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.
OBJECTIVE
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.


METHODS
Patients 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 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%).


CONCLUSIONS
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.
Beer
Tomasz M
TM
Division of Hematology and Medical Oncology, Department of Medicine, Oregon Health & Science University, Portland, OR 97239, USA. beert@ohsu.edu
Ryan
Christopher W
CW
Venner
Peter M
PM
Petrylak
Daniel P
DP
Chatta
Gurkamal S
GS
Ruether
J Dean
JD
Redfern
Charles H
CH
Fehrenbacher
Louis
L
Saleh
Mansoor N
MN
Waterhouse
David M
DM
Carducci
Michael A
MA
Vicario
Daniel
D
Dreicer
Robert
R
Higano
Celestia S
CS
Ahmann
Frederick R
FR
Chi
Kim N
KN
Henner
W David
WD
Arroyo
Alan
A
Clow
Fong W
FW
D000367:Age Factors; D000368:Aged; D000728:Androgens / Q000378:metabolism*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001707:Biopsy, Needle; D002117:Calcitriol / Q000008:administration & dosage* / Q000009:adverse effects; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010919:Placebos / Q000008:administration & dosage; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D018570:Risk Assessment; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
D000728:Androgens; D010919:Placebos; D043823:Taxoids; D000077143:Docetaxel; D017430:Prostate-Specific Antigen; D002117:Calcitriol