Docetaxel, Bevacizumab and Androgen Deprivation Therapy After Definitive Local Therapy for Prostate Cancer

• Sponsor: Dana-Farber Cancer Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT00658697
• Collaborator: Brigham and Women's Hospital (Other), Beth Israel Deaconess Medical Center (Other), Genentech, Inc. (Industry)
• Enrollment: 42
• Locations: 3
• Arm: 1
• Duration (Months): 84
• Patients Per Site: 14
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

In this research study, we aim to evaluate the feasibility, toxicity and efficacy of early multimodality systemic therapy (a combination of docetaxe, bevacizumab, and androgen deprivation therapy(ADT) in men with biochemical recurrence (BCR) or who have a rising Prostate Specific Antigen (PSA) after treatment of their prostate cancer with surgery or radiation)

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer	Drug: Docetaxel; Drug: Bevacizumab; Drug: ADT; Drug: Bicalutamide	Phase 2

Detailed Description

A single arm phase 2 study designed to evaluate the rate of patients free from Prostate Specific Antigen (PSA) progression (TTP) one year after completing ADT for men with BCR after definitive local therapy for prostate cancer.

The null and alternative TTP rate were 41% and 60% respectively. A sample size of 42 would provide 80% power to detect the difference with a 2-sided type I error rate of 0.05.'

The primary objective was to evaluate the proportion of patients free from PSA progression after completing one year of ADT

The secondary objectives included

1. PSA response (< 0.2 ng/mL and < 0.01) at completion of docetaxel/bevacizumab, at completion of ADT and one year off ADT

2. Correlation of PSA response and TTP

3. Toxicity

4. Testosterone recovery at 6, 12 months off ADT

Treatment schedule details are as follows:

• Each treatment cycle lasts three weeks. During the first three months, participants will receive the Avastin and docetaxel on day 1 of each three-week cycle for a total of four doses of docetaxel/Avastin. Avastin and docetaxel are administered intravenously. The Avastin will continue to be given every three weeks after the docetaxel is completed for a total of 17 doses (one year) of Avastin therapy.

• Participants will receive zoladex (or lupron) on day 1 of the first cycle and then every 3 months for a total of 18 months. Zoladex is administered subcutaneously and Lupron is administered intramuscularly.

• Bicalutamide pills will be started at the completion of docetaxel chemotherapy (start of month 4) and will be taken once daily until hormone therapy is completed (total of 15 months).

• During all treatment cycles, the participant will have a physical exam and will be asked questions about their general health and specific questions about any problems they might be experiencing. Blood work will be performed every three weeks for the first three months and then every three months while on hormone therapy and during follow-up.

• After the final treatment participants will have a follow-up visit every three months for the first two years, every 4 months for the third year and every 6 months for years 4 and 5.

Study Design

• Study Type: Interventional
• Actual Enrollment: 42 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Trial of Avastin, Docetaxel and Androgen Deprivation Followed by Continued Avastin and Androgen Deprivation for Men With a Rising Prostate Specific Antigen (PSA) After Local Therapy
• Study Start Date: Jun 1, 2008
• Actual Primary Completion Date: Sep 1, 2014
• Actual Study Completion Date: Jun 1, 2015

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Docetaxel, Bevacizumab, and ADT Docetaxel: Intravenously given at 75 mg/m2 on day 1 of every 3 weeks for 4 cycles Bevacizumab: Intravenously given at (15 mg/kg) on day 1 of every 3 weeks for 8 cycles ADT or Luteinizing hormone-releasing hormone agonist (LHRH): Either subcutaneously or intramuscularly every three months for a total of 6 doses (total of 18 months) Bicalutamide: Oral Bicalutamide on day 84 once daily (after completing docetaxel, at 3 month) at dose of 50 mg for a total 15 months (4-18 months)

Drug: Docetaxel; Intravenously given at 75 mg/m2 on day 1 of every 3 weeks for 4 cycles; Other Names: Taxotere, Docecad ; Drug: Bevacizumab; Intravenously given at (15 mg/kg) on day 1 of every 3 weeks for 8 cycles; Other Names: Avastin ; Drug: ADT; Either subcutaneously or intramuscularly every three months for a total of 6 doses (total of 18 months); Other Names: Lupron or Zoladex ; Drug: Bicalutamide; Starting on day 84 orally once daily until hormone therapy is completed; Other Names: Casodex, Cosudex, Calutide, Kalumid

Outcome Measures

Primary Outcome Measures

1. Prostate-Specific Antigen (PSA) Progression at 1 Year After Completing Androgen Deprivation Therapy (ADT) [participants were followed for the duration of the study, an average of 2 years]

   For prostatectomy patients: at least two serial rising PSA from treatment nadir and PSA > 0.2 ng/mL. For patient receiving radiation therapy alone as primary local therapy, at least two serial rising PSA from treatment nadir and PSA >2.0 ng/mL. Any new site of metastatic disease on imagining would be considered progression regardless of PSA value Clinical assessments (Vitals, Physical Exam, Performance Status, PSA and testosterone) were performed every 3 months starting at completion of hormone therapy until PSA progression.

Secondary Outcome Measures

1. Proportion of Patients With PSA Responses at One Year After the Completion of ADT [1 year + 3 month off last ADT injection]

   The PSA response was defined using two cut-offs: PSA <0.2 ng/mL or PSA <0.01 ng/mL at the one year after completion of ADT.

2. Time to PSA Progression (TTP) [participants were followed for the duration of the study, an average of 2 years]

   For prostatectomy patients: at least two serial rising PSA from treatment nadir and PSA > 0.2 ng/mL. For patient receiving radiation therapy alone as primary local therapy, at least two serial rising PSA from treatment nadir and PSA > 2.0 ng/mL. Any new site of metastatic disease on imagining would be considered progression regardless of PSA value

3. Testosterone Recovery [2 years]

   Testosterone recovery was defined as >100 or within DFCI institute normal range (240-950) at one year after the completion of ADT

4. Toxicity [Assessed each cycle throughout treatment form time of first dose to 30 days post-treatment, up to 2 years]

   Treatment related adverse events were graded based on CTCAE v. 3.0.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• 18 years of age or older

• History of biopsy documented prostate cancer (any Gleason score)

• Past treatment with prostatectomy with our without salvage prostate/pelvic radiation or primary radiation

• If past prostatectomy, pathologic stage no greater than T1-3, N1, M0

• PSA recurrence with PSAdt 8 months or less. There is no minimum PSA for prostatectomy patients. For patients treated with primary radiation therapy PSA should be 2.0ng/ml or greater

• No evidence of recurrent disease on exam, bone scan, CT/MRI abdomen/pelvis on CXR

• Prior ADT allowed if less than 6 months and testosterone recovered to within 50 units of normal range

• ECOG Performance status of 0-1

• Absolute neutrophil count of 1,500 mm3 or greater

• Platelet Count 100,000 mm3 or greater

• Total bilirubin within normal limits

• HG 8gm/dl or greater

• Testosterone within 50 units of normal range

• No history of bleeding or thromboses within the last 12 months that required medical intervention

Exclusion Criteria:

• History of cancer within 5 years, other than prostate cancer and non-melanoma skin cancer

• Medical condition requiring concomitant corticosteroids

• Active infection

• Prior chemotherapy

• Neuropathy requiring medical therapy

• Documented local recurrence or metastatic prostate cancer

• Inability to comply with study and/or follow-up procedures

• Life expectancy of less than 2 years

• Current, recent (within 4 weeks of first infusion of this study), or planned participation in an experimental drug study other than a Genentech-sponsored Avastin cancer study

• Inadequately controlled hypertension

• Any prior history of hypertensive crisis or hypertensive encephalopathy

• NYHA Grade II or greater congestive heart failure

• History of myocardial infarction or unstable angina within 12 months prior to study enrollment

• History of stroke or transient ischemic attack at any time

• Known CNS disease

• Significant vascular disease

• Symptomatic peripheral vascular disease

• Evidence of bleeding diathesis or coagulopathy

• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study enrollment or anticipation of need for major surgical procedure during the course of the study

• Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to enrollment

• History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment

• Serious, non-healing wound, ulcer, or bone fracture

• Proteinuria at screening

• Known hypersensitivity to any component of Avastin

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Maryland - Greenebaum Cancer Center	Baltimore	Maryland	United States	21201
2	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02115
3	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02115

Sponsors and Collaborators

• Dana-Farber Cancer Institute
• Brigham and Women's Hospital
• Beth Israel Deaconess Medical Center
• Genentech, Inc.

Investigators

• Principal Investigator: Mary-Ellen Taplin, MD, Dana-Farber Cancer Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Mary-Ellen Taplin, MD, Associate Professor of Medicine, HMS, Dana-Farber Cancer Institute
• ClinicalTrials.gov Identifier: NCT00658697
• Other Study ID Numbers: 08-004
• First Posted: Apr 15, 2008
• Last Update Posted: May 25, 2017
• Last Verified: Apr 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Mary-Ellen Taplin, MD, Associate Professor of Medicine, HMS, Dana-Farber Cancer Institute: Rising PSA; androgen deprivation; bevacizumab (avastin); docetaxel; lupron; zoladex; bicalutamide
• Additional relevant MeSH terms: Prostatic Neoplasms; Bevacizumab; Docetaxel; Bicalutamide

Study Results

Participant Flow

Recruitment Details	42 patients were enrolled between June 2, 2008 to December 14, 2010 at Dana Farber Cancer Institute and University of Michigan. One patient never started any study treatment, and was excluded from analysis.

Arm/Group Title	Docetaxel, Bevacizumab, and ADT
Arm/Group Description	Docetaxel: Intravenously given at 75 mg/m2 on day 1 of every 3 weeks for 4 cycles Bevacizumab: Intravenously given at (15 mg/kg) on day 1 of every 3 weeks for 8 cycles ADT or Luteinizing hormone-releasing hormone agonist (LHRH): Either subcutaneously or intramuscularly every three months for a total of 6 doses (total of 18 months) Bicalutamide: Oral Bicalutamide on day 84 once daily (after completing docetaxel, at 3 month) at dose of 50 mg for a total 15 months (4-18 months) Docetaxel Bevacizumab: intravenously given at (15 mg/kg) on day 1 of every 3 weeks for 8 cycles ADT: Either subcutaneously or intramuscularly every three months for a total of 6 doses (total of 18 months) Bicalutamide: Starting on day 84 orally once daily until hormone therapy is completed
Period Title: Overall Study
STARTED	41
COMPLETED	41
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Docetaxel, Bevacizumab, and Androgen Deprivation Therapy (ADT)
Arm/Group Description	Docetaxel: Intravenously given at 75 mg/m2 on day 1 of every 3 weeks for 4 cycles Bevacizumab: Intravenously given at (15 mg/kg) on day 1 of every 3 weeks for 8 cycles Androgen deprivation therapy (ADT) or Luteinizing hormone-releasing hormone agonist (LHRH): Either subcutaneously or intramuscularly every three months for a total of 6 doses (total of 18 months) Bicalutamide: Oral Bicalutamide on day 84 once daily (after completing docetaxel, at 3 month) at dose of 50 mg for a total 15 months (4-18 months) Docetaxel Bevacizumab: intravenously given at (15 mg/kg) on day 1 of every 3 weeks for 8 cycles ADT: Either subcutaneously or intramuscularly every three months for a total of 6 doses (total of 18 months) Bicalutamide: Starting on day 84 orally once daily until hormone therapy is completed
Overall Participants	41
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	58
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	41 100%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 2.4%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	5 12.2%
White	35 85.4%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	41 100%

Outcome Measures

1. Secondary Outcome

Title	Proportion of Patients With PSA Responses at One Year After the Completion of ADT
Description	The PSA response was defined using two cut-offs: PSA <0.2 ng/mL or PSA <0.01 ng/mL at the one year after completion of ADT.
Time Frame	1 year + 3 month off last ADT injection

Outcome Measure Data

Analysis Population Description

The analysis comprised of all patients received at least one treatment and had PSA data available* for the assessment of PSA responses at one year after completing ADT *Note excluded 5 patients started treatments but had no PSA information at one year.

Arm/Group Title	Docetaxel, Bevacizumab, and ADT
Arm/Group Description	Docetaxel: Intravenously given at 75 mg/m2 on day 1 of every 3 weeks for 4 cycles Bevacizumab: Intravenously given at (15 mg/kg) on day 1 of every 3 weeks for 8 cycles ADT or Luteinizing hormone-releasing hormone agonist (LHRH): Either subcutaneously or intramuscularly every three months for a total of 6 doses (total of 18 months) Bicalutamide: Oral Bicalutamide on day 84 once daily (after completing docetaxel, at 3 month) at dose of 50 mg for a total 15 months (4-18 months) Docetaxel: Intravenously given at 75 mg/m2 on day 1 of every 3 weeks for 4 cycles Bevacizumab: Intravenously given at (15 mg/kg) on day 1 of every 3 weeks for 8 cycles ADT: Either subcutaneously or intramuscularly every three months for a total of 6 doses (total of 18 months) Bicalutamide: Starting on day 84 orally once daily until hormone therapy is completed
Measure Participants	36
PSA <0.2 ng/mL	44 107.3%
PSA <=0.01 ng/mL	25 61%

2. Secondary Outcome

Title	Time to PSA Progression (TTP)
Description	For prostatectomy patients: at least two serial rising PSA from treatment nadir and PSA > 0.2 ng/mL. For patient receiving radiation therapy alone as primary local therapy, at least two serial rising PSA from treatment nadir and PSA > 2.0 ng/mL. Any new site of metastatic disease on imagining would be considered progression regardless of PSA value
Time Frame	participants were followed for the duration of the study, an average of 2 years

Outcome Measure Data

Analysis Population Description

the analysis dataset is comprised of all treated patients

Arm/Group Title	Docetaxel, Bevacizumab, and ADT
Arm/Group Description	Docetaxel: Intravenously given at 75 mg/m2 on day 1 of every 3 weeks for 4 cycles Bevacizumab: Intravenously given at (15 mg/kg) on day 1 of every 3 weeks for 8 cycles ADT or Luteinizing hormone-releasing hormone agonist (LHRH): Either subcutaneously or intramuscularly every three months for a total of 6 doses (total of 18 months) Bicalutamide: Oral Bicalutamide on day 84 once daily (after completing docetaxel, at 3 month) at dose of 50 mg for a total 15 months (4-18 months) Docetaxel: Intravenously given at 75 mg/m2 on day 1 of every 3 weeks for 4 cycles Bevacizumab: Intravenously given at (15 mg/kg) on day 1 of every 3 weeks for 8 cycles ADT: Either subcutaneously or intramuscularly every three months for a total of 6 doses (total of 18 months) Bicalutamide: Starting on day 84 orally once daily until hormone therapy is completed
Measure Participants	41
Median (95% Confidence Interval) [months]	27.5

3. Secondary Outcome

Title	Testosterone Recovery
Description	Testosterone recovery was defined as >100 or within DFCI institute normal range (240-950) at one year after the completion of ADT
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

All treated patients with assessable testosterone level data

Arm/Group Title	Docetaxel, Bevacizumab, and ADT
Arm/Group Description	Docetaxel: Intravenously given at 75 mg/m2 on day 1 of every 3 weeks for 4 cycles Bevacizumab: Intravenously given at (15 mg/kg) on day 1 of every 3 weeks for 8 cycles ADT or Luteinizing hormone-releasing hormone agonist (LHRH): Either subcutaneously or intramuscularly every three months for a total of 6 doses (total of 18 months) Bicalutamide: Oral Bicalutamide on day 84 once daily (after completing docetaxel, at 3 month) at dose of 50 mg for a total 15 months (4-18 months) Docetaxel: Intravenously given at 75 mg/m2 on day 1 of every 3 weeks for 4 cycles Bevacizumab: Intravenously given at (15 mg/kg) on day 1 of every 3 weeks for 8 cycles ADT: Either subcutaneously or intramuscularly every three months for a total of 6 doses (total of 18 months) Bicalutamide: Starting on day 84 orally once daily until hormone therapy is completed
Measure Participants	35
Testosterone >=100 ng/mL	83 202.4%
Testosterone >=240 ng/mL	35 85.4%

4. Primary Outcome

Title	Prostate-Specific Antigen (PSA) Progression at 1 Year After Completing Androgen Deprivation Therapy (ADT)
Description	For prostatectomy patients: at least two serial rising PSA from treatment nadir and PSA > 0.2 ng/mL. For patient receiving radiation therapy alone as primary local therapy, at least two serial rising PSA from treatment nadir and PSA >2.0 ng/mL. Any new site of metastatic disease on imagining would be considered progression regardless of PSA value Clinical assessments (Vitals, Physical Exam, Performance Status, PSA and testosterone) were performed every 3 months starting at completion of hormone therapy until PSA progression.
Time Frame	participants were followed for the duration of the study, an average of 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Docetaxel, Bevacizumab, and ADT
Arm/Group Description	Docetaxel: Intravenously given at 75 mg/m2 on day 1 of every 3 weeks for 4 cycles Bevacizumab: Intravenously given at (15 mg/kg) on day 1 of every 3 weeks for 8 cycles ADT or Luteinizing hormone-releasing hormone agonist (LHRH): Either subcutaneously or intramuscularly every three months for a total of 6 doses (total of 18 months) Bicalutamide: Oral Bicalutamide on day 84 once daily (after completing docetaxel, at 3 month) at dose of 50 mg for a total 15 months (4-18 months) Docetaxel Bevacizumab: intravenously given at (15 mg/kg) on day 1 of every 3 weeks for 8 cycles ADT: Either subcutaneously or intramuscularly every three months for a total of 6 doses (total of 18 months) Bicalutamide: Starting on day 84 orally once daily until hormone therapy is completed
Measure Participants	41
Number (95% Confidence Interval) [percentage of participants with data]	98 239%

5. Secondary Outcome

Title	Toxicity
Description	Treatment related adverse events were graded based on CTCAE v. 3.0.
Time Frame	Assessed each cycle throughout treatment form time of first dose to 30 days post-treatment, up to 2 years

Outcome Measure Data

Analysis Population Description

All patients received at least one study therapies

Arm/Group Title	Docetaxel, Bevacizumab, and ADT
Arm/Group Description	Docetaxel: Intravenously given at 75 mg/m2 on day 1 of every 3 weeks for 4 cycles Bevacizumab: Intravenously given at (15 mg/kg) on day 1 of every 3 weeks for 8 cycles ADT or Luteinizing hormone-releasing hormone agonist (LHRH): Either subcutaneously or intramuscularly every three months for a total of 6 doses (total of 18 months) Bicalutamide: Oral Bicalutamide on day 84 once daily (after completing docetaxel, at 3 month) at dose of 50 mg for a total 15 months (4-18 months) Docetaxel Bevacizumab: ntravenously given at (15 mg/kg) on day 1 of every 3 weeks for 8 cycles ADT: Either subcutaneously or intramuscularly every three months for a total of 6 doses (total of 18 months) Bicalutamide: Starting on day 84 orally once daily until hormone therapy is completed
Measure Participants	41
Grade 3 treatment related AE	16 39%
Grade 4 treatment related AEs	5 12.2%

Adverse Events

Time Frame	Assessed each cycle throughout treatment form time of first dose and up to day 30 post-treatment, up to 2 years.
Arm/Group Title	Docetaxel, Bevacizumab, and ADT
Arm/Group Description	Docetaxel: Intravenously given at 75 mg/m2 on day 1 of every 3 weeks for 4 cycles Bevacizumab: Intravenously given at (15 mg/kg) on day 1 of every 3 weeks for 8 cycles ADT or Luteinizing hormone-releasing hormone agonist (LHRH): Either subcutaneously or intramuscularly every three months for a total of 6 doses (total of 18 months) Bicalutamide: Oral Bicalutamide on day 84 once daily (after completing docetaxel, at 3 month) at dose of 50 mg for a total 15 months (4-18 months) Docetaxel Bevacizumab: ntravenously given at (15 mg/kg) on day 1 of every 3 weeks for 8 cycles ADT: Either subcutaneously or intramuscularly every three months for a total of 6 doses (total of 18 months) Bicalutamide: Starting on day 84 orally once daily until hormone therapy is completed
All Cause Mortality
	Docetaxel, Bevacizumab, and ADT
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Docetaxel, Bevacizumab, and ADT
	Affected / at Risk (%)	# Events
Total	21/41 (51.2%)
Blood and lymphatic system disorders
Hematologic-other	1/41 (2.4%)
Thrombotic microangiopathy	1/41 (2.4%)
Febrile neutropenia	5/41 (12.2%)
Cardiac disorders
Left ventricular systolic dysfunction	1/41 (2.4%)
Gastrointestinal disorders
Lower GI= hemorrhage NOS	1/41 (2.4%)
Stomach= hemorrhage	1/41 (2.4%)
General disorders
Injection site reaction	1/41 (2.4%)
Immune system disorders
Allergic reaction	1/41 (2.4%)
Infections and infestations
Perforation= appendix	1/41 (2.4%)
Infection Gr0-2 neut= muscle	1/41 (2.4%)
Infection Gr0-2 neut= wound	1/41 (2.4%)
Investigations
Leukocytes	2/41 (4.9%)
Neutrophils	11/41 (26.8%)
Metabolism and nutrition disorders
Hyponatremia	1/41 (2.4%)
Nervous system disorders
Leukoencephalopathy	1/41 (2.4%)
Neurologic-other	1/41 (2.4%)
Renal and urinary disorders
Proteinuria	1/41 (2.4%)
Skin and subcutaneous tissue disorders
Hand-foot reaction	1/41 (2.4%)
Vascular disorders
Hypertension	4/41 (9.8%)
Other (Not Including Serious) Adverse Events
	Docetaxel, Bevacizumab, and ADT
	Affected / at Risk (%)	# Events
Total	41/41 (100%)
Blood and lymphatic system disorders
Hemoglobin	1/41 (2.4%)
Cardiac disorders
Sinus arrhythmia	1/41 (2.4%)
Endocrine disorders
Endocrine-other	1/41 (2.4%)
Eye disorders
Vision-blurred	1/41 (2.4%)
Tearing	9/41 (22%)
Gastrointestinal disorders
Constipation	4/41 (9.8%)
Diarrhea w/o prior colostomy	8/41 (19.5%)
Dry mouth	1/41 (2.4%)
Flatulence	1/41 (2.4%)
Gastritis	1/41 (2.4%)
Dyspepsia	5/41 (12.2%)
Hemorrhoids	1/41 (2.4%)
Muco/stomatitis by exam= oral cavity	6/41 (14.6%)
Muco/stomatitis (symptom) oral cavity	8/41 (19.5%)
Nausea	13/41 (31.7%)
Vomiting	2/41 (4.9%)
GI-other	1/41 (2.4%)
Anus= hemorrhage	1/41 (2.4%)
Oral cavity= hemorrhage	2/41 (4.9%)
Rectum= hemorrhage	4/41 (9.8%)
Abdomen= pain	2/41 (4.9%)
Oral cavity= pain	3/41 (7.3%)
Stomach= pain	1/41 (2.4%)
General disorders
Fatigue	35/41 (85.4%)
Fever w/o neutropenia	2/41 (4.9%)
Rigors/chills	1/41 (2.4%)
Edema limb	7/41 (17.1%)
Edema trunk/genital	1/41 (2.4%)
Pain-other	3/41 (7.3%)
Flu-like syndrome	2/41 (4.9%)
Immune system disorders
Allergic reaction	8/41 (19.5%)
Infections and infestations
Infection Gr0-2 neut= oral cavity	1/41 (2.4%)
Infection Gr0-2 neut= skin	1/41 (2.4%)
Infection w/ unk ANC dental-tooth	1/41 (2.4%)
Infection w/ unk ANC upper airway NOS	1/41 (2.4%)
Infection-other	1/41 (2.4%)
Investigations
Leukocytes	4/41 (9.8%)
Neutrophils	2/41 (4.9%)
Weight gain	3/41 (7.3%)
Weight loss	1/41 (2.4%)
Alkaline phosphatase	1/41 (2.4%)
ALT= SGPT	5/41 (12.2%)
AST= SGOT	6/41 (14.6%)
Creatinine	1/41 (2.4%)
Metabolism and nutrition disorders
Anorexia	2/41 (4.9%)
Dehydration	1/41 (2.4%)
Hyperkalemia	1/41 (2.4%)
Musculoskeletal and connective tissue disorders
Nonneuropathic generalized weakness	1/41 (2.4%)
Muscular/skeletal hypoplasia	1/41 (2.4%)
Back= pain	1/41 (2.4%)
Buttock= pain	2/41 (4.9%)
Extremity-limb= pain	3/41 (7.3%)
Joint= pain	6/41 (14.6%)
Muscle= pain	4/41 (9.8%)
Nervous system disorders
Taste disturbance	19/41 (46.3%)
Mental status	1/41 (2.4%)
Neuropathy CN V jaw / face-sensory	1/41 (2.4%)
Neuropathy-sensory	12/41 (29.3%)
Neurologic-other	1/41 (2.4%)
Head/headache	12/41 (29.3%)
Psychiatric disorders
Insomnia	5/41 (12.2%)
Depression	4/41 (9.8%)
Libido	4/41 (9.8%)
Renal and urinary disorders
Proteinuria	3/41 (7.3%)
Incontinence urinary	1/41 (2.4%)
Urinary frequency/urgency	1/41 (2.4%)
Reproductive system and breast disorders
Breast= pain	1/41 (2.4%)
Scrotum= pain	1/41 (2.4%)
Testicle= pain	1/41 (2.4%)
Erectile impotence	4/41 (9.8%)
Gynecomastia	2/41 (4.9%)
Sexual/Reproductive function-Other	1/41 (2.4%)
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	4/41 (9.8%)
Nose= hemorrhage	17/41 (41.5%)
Throat/pharynx/larynx= pain	2/41 (4.9%)
Cough	4/41 (9.8%)
Dyspnea	2/41 (4.9%)
Nasal cavity/paranasal sinus reaction	8/41 (19.5%)
Pleural effusion (non-malignant)	1/41 (2.4%)
Voice changes/dysarthria	3/41 (7.3%)
Pulmonary/Upper Respiratory-other	1/41 (2.4%)
Skin and subcutaneous tissue disorders
Sweating	2/41 (4.9%)
Dry skin	2/41 (4.9%)
Alopecia	19/41 (46.3%)
Hyperpigmentation	1/41 (2.4%)
Nail changes	11/41 (26.8%)
Rash/desquamation	2/41 (4.9%)
Rash: acne/acneiform	1/41 (2.4%)
Hand-foot reaction	1/41 (2.4%)
Skin-other	1/41 (2.4%)
Vascular disorders
Hypertension	16/41 (39%)
Flushing	1/41 (2.4%)
Hot flashes	31/41 (75.6%)
Hematoma	1/41 (2.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.