A phase II trial of calcitrol and naproxen in recurrent prostate cancer

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16103 Background: Although commonly used as second-line treatment for patients with progressing prostate cancer, hormonal therapy is associated with unpleasant side effects, and has not unequivocally been shown to prolong survival. To this date, in vitro and in vivo studies, as well as early phase clinical trials, have shown a promising role for both calcitriol and nonsteroidal anti-inflammatory drugs (NSAIDs) in the treatment of prostate cancer. Because calcitriol and NSAIDs interfere with PG pathways by different mechanisms, there is reason to believe that their combined effects to inhibit PG action may be synergistic and this was in fact demonstrated in cultured human prostate cancer cells. We combined calcitriol and naproxen (a non-selective NSAID) to delay the growth and progression of early recurrent prostate cancer. Methods: Patients with biochemical relapse after local therapy for prostate cancer were treated with a very large dose of calcitriol (DN101) (45 micrograms/once per week) and naproxen (400 mg bid) for one year. Patients were followed with serum PSA levels as well as imaging studies. Progressive disease was defined as a decrease in PSA doubling time (PSADT) from baseline, or initiation of hormonal therapy, and/or formation of new bone lesions on bone scan. Results: Twenty-one patients were enrolled in the trial from 4/05–10/07. Sixteen had radical prostatectomy as primary therapy and 12 of these had subsequent radiation for a rising serum PSA. Median Gleasons score was 7, and median number of cycles of therapy was 6. Eighteen patients were evaluable for response. Four patients met criteria for progression, with a PSADT that decreased while on therapy. Fourteen patients had a prolongation of PSADT compared to baseline. The prolongation was greater than a 2-fold increase in 50% of the patients. Three patients had a greater than 5-fold prolongation of the PSADT. One patient developed an asymptomatic kidney stone and was taken off study. Conclusions: Preliminary results show that weekly administration of calcitriol and naproxen is well tolerated in most patients with recurrent prostate cancer, with improvement in PSADT noted in 75% of patients. The combination therapy was successful in delaying the rate of progression in a majority of patients. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Novacea, Inc