Prostate Cancer
Conditions
Keywords
adenocarcinoma of the prostate, stage III 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 or leuprolide may stop the adrenal glands from producing androgens. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining chemotherapy, hormone therapy, and radiation therapy may kill more tumor cells. PURPOSE: This phase II trial is studying giving chemotherapy together with hormone therapy and radiation therapy in treating patients with locally advanced prostate cancer.
Detailed description
OBJECTIVES: * Determine the feasibility and safety of paclitaxel, estramustine, carboplatin, and androgen ablation followed by radiotherapy in patients with poor-prognosis locally advanced prostate cancer. * Determine the progression-free survival and time to prostate specific antigen failure in patients treated with this regimen. OUTLINE: This is a multicenter study. Patients receive paclitaxel IV over 1 hour once weekly; oral estramustine three times a day, five days a week; and carboplatin IV over 1 hour once monthly. Treatment repeats every 4 weeks for 4 courses. Patients also receive gonadotropin-releasing hormonal therapy comprising either goserelin subcutaneously or leuprolide intramuscularly once monthly. Treatment repeats every 4 weeks for 6 courses. After the completion of chemotherapy, patients undergo radiotherapy once daily on weeks 17-24. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months for 2 years and then every 6 months for 4 years. PROJECTED ACCRUAL: A total of 60 patients will be accrued for this study within 1.5 years.
Interventions
RADIATIONradiation therapy
77.4 Gy in 1.8 Gy fractions
DRUGleuprolide or goserelin acetate
7.5 mg IM injection once every 4 weeks for 6 months
DRUGcarboplatin
AUC=6 week one of each 4 week cycle
DRUGestramustine
2 tablets tid PO 5 of 7 days per week each 4 week cycle
DRUGpaclitaxel
80 mg/sq m IV infusion over 1 hour weekly for ea 4 week cycle
Sponsors
National Cancer Institute (NCI)
Alliance for Clinical Trials in Oncology
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 confirmed adenocarcinoma of the prostate with one of the following prognostic factors: * Tx N0, baseline prostate specific antigen (PSA) greater than 20 ng/mL, and Gleason score at least 7 * T3b-4 N0, any baseline PSA, and any Gleason score * No pelvic lymph node disease requiring pelvic radiotherapy * No metastatic disease by bone scan, CT scan, or MRI PATIENT CHARACTERISTICS: Age: * 18 and over Performance status: * ECOG 0-2 Life expectancy: * Not specified Hematopoietic: * Granulocyte count at least 1,500/mm\^3 * Platelet count at least 100,000/mm\^3 Hepatic: * Bilirubin no greater than 1.5 times upper limit of normal (ULN) * SGOT no greater than 1.5 times ULN Renal: * Creatinine no greater than 1.5 times ULN Cardiovascular: * No significant cardiovascular disease * No New York Heart Association class III or IV congestive heart failure * No active angina pectoris * No myocardial infarction within the past 6 months * No history of hemorrhagic or thrombotic cerebral vascular accident * No deep vein thrombosis within the past 6 months Pulmonary: * No pulmonary embolism within the past 6 months Other: * Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy: * No prior immunotherapy for prostate cancer * No concurrent routine filgrastim (G-CSF) or sargramostim (GM-CSF) Chemotherapy: * No prior chemotherapy for prostate cancer * No other concurrent anticancer chemotherapy Endocrine therapy: * No more than 6 weeks of prior androgen deprivation therapy * No other concurrent anticancer hormonal therapy except steroids for adrenal failure and/or hormones for nondisease-related conditions (e.g., insulin for diabetes) Radiotherapy: * See Disease Characteristics * No prior radiotherapy for prostate cancer * No other concurrent anticancer radiotherapy Surgery: * At least 4 weeks since prior major surgery Other: * No prior alternative therapy (e.g., PC-SPES) for prostate cancer * No concurrent alternative medicine (e.g., PC-SPES or saw palmetto) or large quantities of vitamins * No other concurrent anticancer therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Toxicity | 90 days and 1 year post treatment | Patients were evaluated for acute toxicities defined as grade 3 or greater cardiovascular (including venous thrombosis), gastrointestinal, or genitourinary toxicity occurring during the period starting from treatment initiation until 90 days or less after the completion of radiotherapy. The same toxicity measures were monitored at \>90 days after the completion of radiotherapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Prostate-specific Antigen Failure | PSA was measured every 4 weeks during chemotherapy, at least every 12 weeks post radiation for 2 years, and every 6 months thereafter until PSA failure date (Up to 5.5 years). | PSA progression was defined in 2 ways. The CALGB PSA progression was defined as 2 consecutive rises in PSA with a rise of at least 0.2 ng/mL and above 1.0 ng/mL after radiation therapy; the date of PSA failure is taken as the midpoint between the last PSA before the rise and the first of the 2 PSAs that documented the rise. In addition, PSA progression was used according to the American Society for Therapeutic Radiology and Oncology 1996 (ASTRO) criteria and defined as 3 consecutive rises in PSA after radiation therapy. The date of PSA failure was taken as the midpoint between the time of the lowest PSA measure after irradiation and the first of the 3 consecutive rises. |
| Progression-free Survival (PFS) | registration to progression, up to 5.5 years from registration | PFS was defined as the time between treatment initiation and the date of disease progression (PSA, bone, tumor) or death, whichever occurred first. PSA progression is defined as 2 consecutive rising PSAs (a rise of at least 0.2 ng/mL) above 1.0 ng/mL. |
Countries
United States
Participant flow
Recruitment details
Between May 15, 2001 and June 30, 2006, a total of 34 patients were enrolled in the study. All CALGB institutions, comprised of 29 major university medical centers and their affiliates, were approved to participate in this study, of which 10 CALGB sites enrolled patients.
Pre-assignment details
Of these 34 patients, 4 patients did not have radiotherapy, 2 patients were ineligible, and 1 case had limited follow-up data after radiotherapy. Final analyses were performed on 27 patients.
Participants by arm
| Arm | Count |
|---|---|
| Neo-Adj ChemoTx + Ablation Prior to RT Treatment with chemotherapy plus androgen ablation prior to radiation treatment for poor prognosis localized prostate cancer | 27 |
| Total | 27 |
Baseline characteristics
| Characteristic | Neo-Adj ChemoTx + Ablation Prior to RT |
|---|---|
| Age, Continuous | 61 years |
| Region of Enrollment United States | 27 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 29 / 29 |
| serious Total, serious adverse events | 0 / 29 |
Outcome results
Primary
Toxicity
Patients were evaluated for acute toxicities defined as grade 3 or greater cardiovascular (including venous thrombosis), gastrointestinal, or genitourinary toxicity occurring during the period starting from treatment initiation until 90 days or less after the completion of radiotherapy. The same toxicity measures were monitored at \>90 days after the completion of radiotherapy.
Time frame: 90 days and 1 year post treatment
Population: Final analyses were performed on all 27 eligible patients.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Neo-Adj ChemoTx + Ablation Prior to RT | Toxicity | Grade 3+ Toxicity <=90 days post radiotherapy | 2 Events |
| Neo-Adj ChemoTx + Ablation Prior to RT | Toxicity | Grade 3+ Toxicity >90 days post radiotherapy | 0 Events |
Secondary
Progression-free Survival (PFS)
PFS was defined as the time between treatment initiation and the date of disease progression (PSA, bone, tumor) or death, whichever occurred first. PSA progression is defined as 2 consecutive rising PSAs (a rise of at least 0.2 ng/mL) above 1.0 ng/mL.
Time frame: registration to progression, up to 5.5 years from registration
Population: All 27 evaluable patients were used in this analysis
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Neo-Adj ChemoTx + Ablation Prior to RT | Progression-free Survival (PFS) | 12.1 months |
Secondary
Time to Prostate-specific Antigen Failure
PSA progression was defined in 2 ways. The CALGB PSA progression was defined as 2 consecutive rises in PSA with a rise of at least 0.2 ng/mL and above 1.0 ng/mL after radiation therapy; the date of PSA failure is taken as the midpoint between the last PSA before the rise and the first of the 2 PSAs that documented the rise. In addition, PSA progression was used according to the American Society for Therapeutic Radiology and Oncology 1996 (ASTRO) criteria and defined as 3 consecutive rises in PSA after radiation therapy. The date of PSA failure was taken as the midpoint between the time of the lowest PSA measure after irradiation and the first of the 3 consecutive rises.
Time frame: PSA was measured every 4 weeks during chemotherapy, at least every 12 weeks post radiation for 2 years, and every 6 months thereafter until PSA failure date (Up to 5.5 years).
Population: All 27 evaluable patients were used in this analysis.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Neo-Adj ChemoTx + Ablation Prior to RT | Time to Prostate-specific Antigen Failure | CALGB criteria | 17.1 months |
| Neo-Adj ChemoTx + Ablation Prior to RT | Time to Prostate-specific Antigen Failure | ASTRO criteria | 12.1 months |