The results of an exploratory analysis published in the March 2000
issue of Urology suggest that prolonged combined androgen blockade
(CAB) significantly increases survival in patients with advanced
A life is lost to prostate cancer every 13 minutes. The results
from our analysis suggest that the duration of CAB therapy may be an
important determinant of survival outcome, with longer being
better, said Michael F. Sarosdy, MD, South Texas Urology and
Urologic Oncology, San Antonio, Texas. Despite [the] clear
value of CAB to block both adrenal and testicular androgen sources,
long-term CAB has not been widely adopted as treatment for advanced
prostate cancer. This finding has the potential to alter practice
patterns, since the majority of physicians prescribe CAB for only the
initial 2 weeks of hormonal therapy.
Retrospective Analysis of Survival Data
The authors analyzed survival data from a previously published,
controlled trial that evaluated the efficacy and tolerability of two
antiandrogens, bicalutamide (Casodex) and flutamide (Eulexin), each
combined with a monthly depot preparation of goserelin (Zoladex) or
leuprolide (Lupron), in 813 patients with metastatic prostate cancer.
The primary objective of this retrospective analysis was to explore
whether patients who received a short course of antiandrogens as part
of CAB therapy (< 120 days) would have a different survival
outcome than those who received prolonged CAB treatment (³
120 days). The 120-day point was chosen to distinguish between short-
and long-term CAB use because, according to prescription data, this
is the average duration of antiandrogen use in the United States.
The analysis demonstrated a statistically significant survival
benefit in favor of patients receiving prolonged CAB therapy, with a
hazard ratio of 0.275 (95% confidence interval, 0.213 to 0.355; P =
.0001). The median survival of patients who received ³
120 days of CAB therapy was 1,035 days, as compared with 302 days for
patients who received < 120 days of CAB.
Second Analysis of Patient Subset Confirms Survival Benefit
To address the potential bias associated with early deaths resulting
in a short duration of therapy, a survival analysis was also
performed in the subset of patients (N = 544) who lived at least 2
years beyond the date of randomization. The median survival time of
patients who received ³ 120 days of
CAB therapy was 1,433 days, as compared with 1,061 days for patients
who received < 120 days of CAB therapy. The hazard ratio was 0.415
(95% confidence interval, 0.246 to 0.702; P = .001). This second
analysis confirmed the results of the first analysis.
This is the first analysis ever to investigate the duration of
CAB in a trial in which all patients received CAB. All others have
compared CAB to no CAB, said Dr. Sarosdy.
In clinical trials, the most commonly reported adverse events in
patients given bicalutamide (50 mg) plus a luteinizing
hormonereleasing hormone analog were hot flashes, pain, back
pain, asthenia, constipation, pelvic pain, infection, nausea,
dyspnea, peripheral edema, diarrhea, hematuria, and nocturia.
Periodic liver function tests should be considered for patients
receiving long-term therapy.