A phase II trial with new triptorelin sustained release formulations in prostatic carcinoma
Objectives:The objectives were to assess if a single intramuscular (IM) injection of the GnRH agonist triptorelin, as pamoate Sustained Release (RS) 11.25 mg, was able to induce pharmacological castration and to maintain the plasma testosterone levels in the castrate range (< 1.735 nmol/l) up to 3 months in prostatic carcinoma. Methods:Two different formulations of triptorelin pamoate 11.25 mg were assessed in 2 groups of 10 patients suffering from prostatic carcinoma. Each patient received one IM injection of triptorelin pamoate SR 11.25 mg. Triptorelin and testosterone levels were measured over 3 months. Pain, micturition difficulties, performance status, local and general tolerance, and the occurrence of adverse events were evaluated.Results: Both formulations were able to induce castration levels (< 1.735 nmol/l) of testosterone within 3 to 4 weekspost-injection, and to maintain levels below1.735 nmol/l till the end of 3rd month. The bioavailability of one formulation(DLGSD-3-95-21) tended to be greater.This may explain the quickeronset of castration and the slight better maintenance of low testosterone levels during the 3rd month observed with this formulation. In terms of clinical end-points, the local tolerance of both formulations was excellent. No serious adverse events were recorded except transient hot flushes in 2 cases and slight bone pain in one.Conclusion: Triptorelin pamoate 11.25 mg given in microgranules is a 3-month sustained-release administration form which appears to be safe and effective in advanced prostatic carcinoma. Based on the findings of this study, the formulation with greater bioavailability (DLGSD-3-95-21) was selected as formulation of choice to be used for clinical treatments and further clinical investigation.