PHARMACODYNAMIC EQUIVALENCE OF USING 3-MONTH AND 28-DAY SUSTAINED-RELEASE DECAPEPTYL DEPOT FORMULATIONS IN PATIENTS WITH ADVANCED PROSTATE CANCER

Abstract

Objective: to evaluate the pharmacodynamic equivalence of 3-month and 28-day formulations of tryptoreline, a sustained-release luteininghormone (LH)-releasing hormone analogue.

Subjects and methods. The patients who had a verified diagnosis of locally advanced or metastatic prostate cancer were randomized intogroups to have either one injection of a 3-month dosage form (n = 63) or 3 injections of a 28-day formulation at 28-day intervals (n = 68).The onset rate of drug-induced castration, which was defined as a percentage of the patients achieving a plasma testosterone level of ≤0.5ng/ml, was compared on day 84 (i.e. thrice every 28 days). The plasma profiles of testosterone, LH, and tryptoreline, as well as the changesin the plasma concentration of prostate-specific antigen (PCA) from the baseline values were estimated within 3 months (from the initiationof therapy to day 91).

Results. In the 3-month and 28-day groups, the onset rate of drug-induced castration was 98 and 96%, respectively (at confidenceintervals (94.2% bilaterally) in [-8.1%; 9.6%]. The median time for drug-induced castration was 18.8 and 18.5 days, respective-ly (p = 0.86; log-rank test). The ratios of the mean peak plasma concentrations to AUC91 of the two formulations for testosteroneand LH were within 0.80; 1.25 equivalence interval. By day 91, the mean PSA level was decreased by 91.0 and 91.7%, respec-tively (p = 0.73).

Conclusion. The use of the two formulations during 3 months is pharmacologically equal.