Radiation Therapy, Androgen Suppression, and Docetaxel in Treating Patients With High-Risk Prostate Cancer Who Have Undergone Radical Prostatectomy

Radiation Therapy Oncology Group80 enrolled

Overview

RATIONALE: Specialized radiation therapy that delivers a high-dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. Androgens can cause the growth of prostate cancer cells. Antihormone therapy, such as leuprolide, goserelin, flutamide, or bicalutamide, may lessen the amount of androgens made by the body. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving radiation therapy together with androgen suppression and docetaxel after surgery may kill any tumor cells that remain after surgery. PURPOSE: This phase II trial is studying how well giving radiation therapy together with androgen suppression and docetaxel works in treating patients with high risk prostate cancer who have undergone radical prostatectomy.

OBJECTIVES: Primary * To assess whether the addition of androgen suppression therapy and docetaxel to adjuvant radiotherapy improves freedom from progression. Secondary * To assess freedom from local-regional progression, distant metastases, disease-free survival, prostate cancer specific survival, non-prostate cancer specific survival, overall survival, and time to biochemical (PSA) failure. * To evaluate treatment-related "acute" and "late" toxicity based on Common Toxicity Criteria for Adverse Effects (CTCAE) v3.0. * To correlate genomic and proteomic biomarkers with the primary and secondary clinical endpoints utilizing archival prostatectomy tissue and pretreatment and prospectively collected serum/plasma. OUTLINE: This is a multicenter study. * Androgen suppression therapy: Patients receive a luteinizing hormone-releasing hormone (LHRH) agonist (leuprolide or goserelin) as an injection AND an oral antiandrogen (flutamide 3 times daily or bicalutamide once daily) for up to 6 months. * Radiotherapy: Beginning 8 weeks after the initiation of androgen suppression therapy, patients undergo 3-dimensional conformal radiotherapy or intensity-modulated radiotherapy once a day 5 days a week for up to approximately 8 weeks. * Chemotherapy: Beginning 3-6 weeks after the completion of radiotherapy, patients receive docetaxel IV over 1 hour on day 1. Treatment repeats every 21 days for up to 6 courses. After the completion of study treatment, patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

Study Type

INTERVENTIONAL

Allocation

Interventions

bicalutamideDRUG

50 mg (one tablet) daily orally for 6 months, starting within 6 months after registration

docetaxelDRUG

75 mg/m2 IV over 1 hour on day 1 of each cycle q21 days for 6 cycles, starting 3-6 weeks after completion of radiation therapy

flutamideDRUG

250 mg (two 125-mg capsules) three times daily (total 750 mg) orally for 6 months, starting within 6 months after registration

LHRH agonistDRUG

LHRH agonist (such as leuprolide, goserelin, buserelin, or triptorelin) for 6 months, starting within 6 weeks after registration

3-dimensional conformal radiation therapyRADIATION

radiation therapyRADIATION

66.6 Gy (1.8 Gy per fraction, 5 days per week) to the prostate bed (IMRT or 3DCRT), starting 8 weeks after start of hormones

Eligibility

Sex: MALEMin age: 18 Years

Medical Language ↔ Plain English

DISEASE CHARACTERISTICS: * Pathologically proven adenocarcinoma of the prostate gland meeting one of the following criteria: * Gleason ≥ 7and post-operative PSA nadir \> 0.2 ng/ml with any pathologic tumor (pT) classification * Gleason ≥ 8, post-operative PSA nadir ≤ 0.2 ng/ml and ≥ pT3a classification * Must have undergone radical prostatectomy within the past year * PSA must be obtained within 6 weeks (42 days) prior to study registration * No lymph node or distant metastases (N0, M0), based upon the following minimum diagnostic workup: * History and physical examination within 8 weeks prior to study registration * Bone scan and CT or MRI of the pelvis and no evidence of osseous metastases on bone scan within 16 weeks prior to study registration * No pelvic lymph nodes \> 1.5 cm in greatest dimension on CT scan or MRI of the pelvis within 16 weeks prior to study registration, unless the enlarged lymph node is biopsied and negative PATIENT CHARACTERISTICS: * Zubrod performance status 0-1 * Absolute neutrophil count (ANC) ≥ 2,000/mm³ * Platelet count ≥ 100,000/mm³ * Hemoglobin ≥ 8.0 g/dL (transfusion or other intervention to achieve hemoglobin ≥ 8.0 g/dL is acceptable) * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 1.5 times upper limit of normal (ULN) * Alkaline phosphatase ≤ 2.5 times ULN * Total bilirubin ≤ 1.2 times ULN * No other invasive malignancy within the past 3 years except non-melanomatous skin cancer * No active, severe co-morbidity, including any of the following: * Unstable angina and/or congestive heart failure requiring hospitalization within the past 6 months * Transmural myocardial infarction within the past 6 months * Acute bacterial or fungal infection requiring intravenous antibiotics * Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy * AIDS * HIV testing is not required for study entry * No prior allergic reaction to the study drug(s) PRIOR CONCURRENT THERAPY: * No prior systemic chemotherapy for prostate cancer * More than 3 years since prior chemotherapy for a different cancer * No prior androgen deprivation for treatment of prostate cancer * Prior use of hormonal agents, such as finasteride or dutasteride, for treatment of benign prostatic hypertrophy is allowed * No prior radiotherapy to the region of the prostate that would result in overlap of radiotherapy fields

Locations (70)

Arizona Oncology Services Foundation

Phoenix, Arizona, United States

Auburn Radiation Oncology

Auburn, California, United States

Radiation Oncology Centers - Cameron Park

Cameron Park, California, United States

Mercy Cancer Center at Mercy San Juan Medical Center

Carmichael, California, United States

Radiation Oncology Center - Roseville

Roseville, California, United States

Outcomes

Primary Outcomes

Number of Participants Free From Progression at 3 Years

Failure was defined as PSA ≥ 0.4 ng/mL after the end of radiation therapy confirmed by a second higher PSA, non-protocol hormones, local-regional progression, distant metastasis, or death, within 3 years after study registration. Freedom from progression (FFP) rate under null hypothesis was 50%; under alternative hypothesis ≥ 70%. Per Fleming's multiple testing procedure with 3 stages, 69 patients (76 allowing for 10% ineligible) were required for 90% power and type I error 0.025. If ≥ 44 of 69 patients had a FFP event, we would reject 50% FFP rate in favor of ≥ 70%. Analysis was out of 74 patients (not 69), so ≥ 44 was revised to ≥ 46.

Time frame: From registration to 3 years.

Secondary Outcomes

Local-regional Progression (3 Year Rate)

Time from registration to date of local progression (failure), death (competing risk), or last follow-up (censored). Three-year failure rate and 95% confidence interval were estimated by the cumulative incidence method.