Why phase III trials of maximal androgen blockade versus castration in M1 prostate cancer rarely show statistically significant differences.
BACKGROUND
The meta-analysis of maximal androgen blockade (MAB) concluded that there is no survival advantage of MAB over castration alone. However, the results from the largest trials yield conflicting results.


METHODS
The design and results of three trials were examined.


RESULTS
Most studies were planned to detect an over-optimistic difference in survival and immature data were published. The survival curves show that statistical assumptions are not fulfilled. Excluding from the meta-analysis all trials where a negative impact of disease flare on survival could not be excluded resulted in no difference in survival between MAB and castration.


CONCLUSIONS
Trials of MAB should be planned to detect differences of no more than 5-10% in median survival. The analyses should only be carried out on mature data and should take into account the possibility of a negative impact on survival due to disease flare if no anti-androgen has been given initially with an LH-RH agonist.
Collette
L
L
European Organization for Research and Treatment of Cancer, EORTC Data Center, Brussels, Belgium. lco@eortc.be
Studer
U E
UE
Schröder
F H
FH
Denis
L J
LJ
Sylvester
R J
RJ
D000726:Androgen Antagonists / Q000627:therapeutic use*; D000813:Anilides / Q000627:therapeutic use; D017326:Clinical Trials, Phase III as Topic; D017373:Cyproterone Acetate / Q000627:therapeutic use; D005163:Factor Analysis, Statistical; D005485:Flutamide / Q000627:therapeutic use; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists; D017273:Goserelin / Q000627:therapeutic use; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use; D048289:Imidazolidines; D016729:Leuprolide / Q000627:therapeutic use; D008297:Male; D015201:Meta-Analysis as Topic; D009570:Nitriles; D009919:Orchiectomy; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000628:therapy*; D012107:Research Design; D016019:Survival Analysis; D014105:Tosyl Compounds; D016896:Treatment Outcome
D000726:Androgen Antagonists; D000813:Anilides; D007093:Imidazoles; D048289:Imidazolidines; D009570:Nitriles; D014105:Tosyl Compounds; D017273:Goserelin; D007987:Gonadotropin-Releasing Hormone; D017373:Cyproterone Acetate; C021277:nilutamide; D005485:Flutamide; C053541:bicalutamide; D016729:Leuprolide