thoracic and mediastinal disorders Allergic rhinitis (including sneezing, nasal stuffiness, postnasal drip)	6.0% 3/50 • Number of events 6 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Immune system disorders Allergy/Immunology - Other (Specify, environmental allergic dry cough)	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Investigations ALT, SGPT (serum glutamic pyruvic transaminase)	34.0% 17/50 • Number of events 54 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Investigations Amylase	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Metabolism and nutrition disorders Anorexia	20.0% 10/50 • Number of events 22 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Investigations AST, SGOT(serum glutamic oxaloacetic transaminase)	32.0% 16/50 • Number of events 50 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Nervous system disorders Ataxia (incoordination)	12.0% 6/50 • Number of events 14 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Ear and labyrinth disorders Auditory/Ear - Other (Specify, fluttering sensation)	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Ear and labyrinth disorders Auditory/Ear - Other (Specify, hearing loss; present at baseline)	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Investigations Bicarbonate, serum-low	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Investigations Bilirubin (hyperbilirubinemia)	8.0% 4/50 • Number of events 16 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Blood and lymphatic system disorders Blood/Bone Marrow - Other (Specify, BUN)	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Blood and lymphatic system disorders Blood/Bone Marrow - Other (Specify,elevated bilirubin)	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Respiratory, thoracic and mediastinal disorders Bronchospasm, wheezing	6.0% 3/50 • Number of events 6 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Injury, poisoning and procedural complications Bruising (in absence of Grade 3 or 4 thrombocytopenia)	4.0% 2/50 • Number of events 4 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Metabolism and nutrition disorders Calcium, serum-low (hypocalcemia)	14.0% 7/50 • Number of events 20 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Cardiac disorders Cardiac General - Other (Specify, sinus tachycardia)	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Eye disorders Cataract	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Musculoskeletal and connective tissue disorders Cervical spine-range of motion	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Investigations Cholesterol, serum-high (hypercholesteremia)	6.0% 3/50 • Number of events 6 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Nervous system disorders Cognitive disturbance	8.0% 4/50 • Number of events 8 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Psychiatric disorders Confusion	4.0% 2/50 • Number of events 4 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Gastrointestinal disorders Constipation	64.0% 32/50 • Number of events 82 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
General disorders Constitutional Symptoms - Other (Specify, constipation)	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
General disorders Constitutional Symptoms - Other (Specify, fatigue)	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
General disorders Constitutional Symptoms - Other (Specify, hyposmia: reduced ability to smell)	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
General disorders Constitutional Symptoms - Other (Specify,insomnia)	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Respiratory, thoracic and mediastinal disorders Cough	18.0% 9/50 • Number of events 18 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Investigations Creatinine	12.0% 6/50 • Number of events 22 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Endocrine disorders Cushingoid appearance (e.g., moon face, buffalo hump, centripetal obesity, cutaneous striae)	4.0% 2/50 • Number of events 4 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Skin and subcutaneous tissue disorders Dermatology/Skin - Other (Specify, _)	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Skin and subcutaneous tissue disorders Dermatology/Skin - Other (Specify,steroid-related acne)	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Skin and subcutaneous tissue disorders Dermatology/Skin - Other (Specify, paresthesia)	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Gastrointestinal disorders Diarrhea	38.0% 19/50 • Number of events 46 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Gastrointestinal disorders Distension/bloating, abdominal	2.0% 1/50 • Number of events 4 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Nervous system disorders Dizziness	10.0% 5/50 • Number of events 10 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Skin and subcutaneous tissue disorders Dry skin	6.0% 3/50 • Number of events 6 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Gastrointestinal disorders Dysphagia (difficulty swallowing)	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Respiratory, thoracic and mediastinal disorders Dyspnea (shortness of breath)	20.0% 10/50 • Number of events 24 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
General disorders Edema: head and neck	4.0% 2/50 • Number of events 4 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
General disorders Edema: limb	16.0% 8/50 • Number of events 18 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Reproductive system and breast disorders Erectile dysfunction	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Nervous system disorders Extrapyramidal/involuntary movement/restlessness	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Musculoskeletal and connective tissue disorders Extremity-lower (gait/walking)	36.0% 18/50 • Number of events 42 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
General disorders Fatigue (asthenia, lethargy, malaise)	78.0% 39/50 • Number of events 102 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
General disorders Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L)	8.0% 4/50 • Number of events 14 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Gastrointestinal disorders Flatulence	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Vascular disorders Flushing	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Gastrointestinal disorders Gastritis (including bile reflux gastritis)	4.0% 2/50 • Number of events 4 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Gastrointestinal disorders Gastrointestinal - Other (Specify, abdominal distension)	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Gastrointestinal disorders Gastrointestinal - Other (Specify, cramps in pelvis)	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Gastrointestinal disorders Gastrointestinal - Other (Specify,gastrointestinal pain (intermittent))	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Gastrointestinal disorders Gastrointestinal - Other (Specify, mucositis oral)	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Gastrointestinal disorders Gastrointestinal - Other (Specify, rectal discomfort)	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Gastrointestinal disorders Gastrointestinal - Other (Specify, stool incontinence)	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Metabolism and nutrition disorders Glucose, serum-high (hyperglycemia)	44.0% 22/50 • Number of events 86 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Metabolism and nutrition disorders Glucose, serum-low (hypoglycemia)	18.0% 9/50 • Number of events 24 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Skin and subcutaneous tissue disorders Hair loss/alopecia (scalp or body)	8.0% 4/50 • Number of events 8 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Ear and labyrinth disorders Hearing: patients with/without baseline audiogram and enrolled in a monitoring program	4.0% 2/50 • Number of events 4 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Ear and labyrinth disorders Hearing: patients without baseline audiogram and not enrolled in a monitoring program	4.0% 2/50 • Number of events 4 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Gastrointestinal disorders Heartburn/dyspepsia	4.0% 2/50 • Number of events 4 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Investigations Hemoglobin	50.0% 25/50 • Number of events 190 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Gastrointestinal disorders Hemorrhage, GI : Lower GI NOS	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Gastrointestinal disorders Hemorrhage, GI : Oral cavity	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Gastrointestinal disorders Hemorrhage, GI : Rectum	4.0% 2/50 • Number of events 4 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Gastrointestinal disorders Hemorrhage/Bleeding - Other (Specify, gums)	4.0% 2/50 • Number of events 4 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Respiratory, thoracic and mediastinal disorders Hemorrhage/Bleeding - Other (Specify, nose)	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Surgical and medical procedures Hemorrhage/bleeding associated with surgery, intra-operative or postoperative	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Vascular disorders Hot flashes/flushes	4.0% 2/50 • Number of events 4 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Vascular disorders Hypertension	8.0% 4/50 • Number of events 8 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Vascular disorders Hypotension	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Gastrointestinal disorders Incontinence, anal	8.0% 4/50 • Number of events 8 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Renal and urinary disorders Incontinence, urinary	12.0% 6/50 • Number of events 14 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Infections and infestations Infection - Other (Specify, bronchial infection)	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Infections and infestations Infection - Other (Specify,Other, toe fungal)	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Infections and infestations Infection - Other (Specify,shingles)	6.0% 3/50 • Number of events 6 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Infections and infestations Infection - Other (Specify, Varicella Zoster)	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Infections and infestations Infection with normal ANC or Grade 1 or 2 neutrophils : Esophagus	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Infections and infestations Infection with normal ANC or Grade 1 or 2 neutrophils : External ear (otitis externa)	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Infections and infestations Infection with normal ANC or Grade 1 or 2 neutrophils	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Infections and infestations Infection with normal ANC or Grade 1 or 2 neutrophils : Skin (cellulitis)	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Infections and infestations Infection with normal ANC or Grade 1 or 2 neutrophils : Upper airway NOS	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Infections and infestations Infection with normal ANC or Grade 1 or 2 neutrophils : Urinary tract NOS	8.0% 4/50 • Number of events 10 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Infections and infestations Infection with unknown ANC : Bladder (urinary)	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Infections and infestations Infection with unknown ANC : Urinary tract NOS	4.0% 2/50 • Number of events 4 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Psychiatric disorders Insomnia	14.0% 7/50 • Number of events 14 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Blood and lymphatic system disorders Leukocytes (total WBC)	60.0% 30/50 • Number of events 352 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Reproductive system and breast disorders Libido	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Investigations Lipase	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Blood and lymphatic system disorders Lymphatics - Other (Specify, left thigh)	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Blood and lymphatic system disorders Lymphatics - Other (Specify,mild peripheral edema)	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Investigations Lymphopenia	70.0% 35/50 • Number of events 444 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Metabolism and nutrition disorders Magnesium, serum-low (hypomagnesemia)	6.0% 3/50 • Number of events 8 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Nervous system disorders Memory impairment	22.0% 11/50 • Number of events 22 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Metabolism and nutrition disorders Metabolic/Laboratory - Other (Specify, Akaline Phosphatase Serum Low)	4.0% 2/50 • Number of events 4 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Metabolism and nutrition disorders Metabolic/Laboratory - Other (Specify, Albumin serum high)	10.0% 5/50 • Number of events 10 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Metabolism and nutrition disorders Metabolic/Laboratory - Other (Specify,alkaline phosphatase count low)	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Metabolism and nutrition disorders Metabolic/Laboratory - Other (Specify,amylase serum low)	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Metabolism and nutrition disorders Metabolic/Laboratory - Other (Specify,AST-SGOT serum low)	6.0% 3/50 • Number of events 6 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Metabolism and nutrition disorders Metabolic/Laboratory - Other (Specify, BUN)	2.0% 1/50 • Number of events 6 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Metabolism and nutrition disorders Metabolic/Laboratory - Other (Specify, BUN count increased)	4.0% 2/50 • Number of events 6 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Metabolism and nutrition disorders Metabolic/Laboratory - Other (Specify, BUN serum high)	6.0% 3/50 • Number of events 12 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Metabolism and nutrition disorders Metabolic/Laboratory - Other (Specify, BUN serum low)	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Metabolism and nutrition disorders Metabolic/Laboratory - Other (Specify, carbon dioxide)	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Metabolism and nutrition disorders Metabolic/Laboratory - Other (Specify, carbon dioxide count increased)	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Metabolism and nutrition disorders Metabolic/Laboratory - Other (Specify, carbon dioxide serum high)	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Metabolism and nutrition disorders Metabolic/Laboratory - Other (Specify, chloride count decreased)	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Metabolism and nutrition disorders Metabolic/Laboratory - Other (Specify, chloride serum high)	10.0% 5/50 • Number of events 12 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Metabolism and nutrition disorders Metabolic/Laboratory - Other (Specify, chloride serum low)	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Metabolism and nutrition disorders Metabolic/Laboratory - Other (Specify, CO2 count increased)	4.0% 2/50 • Number of events 4 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Metabolism and nutrition disorders Metabolic/Laboratory - Other (Specify, CO2 high serum)	12.0% 6/50 • Number of events 18 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Metabolism and nutrition disorders Metabolic/Laboratory - Other (Specify, creatinine count decreased)	6.0% 3/50 • Number of events 6 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Metabolism and nutrition disorders Metabolic/Laboratory - Other (Specify, creatinine serum low)	14.0% 7/50 • Number of events 16 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Metabolism and nutrition disorders Metabolic/Laboratory - Other (Specify, CSF Total Nucleated Cells Increased)	4.0% 2/50 • Number of events 4 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Metabolism and nutrition disorders Metabolic/Laboratory - Other (Specify, hyperalbumin)	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Metabolism and nutrition disorders Metabolic/Laboratory - Other (Specify, hyperphosphatemia)	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Metabolism and nutrition disorders Metabolic/Laboratory - Other (Specify, LDH)	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Metabolism and nutrition disorders Metabolic/Laboratory - Other (Specify, LDH serum increased)	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Metabolism and nutrition disorders Metabolic/Laboratory - Other (Specify, LDH count decreased)	4.0% 2/50 • Number of events 4 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Metabolism and nutrition disorders Metabolic/Laboratory - Other (Specify, LDH count increased)	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Metabolism and nutrition disorders Metabolic/Laboratory - Other (Specify, LDH serum high)	6.0% 3/50 • Number of events 8 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Metabolism and nutrition disorders Metabolic/Laboratory - Other (Specify, LDH serum low)	4.0% 2/50 • Number of events 10 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Metabolism and nutrition disorders Metabolic/Laboratory - Other (Specify, phosphorous serum high)	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Metabolism and nutrition disorders Metabolic/Laboratory - Other (Specify, protein count decreased)	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Metabolism and nutrition disorders Metabolic/Laboratory - Other (Specify, protein serum low)	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Metabolism and nutrition disorders Metabolic/Laboratory - Other (Specify, SGOT decreased count)	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Metabolism and nutrition disorders Metabolic/Laboratory - Other (Specify, total protein serum low)	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Metabolism and nutrition disorders Metabolic/Laboratory - Other (Specify, uric acid serum low)	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Metabolism and nutrition disorders Metabolic/Laboratory - Other (Specify, vitamin B12 deficiency)	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Psychiatric disorders Mood alteration :	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Psychiatric disorders Mood alteration : Agitation	4.0% 2/50 • Number of events 4 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Psychiatric disorders Mood alteration : Anxiety	18.0% 9/50 • Number of events 18 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Psychiatric disorders Mood alteration : Depression	12.0% 6/50 • Number of events 14 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Gastrointestinal disorders Mucositis/stomatitis (clinical exam) :	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Gastrointestinal disorders Mucositis/stomatitis (clinical exam) : Oral cavity	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Gastrointestinal disorders Mucositis/stomatitis (functional/symptomatic) : Oral cavity	4.0% 2/50 • Number of events 4 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Musculoskeletal and connective tissue disorders Muscle weakness, generalized or specific area (not due to neuropathy)	2.0% 1/50 • Number of events 4 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Musculoskeletal and connective tissue disorders Muscle weakness, generalized or specific area (not due to neuropathy) : Extremity-lower	14.0% 7/50 • Number of events 16 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Musculoskeletal and connective tissue disorders Muscle weakness, generalized or specific area (not due to neuropathy) : Extremity-upper	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Musculoskeletal and connective tissue disorders Muscle weakness, generalized or specific area (not due to neuropathy) : Facial	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Musculoskeletal and connective tissue disorders Muscle weakness, generalized or specific area (not due to neuropathy) : Left-sided	4.0% 2/50 • Number of events 4 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Musculoskeletal and connective tissue disorders Muscle weakness, generalized or specific area (not due to neuropathy) : Right-sided	10.0% 5/50 • Number of events 10 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Musculoskeletal and connective tissue disorders Muscle weakness, generalized or specific area (not due to neuropathy) : Whole body/generalized	6.0% 3/50 • Number of events 6 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Musculoskeletal and connective tissue disorders Musculoskeletal/Soft Tissue - Other (Specify, difficulty walking)	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Musculoskeletal and connective tissue disorders Musculoskeletal/Soft Tissue - Other (Specify, intermittent back pain)	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Musculoskeletal and connective tissue disorders Musculoskeletal/Soft Tissue - Other (Specify, left hand)	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Musculoskeletal and connective tissue disorders Musculoskeletal/Soft Tissue - Other (Specify, lower extremity)	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Musculoskeletal and connective tissue disorders Musculoskeletal/Soft Tissue - Other (Specify, paresthesia, left hand (carpal tunnel type syndrome)	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Musculoskeletal and connective tissue disorders Musculoskeletal/Soft Tissue - Other (Specify, right back tightness)	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Skin and subcutaneous tissue disorders Nail changes	4.0% 2/50 • Number of events 4 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Respiratory, thoracic and mediastinal disorders Nasal cavity/paranasal sinus reactions	6.0% 3/50 • Number of events 6 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Gastrointestinal disorders Nausea	64.0% 32/50 • Number of events 82 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Nervous system disorders Neurology - Other (Specify, __)	24.0% 12/50 • Number of events 32 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Nervous system disorders Neuropathy: cranial : CN VII Motor-face; Sensory-taste	4.0% 2/50 • Number of events 4 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Nervous system disorders Neuropathy: cranial : CN VIII Hearing and balance	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Nervous system disorders Neuropathy: motor	12.0% 6/50 • Number of events 12 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Nervous system disorders Neuropathy: sensory	44.0% 22/50 • Number of events 52 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Investigations Neutrophils/granulocytes (ANC/AGC)	34.0% 17/50 • Number of events 154 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Reproductive system and breast disorders Obstruction, GU : Prostate	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Eye disorders Ocular/Visual - Other (Specify, Dysconjugate gaze. Present after surgery.)	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Eye disorders Ocular/Visual - Other (Specify, left hemaniopsia)	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Eye disorders Ocular/Visual - Other (Specify, vision loss left eye)	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Eye disorders Ocular/Visual - Other (Specify, visual impairment)	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Eye disorders Ophthalmoplegia/diplopia (double vision)	4.0% 2/50 • Number of events 4 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Infections and infestations Opportunistic infection associated with >=Grade 2 Lymphopenia	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
General disorders Pain	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Musculoskeletal and connective tissue disorders Pain - Other (Specify, back and right arm)	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Nervous system disorders Pain - Other (Specify, headaches)	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Musculoskeletal and connective tissue disorders Pain - Other (Specify, joint pain)	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Musculoskeletal and connective tissue disorders Pain - Other (Specify, left anterior iliac spine)	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Musculoskeletal and connective tissue disorders Pain - Other (Specify, left leg)	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Musculoskeletal and connective tissue disorders Pain - Other (Specify, left sacrum pain)	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Musculoskeletal and connective tissue disorders Pain - Other (Specify, leg pain)	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Musculoskeletal and connective tissue disorders Pain - Other (Specify, musculoskeletal-back)	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Nervous system disorders Pain - Other (Specify, neuralgia)	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Skin and subcutaneous tissue disorders Pain - Other (Specify, pain in the rash area chest and the back)	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Musculoskeletal and connective tissue disorders Pain - Other (Specify, pain-pelvis)	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Musculoskeletal and connective tissue disorders Pain - Other (Specify, RUQ)	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Musculoskeletal and connective tissue disorders Pain - Other (Specify, severe pain left thigh)	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Gastrointestinal disorders Pain - Other (Specify, stomach pain)	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Gastrointestinal disorders Pain : Abdomen NOS	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Musculoskeletal and connective tissue disorders Pain : Back	26.0% 13/50 • Number of events 28 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Musculoskeletal and connective tissue disorders Pain : Bone	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Reproductive system and breast disorders Pain : Breast	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Musculoskeletal and connective tissue disorders Pain : Chest/thorax NOS	6.0% 3/50 • Number of events 6 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Musculoskeletal and connective tissue disorders Pain : Extremity-limb	8.0% 4/50 • Number of events 8 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Nervous system disorders Pain : Head/headache	34.0% 17/50 • Number of events 38 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Musculoskeletal and connective tissue disorders Pain : Joint	4.0% 2/50 • Number of events 4 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Musculoskeletal and connective tissue disorders Pain : Muscle	4.0% 2/50 • Number of events 4 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Musculoskeletal and connective tissue disorders Pain : Neck	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Gastrointestinal disorders Pain : Oral cavity	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
General disorders Pain : Pain NOS	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Respiratory, thoracic and mediastinal disorders Pain : Throat/pharynx/larynx	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pain : Tumor pain	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Cardiac disorders Palpitations	4.0% 2/50 • Number of events 4 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Metabolism and nutrition disorders Phosphate, serum-low (hypophosphatemia)	8.0% 4/50 • Number of events 22 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Investigations Platelets	46.0% 23/50 • Number of events 174 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Investigations Potassium, serum-high (hyperkalemia)	6.0% 3/50 • Number of events 6 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Metabolism and nutrition disorders Potassium, serum-low (hypokalemia)	6.0% 3/50 • Number of events 12 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Skin and subcutaneous tissue disorders Pruritus/itching	18.0% 9/50 • Number of events 22 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Respiratory, thoracic and mediastinal disorders Pulmonary/Upper Respiratory - Other (Specify, sinus congestion)	2.0% 1/50 • Number of events 4 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Nervous system disorders Pyramidal tract dysfunction	18.0% 9/50 • Number of events 18 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Skin and subcutaneous tissue disorders Rash/desquamation	30.0% 15/50 • Number of events 48 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Skin and subcutaneous tissue disorders Rash: acne/acneiform	32.0% 16/50 • Number of events 42 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Skin and subcutaneous tissue disorders Rash: erythema multiforme (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis)	8.0% 4/50 • Number of events 8 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Skin and subcutaneous tissue disorders Rash: hand-foot skin reaction	4.0% 2/50 • Number of events 4 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Renal and urinary disorders Renal/Genitourinary - Other (Specify, urinary tract infection)	2.0% 1/50 • Number of events 4 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
General disorders Rigors/chills	4.0% 2/50 • Number of events 4 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Nervous system disorders Seizure	6.0% 3/50 • Number of events 8 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Skin and subcutaneous tissue disorders Skin breakdown/decubitus ulcer	6.0% 3/50 • Number of events 6 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Metabolism and nutrition disorders Sodium, serum-high (hypernatremia)	10.0% 5/50 • Number of events 10 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Metabolism and nutrition disorders Sodium, serum-low (hyponatremia)	10.0% 5/50 • Number of events 18 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Nervous system disorders Speech impairment (e.g., dysphasia or aphasia)	10.0% 5/50 • Number of events 10 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Cardiac disorders Supraventricular and nodal arrhythmia : Atrial fibrillation	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Nervous system disorders Syncope (fainting)	4.0% 2/50 • Number of events 4 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
General disorders Syndromes - Other (Specify, tremors; left hand)	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Eye disorders Taste alteration (dysgeusia)	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Vascular disorders Thrombosis/embolism (vascular access-related)	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Vascular disorders Thrombosis/thrombus/embolism	4.0% 2/50 • Number of events 4 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Endocrine disorders Thyroid function, high (hyperthyroidism, thyrotoxicosis)	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Endocrine disorders Thyroid function, low (hypothyroidism)	4.0% 2/50 • Number of events 4 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Ear and labyrinth disorders Tinnitus	8.0% 4/50 • Number of events 8 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Metabolism and nutrition disorders Triglyceride, serum-high (hypertriglyceridemia)	4.0% 2/50 • Number of events 4 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Metabolism and nutrition disorders Uric acid, serum-high (hyperuricemia)	14.0% 7/50 • Number of events 26 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Renal and urinary disorders Urinary frequency/urgency	14.0% 7/50 • Number of events 14 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Renal and urinary disorders Urinary retention (including neurogenic bladder)	12.0% 6/50 • Number of events 12 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Reproductive system and breast disorders Vaginal dryness	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Cardiac disorders Valvular heart disease	2.0% 1/50 • Number of events 4 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Eye disorders Vision-blurred vision	14.0% 7/50 • Number of events 14 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Eye disorders Vision-flashing lights/floaters	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Respiratory, thoracic and mediastinal disorders Voice changes/dysarthria (e.g., hoarseness, loss or alteration in voice, laryngitis)	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Gastrointestinal disorders Vomiting	20.0% 10/50 • Number of events 24 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Investigations Weight loss	18.0% 9/50 • Number of events 18 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.
Injury, poisoning and procedural complications Wound complication, non-infectious	2.0% 1/50 • Number of events 2 • Date treatment consent signed to date off study, approximately 111 months and 26 days. 8 patients were not evaluable/replaced: 2 - withdrew,1 - non-compliant, 2 - screen failures, 1 - could not obtain records, 1 - opted not to proceed with treatment, and 1 - unable to proceed to registration.

Additional Information

Dr. Mark Gilbert

National Cancer Institute

Phone: 240-760-6023

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place