Double-blinded randomized study of high-dose calcitriol plus docetaxel compared with placebo plus docetaxel in androgen-independent prostate cancer: A report from the ASCENT investigators: Beer TM, Ryan CW, Venner PM, Petrylak DP, Chatta GS, Ruether JD, R

Purpose pare the safety and activity of DN-101, a new high-dose oral formulation of calcitriol designed for cancer therapy, and docetaxel with placebo and docetaxel. ts and methods ts with progressive metastatic androgen-independent prostate cancer and adequate organ function received weekly docetaxel 36 mg/m2 intravenously for 3 weeks of a 4-week cycle combined with either 45 μg DN-101 or placebo taken orally 1 day before docetaxel. The primary end point was prostate-specific antigen (PSA) response within 6 months of enrollment, defined as a 50% reduction confirmed at least 4 weeks later. s ndred fifty patients were randomly assigned. Baseline characteristics were similar in both arms. Within 6 months, PSA responses were seen in 58% in DN-101 patients and 49% in placebo patients (P = 0.16). Overall, PSA response rates were 63% (DN-101) and 52% (placebo), P = 0.07. Patients in the DN-101 group had a hazard ratio for death of 0.67 (P = 0.04) in a multivariate analysis that included baseline hemoglobin and performance status. Median survival has not been reached for the DN-101 arm and is estimated to be 24.5 months using the hazard ratio, compared with 16.4 months for placebo. Grade 3/4 adverse events occurred in 58% of DN-101 patients and in 70% of placebo-treated patients (P = 0.07). Most common grade 3/4 toxicities for DN-101 vs. placebo were neutropenia (10% vs. 8%), fatigue (8% vs. 16%), infection (8% vs. 13%), and hyperglycemia (6% vs. 12%). sion tudy suggests that DN-101 treatment was associated with improved survival, but this will require confirmation because survival was not a primary end point. The addition of weekly DN-101 did not increase the toxicity of weekly docetaxel.