Combined androgen blockade with nonsteroidal antiandrogens for advanced prostate cancer: a systematic review.
OBJECTIVE
Combined androgen blockade with medical or surgical castration plus a nonsteroidal antiandrogen for metastatic prostate cancer has been the subject of 20 randomized trials. The findings range from no expected increase in survival in 17 studies to an estimated 3.7 to 7 months' survival improvement noted in 3 studies. Most recently, a 1999 evidence report from the Agency for Healthcare Research and Quality and a 2000 overview from the Prostate Cancer Trialists Collaborative Group indicated that combined androgen blockade was associated with an approximately 3% to 5% increase in 5-year survival. We report herein a systematic review on combined androgen blockade performed by the Cochrane Collaborative Review Group on Prostate Diseases.


METHODS
Controlled trials that included a randomization of immediate nonsteroidal antiandrogens with castration versus castration alone for metastatic prostate cancer and provided information on survival were reviewed. Information on overall survival, toxicity, progression-free survival, cancer-specific survival, and type of nonsteroidal antiandrogen and castration therapies was abstracted by two independent reviewers.


RESULTS
Twenty trials (n = 6320 patients) were included. The pooled odds ratio (OR) for overall survival with combined androgen blockade was 1.03 (95% confidence interval [CI] 0.85 to 1.25; n = 4970 from 13 trials), 1.16 (95% CI 1.00 to 1.33; n = 5286 from 14 trials), and 1.29 (95% CI 1.11 to 1.50; n = 3550 from 7 trials) at 1, 2, and 5 years, respectively. Progression-free survival was improved at 1 year (OR = 1.38; 95% CI 1.15 to 1.67; n = 2278 from 7 trials). Cancer-specific survival was improved at 5 years (OR = 1.58; 95% CI 1.05 to 2.37; n = 781 from 2 trials). When analysis was limited to studies identified as being of high quality, the pooled OR for overall survival progressively increased but was not significant at any follow-up interval.


CONCLUSIONS
We find that there is a 5% improvement in the percentage of men surviving at 5 years (30% vs. 25%) with combined androgen blockade with nonsteroidal antiandrogens as well as improvements in progression-free survival at 1 year. Appropriate patients with metastatic prostate cancer should be informed of the potential benefits, toxicities, and out-of-pocket expenditures.
Schmitt
B
B
Veterans Administration Chicago Healthcare System/Lakeside Division, Chicago, Illinois, USA.
Wilt
T J
TJ
Schellhammer
P F
PF
DeMasi
V
V
Sartor
O
O
Crawford
E D
ED
Bennett
C L
CL
D000726:Androgen Antagonists / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D005485:Flutamide / Q000008:administration & dosage*; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage*; D048289:Imidazolidines; D008297:Male; D009919:Orchiectomy; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery
D000726:Androgen Antagonists; D007093:Imidazoles; D048289:Imidazolidines; C021277:nilutamide; D005485:Flutamide