Phase II trial of high‐dose, intermittent calcitriol (1,25 dihydroxyvitamin D3) and dexamethasone in androgen‐independent prostate cancer

BACKGROUND Data suggest that vitamin D plays a role in the treatment and prevention of prostate cancer. The combination of high‐dose, intermittent calcitriol (1,25 dihydroxyvitamin D3) plus dexamethasone was studied based on evidence that dexamethasone potentiates the antitumor effects of calcitriol and ameliorates hypercalcemia. METHODS Oral calcitriol was administered weekly, Monday, Tuesday, and Wednesday (MTW), at a dose of 8 μg, for 1 month, at a dose of 10 μg every MTW for 1 month, and at a dose of 12 μg every MTW thereafter. Dexamethasone at a dose of 4 mg was administered each Sunday, and MTW weekly. Calcium and creatinine were determined weekly and radiographs of the urinary tract were performed every 3 months. All patients were considered evaluable for toxicity. RESULTS Forty‐three men with androgen‐independent prostate cancer were entered; 37 received at least 1 month of calcitriol given at a dose of 12 μg every day × 3 per week. The majority of patients had bone metastases and rising prostate‐specific antigen (PSA) levels. All had an Eastern Cooperative Oncology Group performance status of 0 or 1. Eight patients (19%) experienced partial responses by PSA criterion (PSA decline of ≥50%, persisting for ≥28 days). Subjective clinical improvement occurred in some patients. Toxicity was minimal: urinary tract stones in 2 patients; and a readily reversible, CTC (v.3.0) Grade 11.0 mg/dL and no patient had a calcium level >12.0 mg/dL. CONCLUSIONS The response rate reported in the current study (19%) was not found to be clearly higher than expected with dexamethasone alone. High‐dose intermittent calcitriol plus dexamethasone appears to be safe, feasible, and has antitumor activity. Cancer 2006. © 2006 American Cancer Society. Epidemiologic and preclinical data indicate that calcitriol may be important in controlling the growth of prostate cancer. A Phase II study in patients with androgen‐independent prostate cancer, in which calcitriol at a dose of 12 μg was given Monday, Tuesday, and Wednesday weekly and dexamethasone at a dose of 4 mg was given Sunday, Monday, Tuesday, and Wednesday weekly, disclosed a prostate‐specific antigen response rate of 19% and no limiting toxicity.