Phase II study of all-trans retinoic acid administered intermittently for hormone refractory prostate cancer

Purpose: We assess the efficacy and toxicity of all-trans retinoic acid administered intermittently for hormone refractory prostate cancer. Materials and Methods: A total of 26 patients with histologically con firmed adenocarcinoma of the prostate and manifestations of progressive metastatic disease, despite at least 1 hormonal therapy, were included in the study. Patients received a single oral dose of 45 mg./m.(2) all-trans retinoic acid daily for 7 days followed by 7 days of no treatment, and then resumed treatment on day 14. This schedule was continued until progression or limiting toxicity occurred. Response was assessed based on serial measurements of serum prostate specific antigen and pain scores every other week. In addition, objective responses were evaluated every 12 weeks in patients with bi-dimensionally measurable metastases. Results: All-trans retinoic acid was administered for 168 weeks (median 6 weeks per patient, range 2 to 21). Toxicity was mild. No patient stopped therapy because of toxicity. Of the patients 4 (15%) demonstrated a biological response of 50% or greater serum prostate specific antigen decrease. No objective response was observed among 11 patients with measurable metastases. Of 17 patients who required analgesics at the onset of all-trans retinoic acid treatment only 1 achieved a significant reduction of pain. Median survival time from the onset of all-trans retinoic acid treatment was 19 months (range 2 to 24). Conclusions: All-trans retinoic acid has minimal activity in hormone refractory prostate cancer.