Hormone Therapy With or Without Surgery or Radiation Therapy in Treating Patients With Prostate Cancer

NCIC Clinical Trials Group

Status and phase: Completed; Phase 3

Conditions: Prostate Cancer

Treatments: Radiation: radiation therapy; Drug: nilutamide; Drug: flutamide; Drug: goserelin; Drug: buserelin; Procedure: orchiectomy; Drug: bicalutamide; Drug: leuprolide acetate

Study type: Interventional

Funder types: Other; NETWORK; NIH

Identifiers

NCT00002633

ECOG-JPR03 (Other Identifier)

CDR0000064065 (Other Identifier)

MRC-PR07 (Other Identifier)

SWOG-JPR3 (Other Identifier)

PR3

NCI-T94-0110O (Other Grant/Funding Number)

EU-99013 (Other Identifier)

ISRCTN24991896 (Registry Identifier)

CAN-NCIC-PR3 (Registry Identifier)

Details and patient eligibility

About

RATIONALE: Hormones can stimulate the growth of prostate cancer cells. Hormone therapy may fight prostate cancer by reducing the production of androgens. Radiation therapy uses high-energy x-rays to damage tumor cells. It is not yet known whether hormone therapy plus surgery is more effective than hormone therapy plus radiation therapy for prostate cancer.

PURPOSE: This randomized phase III trial is studying giving hormone therapy alone to see how well it works compared to giving hormone therapy together with bilateral orchiectomy or radiation therapy in treating patients with stage III or stage IV prostate cancer.

Full description

OBJECTIVES:

• Compare the overall survival, disease specific survival, and time to progression in patients with locally advanced adenocarcinoma of the prostate treated with total androgen suppression with or without pelvic irradiation.
• Compare the symptomatic control as measured by the rates of surgical interventions needed for control of local disease (e.g., transurethral resections, stent insertions, nephrostomies, and colostomies) in patients treated with these regimens.
• Compare the quality of life of patients treated with these regimens.
• Compare the sensitivity of the EORTC-QLQ-C30+3 and a trial-specific checklist (PR17) with the FACT-P questionnaire in measuring changes in quality of life of patients treated with these regimens.

OUTLINE: This a randomized, multicenter study. Patients are stratified according to center, initial PSA level (less than 20 vs 20-50 vs greater than 50 ng/mL), method of node staging (clinical [no CT scan] vs radiological [CT scan negative] vs surgical), Gleason score (less than 8 vs 8-10), prior hormonal therapy (excluding orchiectomy) (yes vs no), and choice of hormonal therapy (bilateral orchiectomy with or without antiandrogen vs luteinizing hormone-releasing hormone [LHRH] with antiandrogen). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive antiandrogen therapy comprising oral flutamide every 8 hours, oral nilutamide every 8 hours for 1 month and then once daily, or oral bicalutamide once daily. Patients also choose to undergo bilateral orchiectomy or LHRH agonist therapy comprising goserelin subcutaneously (SC) every 4 weeks (short-acting formulation) or every 3 months (long-acting formulation), leuprolide intramuscularly every 4 weeks (short-acting formulation) or every 3 months (long-acting formulation), or buserelin SC every 8 weeks or every 12 weeks. Patients choosing orchiectomy may receive an antiandrogen for at least 6 weeks before surgery to counter any flare phenomenon and may continue the antiandrogen after surgery (at the physician's discretion).
• Arm II: Patients undergo total androgen ablation as in arm I. Patients with node-negative dissection undergo radiotherapy 5 days a week for 6.5-7 weeks. All other patients undergo radiotherapy 5 days a week for 5 weeks, followed by boost radiotherapy 5 days a week for 2-2.4 weeks.

Hormonal therapy on both arms continues in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline, on the last day of radiotherapy, at 6 months, and then every 6 months thereafter.

Patients are followed at 1, 2, and 6 months and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 1,200 patients will be accrued for this study within 7.5 years.

Enrollment: 361 patients

Sex: Male

Ages: Under 79 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically proven locally advanced adenocarcinoma of the prostate, defined as 1 of the following:

  • T3-4, N0 or NX, M0
  • T2, PSA greater than 40 µg/L
  • T2, PSA greater than 20 µg/L AND Gleason score at least 8

• Diagnosis made within the past 6 months

• Gleason score and PSA known

• Pelvic lymph nodes must be clinically negative

  • Lymph nodes no more than 1.5 cm in greatest diameter by CT scan or MRI of the pelvis
  • Negative needle aspirate required for any lymph node more than 1.5 cm
  • If a lymph node dissection was performed, it must be histologically negative

• No small cell or transitional cell carcinoma by biopsy

• No bony metastases by bone scan

PATIENT CHARACTERISTICS:

Age:

• Under 80

Performance status:

• ECOG 0-2

Life expectancy:

• At least 5 years excluding malignancy

Hematopoietic:

• Hemoglobin at least 10.0 g/dL
• WBC at least 2,000/mm^3
• Platelet count at least 100,000/mm^3

Hepatic:

• Bilirubin less than 2 times upper limit of normal (ULN)
• SGOT and SGPT less than 2 times ULN
• Alkaline phosphatase less than 2 times ULN
• No history of chronic liver disease

Renal:

• Creatinine less than 2 times ULN

Other:

• No contraindication to wide-field pelvic irradiation (e.g., inflammatory bowel disease or severe bladder irritability)
• No other malignancy within the past 5 years except nonmelanoma skin cancer
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• Not specified

Endocrine therapy:

• Prior hormonal therapy within the past 12 weeks allowed provided the following conditions are met:

  • Negative bone scan before beginning any hormonal therapy
  • Extracapsular extension remains palpable on rectal re-exam
  • Baseline PSA known before beginning any hormonal therapy

• At least 4-6 weeks since prior 5-alpha-reductase inhibitor (e.g., finasteride) for benign prostatic hypertrophy

Radiotherapy:

• No prior pelvic irradiation

Surgery:

• No prior radical prostatectomy
• Prior transurethral resection of the prostate allowed

Other:

• No prior cytotoxic anticancer therapy
• No other prior treatment for prostate cancer
• No other concurrent anticancer therapy unless documented disease progression

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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361 participants in 2 patient groups

Total Androgen Blockade

Active Comparator group

Treatment:

Drug: leuprolide acetate

Drug: bicalutamide

Drug: nilutamide

Drug: flutamide

Procedure: orchiectomy

Drug: goserelin

Drug: buserelin

Total Androgen Blockade Vs TA Blockade Plus Pelvic Irradiation

Active Comparator group

Treatment:

Drug: leuprolide acetate

Drug: bicalutamide

Radiation: radiation therapy

Drug: nilutamide

Drug: flutamide

Procedure: orchiectomy

Drug: goserelin

Drug: buserelin