Prostate Cancer
Conditions
Keywords
adenocarcinoma of the prostate, stage IV prostate cancer, recurrent prostate cancer
Brief summary
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Androgens can stimulate the growth of prostate cancer cells. Drugs such as goserelin, leuprolide, flutamide, or bicalutamide may stop the adrenal glands from producing androgens. Combining chemotherapy with hormone therapy may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy plus hormone therapy in treating patients who have metastatic prostate cancer.
Detailed description
OBJECTIVES: * Determine the progression-free and overall survival in patients with high-risk metastatic adenocarcinoma of the prostate treated with early estramustine, etoposide, and paclitaxel with combined androgen-blockade therapy. * Determine the type, frequency, and severity of toxicity of this regimen in this patient population. OUTLINE: This is a multicenter study. * Androgen-blockade therapy: Patients receive a standard regimen of luteinizing hormone-releasing hormone agonist therapy comprising either goserelin subcutaneously once monthly or once every 3 months or leuprolide intramuscularly once monthly, once every 3 months, or once every 4 months. Patients also receive a standard regimen of antiandrogen therapy comprising oral bicalutamide, oral flutamide, or oral nilutamide once daily. Treatment continues in the absence of disease progression or unacceptable toxicity. * Chemotherapy: Beginning 14-30 days after initiation of androgen-blockade therapy, patients receive oral estramustine three times daily and oral etoposide once daily on days 1-14 and paclitaxel IV over 1 hour on day 2. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months until disease progression, every 6 months for 2 years, and then annually for 3 years. PROJECTED ACCRUAL: A total of 80 patients will be accrued for this study within 2 years.
Interventions
DRUGbicalutamide
DRUGestramustine
DRUGetoposide
DRUGflutamide
DRUGgoserelin
DRUGleuprolide
DRUGnilutamide
DRUGpaclitaxel
Sponsors
National Cancer Institute (NCI)
SWOG Cancer Research Network
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically or cytologically confirmed high-risk adenocarcinoma of the prostate * Clinical stage D2 disease as evidenced by one of the following: * Visceral disease (liver, lung, or other viscera) * Bone metastases to sites in both the axial (spine, pelvis, ribs, or skull) and appendicular (claviculae, humeri, or femora) skeleton * No prior or concurrent (treated or untreated) brain metastases * Patients with clinical evidence of brain metastasis must have a negative brain CT or MRI * No evidence of untreated spinal cord compression PATIENT CHARACTERISTICS: Age: * Over 18 Performance status: * Zubrod 0-2 Life expectancy: * Not specified Hematopoietic: * Absolute granulocyte count at least 1,500/mm\^3 * Platelet count at least 100,000/mm\^3 * No active hypercoagulability Hepatic: * Not specified Renal: * Not specified Cardiovascular: * No transient ischemic attacks, stroke, or myocardial infarction within the past 6 months * No active coronary artery disease requiring antianginal therapy * No active thrombophlebitis Pulmonary: * No history of pulmonary embolus Other: * No other prior malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or adequately treated stage I or II cancer currently in complete remission PRIOR CONCURRENT THERAPY: Biologic therapy: * At least 4 weeks since prior biologic therapy and recovered * No concurrent biologic therapy Chemotherapy: * No prior cytotoxic chemotherapy * No other concurrent chemotherapy Endocrine therapy: * Prior androgen-blockade therapy (e.g., luteinizing hormone-releasing hormone agonist and antiandrogen therapy) allowed if administered for a duration of less than 30 days * Prior neoadjuvant hormonal therapy allowed Radiotherapy: * At least 4 weeks since prior radiotherapy and recovered * No concurrent radiotherapy Surgery: * At least 4 weeks since prior surgery and recovered Other: * No concurrent bisphosphonates
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | 0-5 years | Overall survival is defined from the date of registration to date of death from any cause |
| Progression-free Survival | 0-5 years (assessed every 3 months if no progression when the chemotherapy had been finished. Once off chemotherapy, assessed every 3 months until progression) | Measured from time of registration to time of first documentation of progression determined from the prostate-specific antigen (PSA) level, clinical criteria, or symptomatic deterioration. PSA progression is defined as a 25% increase greater than baseline. If the patient's PSA level had decrease during the study, a 25% increase from the nadir PSA level, with absolute value of \>=5 ng/mL is considered progression. CLinical progress is defined as the appearance of any new lesion at any site or death without documented progression. Symptomatic deterioration is defined as a global deterioration of the health status requiring discontinuation of treatment without objective evidence of progression. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | up to 5 years after registration | Adverse Events (AEs) are reported by the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 2.0. For each patient, worst grade of each event type is reported. Grade 3 = Severe, Grade 4 = Life-threatening, Grade 5 = Fatal. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| CAD + Chemo Patients receive Combined androgen deprivation (CAD) therapy with LHRH agonist (goserelin acetate or leuprolide acetate) sq/IM q 1-4 months depending on dose chosen by the treating physician and oral antiandrogen (250 mg/tid of flutamide, 50 mg/d of bicalutamide or 300 mg/d for 30 days then 150 mg/d of nilutamide) given continuously until disease progression and Chemotherapy (4 cycles of estramustine 280 mg orally 3 times daily and etoposide 50 mg/m\^2 daily for 14 days of each 21-day cycle, with paclitaxel 135 mg/m\^2 given intravenously within 1 hour on day 2 of each cycle) | 35 |
| Total | 35 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Ineligible | 5 |
| Overall Study | Not Analyzable | 1 |
| Overall Study | Other - Not Protocol Specified | 1 |
| Overall Study | Progression or Death | 31 |
| Overall Study | Refusal Unrelated to Adverse Events | 1 |
Baseline characteristics
| Characteristic | CAD + Chemo |
|---|---|
| Age Continuous | 60 years |
| Bone Pain Grade (CTC version 2.0) <2 | 26 participants |
| Bone Pain Grade (CTC version 2.0) >=2 | 7 participants |
| Bone Pain Grade (CTC version 2.0) Missing | 2 participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 32 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Gleason Score 6 | 2 participants |
| Gleason Score 7 | 12 participants |
| Gleason Score 8 | 6 participants |
| Gleason Score 9-10 | 14 participants |
| Gleason Score Missing | 1 participants |
| Previous Prostatectomy No/Unknown | 29 participants |
| Previous Prostatectomy Yes | 6 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 9 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 26 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 35 Participants |
| Southwestern Oncology Group Performance Status 0 | 20 participants |
| Southwestern Oncology Group Performance Status 1 | 15 participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 35 / 35 |
| serious Total, serious adverse events | 6 / 35 |
Outcome results
Primary
Overall Survival (OS)
Overall survival is defined from the date of registration to date of death from any cause
Time frame: 0-5 years
Population: All eligible patients who started treatment were included in the analysis
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| CAD + Chemo | Overall Survival (OS) | 38 months |
Primary
Progression-free Survival
Measured from time of registration to time of first documentation of progression determined from the prostate-specific antigen (PSA) level, clinical criteria, or symptomatic deterioration. PSA progression is defined as a 25% increase greater than baseline. If the patient's PSA level had decrease during the study, a 25% increase from the nadir PSA level, with absolute value of \>=5 ng/mL is considered progression. CLinical progress is defined as the appearance of any new lesion at any site or death without documented progression. Symptomatic deterioration is defined as a global deterioration of the health status requiring discontinuation of treatment without objective evidence of progression.
Time frame: 0-5 years (assessed every 3 months if no progression when the chemotherapy had been finished. Once off chemotherapy, assessed every 3 months until progression)
Population: All eligible patients who started treatment were included in the analysis
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| CAD + Chemo | Progression-free Survival | 13 months |
Secondary
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug
Adverse Events (AEs) are reported by the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 2.0. For each patient, worst grade of each event type is reported. Grade 3 = Severe, Grade 4 = Life-threatening, Grade 5 = Fatal.
Time frame: up to 5 years after registration
Population: Eligible patients who had received any treatment were included in the adverse event summaries. Any CTCAE 2.0 event of Grade 3 (severe), Grade 4 (life threatening), or Grade 5 (fatal) which deemed to be related to protocol treatment are included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CAD + Chemo | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Infection with 3-4 neutropenia | 2 Participants |
| CAD + Chemo | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Alkaline phosphatase increase | 1 Participants |
| CAD + Chemo | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Anemia | 1 Participants |
| CAD + Chemo | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Bilirubin increase | 1 Participants |
| CAD + Chemo | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Cardiac ischemia/infarction | 1 Participants |
| CAD + Chemo | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Confusion | 1 Participants |
| CAD + Chemo | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Constipation/bowel obstruction | 1 Participants |
| CAD + Chemo | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Edema | 2 Participants |
| CAD + Chemo | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Erectile impotence | 3 Participants |
| CAD + Chemo | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Fatigue/malaise/lethargy | 2 Participants |
| CAD + Chemo | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | GI-other | 1 Participants |
| CAD + Chemo | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Hyperglycemia | 2 Participants |
| CAD + Chemo | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Infection w/o 3-4 neutropenia | 1 Participants |
| CAD + Chemo | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Leukopenia | 9 Participants |
| CAD + Chemo | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Lymphopenia | 2 Participants |
| CAD + Chemo | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Neutropenia/granulocytopenia | 9 Participants |
| CAD + Chemo | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | PRBC transfusion | 2 Participants |
| CAD + Chemo | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Pain-other | 1 Participants |
| CAD + Chemo | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Prothrombin time increase | 1 Participants |
| CAD + Chemo | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Renal failure | 1 Participants |
| CAD + Chemo | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Second primary | 1 Participants |
| CAD + Chemo | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Thrombocytopenia | 1 Participants |
| CAD + Chemo | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Thrombosis/embolism | 4 Participants |