Randomized, open-label phase III trial of docetaxel plus high-dose calcitriol versus docetaxel plus prednisone for patients with castration-resistant prostate cancer.

Published

Journal Article

PURPOSE: To compare the efficacy and safety of docetaxel plus high-dose calcitriol (DN-101) to docetaxel plus prednisone in an open-label phase III trial. PATIENTS AND METHODS: Nine hundred fifty-three men with metastatic castration-resistant prostate cancer (CRPC) were randomly assigned to Androgen-Independent Prostate Cancer Study of Calcitriol Enhancing Taxotere (ASCENT; 45 μg DN-101, 36 mg/m(2) docetaxel, and 24 mg dexamethasone weekly for 3 of every 4 weeks) or control (5 mg prednisone twice daily with 75 mg/m(2) docetaxel and 24 mg dexamethasone every 3 weeks) arms. The primary end point was overall survival (OS), assessed by the Kaplan-Meier method. RESULTS: At an interim analysis, more deaths were noted in the ASCENT arm, and the trial was halted. The median-follow-up for patients alive at last assessment was 11.7 months. Median OS was 17.8 months (95% CI, 16.0 to 19.5) in the ASCENT arm and 20.2 months (95% CI, 18.8 to 23.0) in the control arm (log-rank P = .002). Survival remained inferior after adjusting for baseline variables (hazard ratio, 1.33; P = .019). The two arms were similar in rates of total and serious adverse events. The most frequent adverse events were GI (reported in 75% of patients), and blood and lymphatic disorders (48%). Docetaxel toxicity leading to dose modification was more frequent in the ASCENT (31%) than in the control arm (15%). CONCLUSION: ASCENT treatment was associated with shorter survival than the control. This difference might be due to either weekly docetaxel dosing, which, in a prior study, showed a trend toward inferior survival compared with an every-3-weeks regimen, or DN-101 therapy.

Full Text

Duke Authors

Cited Authors

  • Scher, HI; Jia, X; Chi, K; de Wit, R; Berry, WR; Albers, P; Henick, B; Waterhouse, D; Ruether, DJ; Rosen, PJ; Meluch, AA; Nordquist, LT; Venner, PM; Heidenreich, A; Chu, L; Heller, G

Published Date

  • June 2011

Published In

Volume / Issue

  • 29 / 16

Start / End Page

  • 2191 - 2198

PubMed ID

  • 21483004

Pubmed Central ID

  • 21483004

Electronic International Standard Serial Number (EISSN)

  • 1527-7755

International Standard Serial Number (ISSN)

  • 0732-183X

Digital Object Identifier (DOI)

  • 10.1200/jco.2010.32.8815

Language

  • eng