Randomized, double-blinded phase II evaluation of docetaxel with or without doxercalciferol in patients with metastatic, androgen-independent prostate cancer

Steven Attia, Jens Eickhoff, George Wilding, Douglas McNeel, Jules Blank, Harish Ahuja, Alcee Jumonville, Michael Eastman, Daniel Shevrin, Michael Glode, Dona Alberti, Mary Jane Staab, Dottie Horvath, Jane Straus, Rebecca Marnocha, Glenn Liu

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Abstract

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 1:1 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 ratewas 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.

Original languageEnglish (US)
Pages (from-to)2437-2443
Number of pages7
JournalClinical Cancer Research
Volume14
Issue number8
DOIs
StatePublished - Apr 15 2008

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

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. (2008). Randomized, double-blinded phase II evaluation of docetaxel with or without doxercalciferol in patients with metastatic, androgen-independent prostate cancer. Clinical Cancer Research, 14(8), 2437-2443. https://doi.org/10.1158/1078-0432.CCR-07-4274