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The Oncologist, Vol. 5, No. 1, 45-52, February 2000
© 2000 AlphaMed Press

Intermittent Androgen Deprivation in Prostate Cancer Patients: Factors Predictive of Prolonged Time Off Therapy

Stephen B. Strum, Mark C. Scholz, Jonathan E. McDermed

The Prostate Cancer Research Institute, Los Angeles, California, USA

Correspondence: Stephen B. Strum, MD, 4676 Admiralty Way, Suite #101, Marina del Rey, CA 90292, USA. Telephone: 310-827-7707; Fax: 310-574-4002; e-mail: sbstrum{at}mediaone.net

Objectives. We hypothesize that prostate cancer (PC) patients who achieve and maintain an undetectable prostate-specific antigen (UD-PSA) on androgen deprivation therapy (ADT) have a predominantly androgen-dependent cancer cell population sensitive to apoptosis that allows for a prolonged time off ADT. This study summarizes patient- and treatment-related factors associated with a prolonged time off ADT in patients electing intermittent androgen deprivation (IAD).

Methods. Hormone-naïve patients with PC were treated with ADT using an antiandrogen and a luteinizing-hormone-releasing hormone-agonist. Of 255 consecutive patients, 216 (85%) achieved a UD-PSA (<0.05 ng/ml). Ninety-three (43%) of 216 elected to stop ADT after maintaining a UD-PSA for a median of one year. Patients were followed off therapy and advised to restart ADT if the PSA level reached >=5.0 ng/ml. Forty-one patients received finasteride as part of IAD induction and as maintenance off therapy; these patients are excluded from the current study and are the focus of another publication. The remaining 52 patients are assessable for response being either in the off-phase of IAD >=1 year or having restarted IAD.

Results. In the first IAD cycle, the median duration of the on-phase of IAD was 16 months (mean 19.0 months, range 3.6-71 months), and the median off-phase duration was 15.5 months (mean 24.1 months, range 3.2-87+ months). In 28 patients who maintained a UD-PSA for >=1 year, their median off-phase duration was 29 months (mean 35.8 months, range 7.8-87+ months), with nine (32%) still off IAD after a median follow-up of 62 months. Significant (p < 0.05) independent factors associated with prolonged off-phase duration by multivariate analysis included UD-PSA on ADT >=1 year (p = 0.010), PSA-only recurrence after local therapy (p = 0.039), and reaching a testosterone level >=150 ng/dl in >=4 months off ADT (p = 0.041). After a median of 66 months of follow-up, only one (2%) patient developed androgen-independent PC.

Conclusions. Hormone-naïve patients who achieve and maintain a UD-PSA for at least one year during ADT may initiate IAD and anticipate a prolonged off-phase duration. Attainment of a UD-PSA on ADT may serve as an in vivo sensitivity test of a patient's tumor cell population, and allow for better selection of those best suited for IAD.

Key Words. Prostate cancer • Androgen-deprivation • Intermittent hormone therapy




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