MULTIVARIATE-ANALYSIS OF PLASMA HORMONES IN PATIENTS WITH METASTATIC PROSTATE-CANCER RECEIVING COMBINED LHRH-ANALOG AND ANTIANDROGEN THERAPY

The following hormones, the plasma protein SHBG, and the tumor markers prostatic acid phosphatase (PAP) and prostate-specific antigen (PSA) were assayed at 18 time-points over 1 month during a double-blind rand omized study in 36 stage D-2 cancer patients receiving either ''busere lin + placebo'' or ''buserelin + nilutamide (Anandron)'': LH, FSH, est radiol, testosterone, dihydrotestosterone, androstenedione, 5-androste ne-3, 17 beta-diol, dehydroepiandrosterone and its sulfate, cortisol, 17 alpha-hydroxyprogesterone, pregnenolone, 17 alpha-hydroxypregnenolo ne, and 3 alpha-androstanediol glucuronide. Multivariate analysis of t he treatment values (over 10,000 assays) by two complementary methods, correspondence factorial analysis (CFA) and the minimum spanning tree (MST) method, identified those variables within the pathways of andro gen metabolism that were correlated over time and, in a comparison of the two treatment groups, identified the enzyme targets of nilutamide action in humans. Whereas nilutamide tended to decrease androstenedion e slightly, it affected no other variables including cortisol, except for pregnenolone, 17 alpha-OH-pregnenolone, and 17 alpha-OH-progestero ne, which were increased. These increases are indicative of weak inhib ition of C17,20 lyase by nilutamide, but, according to the multivariat e analysis, are insufficient to account for the more marked and rapid fall in FAP and PSA noted on addition of nilutamide to buserelin that must therefore be explained by another mechanism such as androgen rece ptor blockade by nilutamide. (C) 1993 Wiley-Liss, Inc.