A controlled trial of bicalutamide versus flutamide, each in combination with luteinizing hormone-releasing hormone analogue therapy, in patients with advanced prostate carcinoma. Analysis of time to progression. CASODEX Combination Study Group.
BACKGROUND
A randomized, multicenter trial, double-blind for antiandrogen therapy, compared the antiandrogens bicalutamide and flutamide, each combined with luteinizing hormone-releasing hormone analogue therapy (LHRH-A) in 813 patients with Stage D2 prostate carcinoma. An analysis of time to progression (median follow-up, 95 weeks) was performed to augment previous analyses of time to treatment failure and time to death.


METHODS
Patients were randomly assigned 1:1 to double-blind antiandrogen therapy, receiving either bicalutamide (50 mg once daily) or flutamide (250 mg three times daily), and were assigned 2:1 to LHRH-A with goserelin acetate (3.6 mg every 28 days) or leuprolide acetate (7.5 mg every 28 days). The primary endpoint of the trial was time to treatment failure, defined as an adverse event leading to withdrawal of randomized therapy, objective progression, death, or withdrawal from study therapy for any reason. Secondary endpoints were time to death, quality of life, and subjective response. The current analysis of time to progression included progression data collected prospectively for 561 patients (69%) and retrospectively for 252 patients (31%).


RESULTS
Disease progression occurred for 223 of 404 patients (55%) in the bicalutamide plus LHRH-A group and for 235 of 409 patients (58%) in the flutamide plus LHRH-A group. The hazard ratio for time to progression of bicalutamide plus LHRH-A to that of flutamide plus LHRH-A was 0.9 (two-sided 95% confidence interval [CI], 0.75 to 1.08; P = 0.26). The upper one-sided 95% CI was 1.05, which met the definition of equivalence (< 1.25).


CONCLUSIONS
At a median follow-up time of 95 weeks, bicalutamide plus LHRH-A and flutamide plus LHRH-A had equivalent time to progression.
Schellhammer
P F
PF
Department of Urology, Eastern Virginia Medical School, Norfolk, Virginia, USA.
Sharifi
R
R
Block
N L
NL
Soloway
M S
MS
Venner
P M
PM
Patterson
A L
AL
Sarosdy
M F
MF
Vogelzang
N J
NJ
Chen
Y
Y
Kolvenbag
G J
GJ
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000726:Androgen Antagonists / Q000627:therapeutic use*; D000813:Anilides / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D004311:Double-Blind Method; D005485:Flutamide / Q000627:therapeutic use*; D017273:Goserelin / Q000627:therapeutic use*; D006801:Humans; D016729:Leuprolide / Q000627:therapeutic use; D008297:Male; D009570:Nitriles; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D014105:Tosyl Compounds
D000726:Androgen Antagonists; D000813:Anilides; D018931:Antineoplastic Agents, Hormonal; D009570:Nitriles; D014105:Tosyl Compounds; D017273:Goserelin; D005485:Flutamide; C053541:bicalutamide; D016729:Leuprolide