Randomized, double-blinded phase II evaluation of docetaxel with or without doxercalciferol in patients with metastatic, androgen-independent prostate cancer.
OBJECTIVE
Docetaxel is standard of care for androgen-independent prostate cancer (AIPC). Doxercalciferol (1 alpha-hydroxyvitamin D2) had modest activity in phase I/II trials. Preclinical data support combining vitamin D analogues with docetaxel to treat AIPC.


METHODS
Chemotherapy-naive men with metastatic AIPC were randomized 1:1 to receive, on a 4-week cycle, docetaxel (35 mg/m2 i.v., days 1, 8, and 15) with or without doxercalciferol (10 microg orally, days 1-28). The primary end point was prostate-specific antigen (PSA) response. Secondary end points were progression-free survival, overall survival, objective response, and toxicity. Survival was analyzed as intent to treat.


RESULTS
Seventy patients were randomized. Median follow-up was 17.6 months (range, 3.3-45.2). PSA response rate was 46.7% [95% confidence interval (95% CI), 30-64] in the doxercalciferol arm and 39.4% (95% CI, 25-56) with placebo (P = 0.560). Median progression-free survival in the doxercalciferol arm was 6.17 months (95% CI, 4.20-10.7) versus 6.20 months (95% CI, 4.83-9.07) with placebo (P = 0.764). Median overall survival in the doxercalciferol arm was 17.8 months (95% CI, 14.9-23.6) versus 16.4 months (95% CI, 11.9-23.8) with placebo (P = 0.383). Twenty-four patients in the doxercalciferol arm and 23 in the placebo arm were evaluable for objective response. No complete responses were observed. Partial objective response rate was 12.5% with doxercalciferol versus 8.7% with placebo (P = 0.672). Rate of grade > or =3 toxicity was 46% with doxercalciferol versus 42% with placebo (P = 0.785).


CONCLUSIONS
Daily doxercalciferol with weekly docetaxel did not enhance PSA response rate or survival. Toxicity was similar between arms. Despite the disappointing results of this study, other vitamin D analogues remain under active investigation.
Attia
Steven
S
University of Wisconsin Paul P. Carbone Comprehensive Cancer Center, Madison, WI 53792, USA.
Eickhoff
Jens
J
Wilding
George
G
McNeel
Douglas
D
Blank
Jules
J
Ahuja
Harish
H
Jumonville
Alcee
A
Eastman
Michael
M
Shevrin
Daniel
D
Glode
Michael
M
Alberti
Dona
D
Staab
Mary Jane
MJ
Horvath
Dottie
D
Straus
Jane
J
Marnocha
Rebecca
R
Liu
Glenn
G
D000368:Aged; D000369:Aged, 80 and over; D000728:Androgens / Q000502:physiology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002118:Calcium / Q000097:blood / Q000652:urine; D000077143:Docetaxel; D004311:Double-Blind Method; D004872:Ergocalciferols / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000401:mortality; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
D000728:Androgens; D004872:Ergocalciferols; D043823:Taxoids; D000077143:Docetaxel; C042533:1 alpha-hydroxyergocalciferol; D002118:Calcium