Long term efficacy of peripheral androgen blockade on prostate cancer: CALGB 9782.

4573 Background: The treatment of patients with a rising PSA after definitive local therapy is controversial. Patients are reluctant to undergo androgen suppression due to side effects and interest focuses on the timing and intensity of additional therapy. The use of peripheral androgen blockade in this setting is appealing. METHODS: Patients with a rising PSA after definitive local therapy were enrolled in a multi-institutional trial. Accrual of 101 patients lasted from Sept 30, 1998 to July 16, 2001. All patients had undergone previous definitive local therapy at least 1 year, and no more than 10 years prior to enrollment. All patients had a repeated rising PSA, above 1 ng/ml, with no detectable evidence of recurrent disease. CT and bone scans were negative. Patients received a combination of oral therapy consisting of Finasteride, at a dose of 5 mg/day, and Flutamide, at a dose of 250 mg TID. RESULTS: The median age was 71, with a median baseline testosterone level of 322 ng/dl. A >80% PSA decline was seen in 91/94, (97%) of the patients. Three other patients had PSA declines of 77%, 73% and 38%, all of which were maintained for at least 28 days. The median time to PSA nadir was 3.2 months. The current median follow-up is 59 months. To date, only 22 patients have progressed, with 47 patients still on peripheral androgen blockade. Eight patients have died without progression, and 22 patients went off therapy for other reasons not related to progression. Also noted were patients showing PSA responses to Flutamide withdrawal, and per protocol remaining on Finasteride. Toxicity to date remains very mild. CONCLUSIONS: Peripheral androgen blockade showed excellent activity produced durable PSA responses in this select group of patients. While the clinical significance of a decline in PSA alone is not fully understood_the durability of these PSA responses is encouraging. The median duration of progression free survival and overall survival has not been reached, and is likely to be longer than five years. Quality of life data is undergoing further analysis. This report supports further study of less aggressive treatments for patients who have only a rising PSA after definitive local therapy. No significant financial relationships to disclose.

Duke Scholars

Author Susan Halabi Biostatistics & Bioinformatics, Division of Biostatistics