Publication: Randomized, Double-Blinded Phase II Evaluation of Docetaxel with or without Doxercalciferol in Patients with Metastatic, Androgen-Independent Prostate Cancer
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| 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, M J, Horvath, D, Straus, J, Marnocha, R, Liu, G |
| Year | 2008 |
| Journal | Clinical Cancer Research |
| DOI | 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. |
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