TREATMENT OF EARLY RECURRENT PROSTATE-CANCER WITH 1,25-DIHYDROXYVITAMIN-D3 (CALCITRIOL)

Purpose: Substantial experimental and epidemiological data indicate th at 1,25-dihydroxyvitamin D3 (calcitriol) has potent antiproliferative effects on human prostate cancer cells. We performed an open label, no nrandomized pilot trial to determine whether calcitriol therapy is saf e and efficacious for early recurrent prostate cancer. Our hypothesis was that calcitriol therapy slows the rate of rise of prostate specifi c antigen (PSA) compared with the pretreatment rate. Materials and Met hods: After primary treatment with radiation or surgery recurrence was indicated by rising serum PSA levels documented on at least 3 occasio ns. Seven subjects completed 6 to 15 months of calcitriol therapy, sta rting with 0.5 mu g. calcitriol daily and slowly increasing to a maxim um dose of 2.5 mu g. daily depending on individual calciuric and calce mic responses. Each subject served as his own control, comparing the r ate of PSA rise before and after calcitriol treatment. Results: As det ermined by multiple regression analysis, the rate of PSA rise during v ersus before calcitriol therapy significantly decreased in 6 of 7 pati ents, while in the remaining man a deceleration in the rate of PSA ris e did not reach statistical significance. Overall the decreased rate o f PSA rise was statistically significant (p = 0.02 Wilcoxon signed ran k test). Dose dependent hypercalciuria limited the maximal calcitriol therapy given (range 1.5 to 2.5 mu g. daily). Conclusions: This pilot study provides preliminary evidence that calcitriol effectively slows the rate of PSA rise in select cases, although dose dependent calciuri c side effects limit its clinical usefulness. The development of calci triol analogues with decreased calcemic side effects is promising, sin ce such analogues may be even more effective for treating prostate can cer.