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

Alliance for Clinical Trials in Oncology

Status and phase: Completed; Phase 2

Conditions: Prostate Cancer

Treatments: Drug: estramustine; Drug: leuprolide or goserelin acetate; Drug: carboplatin; Radiation: radiation therapy; Drug: paclitaxel

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00016913

U10CA031946 (U.S. NIH Grant/Contract)

CALGB-99811

CDR0000068632 (Registry Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 34 patients

Sex: Male

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

---

34 participants in 1 patient group

Neo-Adj ChemoTx + ablation prior to RT

Experimental group

Description:

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.

Treatment:

Drug: carboplatin

Drug: estramustine

Drug: leuprolide or goserelin acetate

Radiation: radiation therapy

Drug: paclitaxel