A controlled trial of bicalutamide versus flutamide, each in combination with luteinizing hormone-releasing hormone analogue therapy, in patients with advanced prostate cancer. Casodex Combination Study Group.
OBJECTIVE
To compare the efficacy and safety of bicalutamide and flutamide, each used in combination with luteinizing hormone-releasing analogue (LHRH-A) therapy, in patients with untreated metastatic (Stage D2) prostate cancer.


METHODS
Randomized, double-blind (for antiandrogen therapy), multicenter study with a 2 x 2 factorial design. Eight hundred thirteen patients were allocated 1:1 to bicalutamide (50 mg once daily) and flutamide (250 mg three times daily) and 2:1 to goserelin acetate (3.6 mg every 28 days) and leuprolide acetate (7.5 mg every 28 days).


RESULTS
With a median duration of follow-up of 49 weeks, time to treatment failure, the primary endpoint, was significantly (P = 0.005) better for the bicalutamide plus LHRH-A group than for the flutamide plus LHRH-A group. Patients in the flutamide plus LHRH-A group were 34% more likely to fail treatment over the given time period, as indicated by the hazard ratio of 0.749 (95% confidence interval, 0.61 to 0.92) for bicalutamide plus LHRH-A to flutamide plus LHRH-A. Results for secondary endpoints (survival, quality of life, and subjective response) were similar between groups. Diarrhea occurred in 24% of patients in the flutamide plus LHRH-A group, compared with 10% of patients in the bicalutamide plus LHRH-A group (P < 0.001).


CONCLUSIONS
In patients with metastatic prostate cancer, bicalutamide plus LHRH-A is well tolerated and provides superior efficacy to flutamide plus LHRH-A with respect to time to treatment failure. Assessment of the effects of these regimens on longer term survival requires additional time for follow-up.
Schellhammer
P
P
Eastern Virginia Medical School, Norfolk, USA.
Sharifi
R
R
Block
N
N
Soloway
M
M
Venner
P
P
Patterson
A L
AL
Sarosdy
M
M
Vogelzang
N
N
Jones
J
J
Kolvenbag
G
G
D000230:Adenocarcinoma / Q000097:blood / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000813:Anilides / Q000008:administration & dosage / Q000009:adverse effects; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016001:Confidence Intervals; D004311:Double-Blind Method; D005485:Flutamide / Q000008:administration & dosage / Q000009:adverse effects; D005500:Follow-Up Studies; D017273:Goserelin / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D016729:Leuprolide / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009570:Nitriles; D016016:Proportional Hazards Models; D011446:Prospective Studies; D017430:Prostate-Specific Antigen / Q000097:blood / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D012044:Regression Analysis; D015996:Survival Rate; D014105:Tosyl Compounds; D017211:Treatment Failure
D000813:Anilides; D000970:Antineoplastic Agents; D009570:Nitriles; D014105:Tosyl Compounds; D017273:Goserelin; D005485:Flutamide; C053541:bicalutamide; D017430:Prostate-Specific Antigen; D016729:Leuprolide