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

Research output: Contribution to journalArticle

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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
Externally publishedYes

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docetaxel
Androgens
Prostatic Neoplasms
Placebos
Confidence Intervals
Prostate-Specific Antigen
Vitamin D
Disease-Free Survival
Survival
1 alpha-hydroxyergocalciferol
Standard of Care

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Randomized, double-blinded phase II evaluation of docetaxel with or without doxercalciferol in patients with metastatic, androgen-independent prostate cancer. / Attia, Steven; Eickhoff, Jens; Wilding, George; McNeel, Douglas; Blank, Jules; Ahuja, Harish; Jumonville, Alcee; Eastman, Michael; Shevrin, Daniel; Glode, Michael; Alberti, Dona; Staab, Mary Jane; Horvath, Dottie; Straus, Jane; Marnocha, Rebecca; Liu, Glenn.

In: Clinical Cancer Research, Vol. 14, No. 8, 15.04.2008, p. 2437-2443.

Research output: Contribution to journalArticle

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 2008, 'Randomized, double-blinded phase II evaluation of docetaxel with or without doxercalciferol in patients with metastatic, androgen-independent prostate cancer', Clinical Cancer Research, vol. 14, no. 8, pp. 2437-2443. https://doi.org/10.1158/1078-0432.CCR-07-4274
Attia, Steven ; Eickhoff, Jens ; Wilding, George ; McNeel, Douglas ; Blank, Jules ; Ahuja, Harish ; Jumonville, Alcee ; Eastman, Michael ; Shevrin, Daniel ; Glode, Michael ; Alberti, Dona ; Staab, Mary Jane ; Horvath, Dottie ; Straus, Jane ; Marnocha, Rebecca ; Liu, Glenn. / Randomized, double-blinded phase II evaluation of docetaxel with or without doxercalciferol in patients with metastatic, androgen-independent prostate cancer. In: Clinical Cancer Research. 2008 ; Vol. 14, No. 8. pp. 2437-2443.
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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.",
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T1 - Randomized, double-blinded phase II evaluation of docetaxel with or without doxercalciferol in patients with metastatic, androgen-independent prostate cancer

AU - Attia, Steven

AU - Eickhoff, Jens

AU - Wilding, George

AU - McNeel, Douglas

AU - Blank, Jules

AU - Ahuja, Harish

AU - Jumonville, Alcee

AU - Eastman, Michael

AU - Shevrin, Daniel

AU - Glode, Michael

AU - Alberti, Dona

AU - Staab, Mary Jane

AU - Horvath, Dottie

AU - Straus, Jane

AU - Marnocha, Rebecca

AU - Liu, Glenn

PY - 2008/4/15

Y1 - 2008/4/15

N2 - 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.

AB - 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.

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