Double-blinded randomized study of high-dose calcitriol plus docetaxel compared with placebo plus docetaxel in androgen-indep..

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J Clin Oncol. 2007 Feb 20;25(6):669-74.

Comment in:
J Clin Oncol. 2008 Apr 10;26(11):1900-1; author reply 1901-2.

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, Redfern CH, Fehrenbacher L, Saleh MN, Waterhouse DM, Carducci MA, Vicario D, Dreicer R, Higano CS, Ahmann FR, Chi KN, Henner WD, Arroyo A, Clow FW; ASCENT Investigators.
of Hematology and Medical Oncology, Department of Medicine, Oregon
Health & Science University, Portland, OR 97239, USA.

To compare 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.
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
microg 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.
RESULTS: Two hundred 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 = .16). Overall, PSA response rates were 63%
(DN-101) and 52% (placebo), P = .07. Patients in the DN-101 group had a
hazard ratio for death of 0.67 (P = .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 = .07). Most common grade 3/4
toxicities for DN-101 versus placebo were neutropenia (10% v 8%),
fatigue (8% v 16%), infection (8% v 13%), and hyperglycemia (6% v 12%).

CONCLUSION: This study 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.