Memorial Sloan-Kettering Cancer Center, 1275 York Avenue Between 67th and 68th Streets New York, NY.
Joan and Sanford E. Weill College of Medicine of Cornell University, New York, NY; British Columbia Cancer Agency-Vancouver Cancer Center, Vancouver, British Columbia; Cross Cancer Institute, Edmonton; Tom Baker Cancer Center, Calgary, Alberta, Canada; Eramus University Medical Center, Rotterdam, the Netherlands; Cancer Centers of North Carolina, Cary, NC; University of Düsseldorf, Düsseldorf; RWTH Aachen University, Aachen, Germany; FL Cancer Specialists, Sarasota, FL; Oncology Hematology Care, Inc, Cincinnati, OH; Tower Cancer Research Foundation, Beverly Hills, CA; Sarah Cannon Canter Cancer Center, Nashville, TN; and the NE Methodist Hospital, Omaha, NE.
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.
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.
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%).
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.
Written by:
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. Are you the author?
Reference: J Clin Oncol. 2011 Apr 11. Epub ahead of print.
doi: 10.1200/JCO.2010.32.8815
PubMed Abstract
PMID: 21483004
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