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Randomized, Double-Blinded Phase II Evaluation of Docetaxel with or without Doxercalciferol in Patients with Metastatic, Androgen-Independent Prostate Cancer

Authors' Affiliations: ¹ University of Wisconsin Paul P. Carbone Comprehensive Cancer Center, Madison, Wisconsin; ² Green Bay Oncology, Green Bay, Wisconsin; ³ Aspirus Wausau Hospital, Wausau, Wisconsin; ⁴ Gundersen Clinic, La Crosse, Wisconsin; ⁵ L.C. Ferguson Cancer Center, Freeport, Illinois; ⁶ Evanston Northwestern Healthcare, Evanston, Illinois; and ⁷ University of Colorado Health Sciences Center, Aurora, Colorado

Requests for reprints: Glenn Liu, University of Wisconsin Paul P. Carbone Comprehensive Cancer Center, 600 Highland Avenue, K6/534, Madison, WI 53792. Phone: 608-265-8689; Fax: 608-265-8133; E-mail: gxl{at}medicine.wisc.edu.

Purpose: Docetaxel is standard of care for androgen-independent prostate cancer (AIPC). Doxercalciferol (1-hydroxyvitamin D2) had modest activity in phase I/II trials. Preclinical data support combining vitamin D analogues with docetaxel to treat AIPC.

Experimental Design: Chemotherapy-naive men with metastatic AIPC were randomized 1:1 to receive, on a 4-week cycle, docetaxel (35 mg/m² i.v., days 1, 8, and 15) with or without doxercalciferol (10 µg orally, days 1-28). The primary end point was prostate-specific antigen (PSA) response. Secondary end points were progression-free survival, overall survival, objective response, and toxicity. Survival was analyzed as intent to treat.

Results: Seventy patients were randomized. Median follow-up was 17.6 months (range, 3.3-45.2). PSA response rate was 46.7% [95% confidence interval (95% CI), 30-64] in the doxercalciferol arm and 39.4% (95% CI, 25-56) with placebo (P = 0.560). Median progression-free survival in the doxercalciferol arm was 6.17 months (95% CI, 4.20-10.7) versus 6.20 months (95% CI, 4.83-9.07) with placebo (P = 0.764). Median overall survival in the doxercalciferol arm was 17.8 months (95% CI, 14.9-23.6) versus 16.4 months (95% CI, 11.9-23.8) with placebo (P = 0.383). Twenty-four patients in the doxercalciferol arm and 23 in the placebo arm were evaluable for objective response. No complete responses were observed. Partial objective response rate was 12.5% with doxercalciferol versus 8.7% with placebo (P = 0.672). Rate of grade 3 toxicity was 46% with doxercalciferol versus 42% with placebo (P = 0.785).

Conclusions: Daily doxercalciferol with weekly docetaxel did not enhance PSA response rate or survival. Toxicity was similar between arms. Despite the disappointing results of this study, other vitamin D analogues remain under active investigation.