Chemotherapy, Hormone Therapy, and Radiation Therapy in Treating Patients With Locally Advanced Prostate Cancer

Study Overview
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Brief Summary
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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
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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.

Official Title
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Phase II Study Of Neo-Adjuvant Paclitaxel, Estramustine And Carboplatin (TEC) Plus Androgen Ablation Prior To Radiation Therapy In Patients With Poor Prognosis Localized Prostate Cancer

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: carboplatin
* Drug: estramustine
* Drug: paclitaxel
* Radiation: radiation therapy
* Drug: leuprolide or goserelin acetate


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Neo-Adj ChemoTx + ablation prior to RT<br>Patients with localized high-risk prostate cancer were treated with 4 cycles (16 weeks) of continuous weekly paclitaxel at 80 mg/m^2 intravenously with estramustine at 280 mg orally 3 times a day for 5 days a week and carboplatin (area under the curve of 6) on Day 1 of every cycle followed by 3-dimensional conformal or intensity-modulated radiotherapy (total dose of 77.4 gray [Gy] in 1.8-Gy fractions). All patients received androgen deprivation therapy with either goserelin acetate at 3.6 mg subcutaneously or leuprolide acetate at 7.5 mg intramuscularly monthly for 6 months starting at Day 1 of therapy. | Drug: carboplatin<br>* AUC=6 week one of each 4 week cycle<br>Drug: estramustine<br>* 2 tablets tid PO 5 of 7 days per week each 4 week cycle<br>Drug: paclitaxel<br>* 80 mg/sq m IV infusion over 1 hour weekly for ea 4 week cycle<br>Radiation: radiation therapy<br>* 77.4 Gy in 1.8 Gy fractions<br>Drug: leuprolide or goserelin acetate<br>* 7.5 mg IM injection once every 4 weeks for 6 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 90 days and 1 year post treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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). | 
| 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. | registration to progression, up to 5.5 years from registration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adenocarcinoma of the prostate, stage III prostate cancer