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

Reference
Title	Randomized, Double-Blinded Phase II Evaluation of Docetaxel with or without Doxercalciferol in Patients with Metastatic, Androgen-Independent Prostate Cancer
Topic	Vitamin D
Author	Attia, S, Eickhoff, J, Wilding, G, McNeel, D, Blank, J, Ahuja, H, Jumonville, A, Eastman, M, Shevrin, D, Glode, M, Alberti, D, Staab, MJ, Horvath, D, Straus, J, Marnocha, R, Liu, G
Year	2008
Journal	Clinical Cancer Research
DOI	https://doi.org/10.1158/1078-0432.CCR-07-4274

Author's Abstract The abstract and the information and conclusions contained therein were written by the authors of the publication.

Purpose: Docetaxel is standard of care for androgen-independent prostate cancer (AIPC). Doxercalciferol (1α-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 1:1to receive, on a 4-week cycle, docetaxel (35 mg/m2 i.v., days1, 8, and15) 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.

This publication is referenced in the following studies:

1. Attia et al. (2008): Randomized, Double-Blinded Phase II Evaluation of Docetaxel with or without Doxercalciferol in Patients with Metastatic, Androgen-Independent Prostate Cancer