Intermittent androgen suppression in the LuCaP 23.12 prostate cancer xenograft model

BACKGROUND. Intermittent androgen suppression (IAS) has been proposed as a method of delaying the onset of androgen-independent growth in prostate can cer. While several pilot studies have demonstrated the feasibility of such a treatment, no study to date has defined the effect of IAS on survival. METHODS. We developed an IAS protocol for mice bearing the LuCaP 23.12 huma n prostate cancer xenograft, with each cycle consisting of 1 week of androg en replacement with a testosterone pellet followed by 3 weeks of androgen w ithdrawal. Mice that responded to castration with a 40% or greater decrease in serum prostate-specific antigen (PSA) were randomized to treatment with either continuous androgen suppression (CAS) or IAS. Serum PSA, tumor volu me, and overall survival were monitored. RESULTS. A total of 75 mice met the randomization criteria. There was no si gnificant difference of survival between animals heated with CAS or IAS (18 5 vs. 239 days, P = 0.1835). Serum PSA showed evidence of cycling with horm onal manipulation. No cycling was noted in tumor volume. CONCLUSIONS. IAS is not associated with a decrease in survival compared to CAS, yet in patients may offer quality-of-life improvements. Further studie s of IAS in the setting of Institutional Review Board (IRB) approved clinic al trials should be encouraged. Prostate 43: 63-70, 2000. Published 2000 Wi ley-Liss, Inc.(+)