Low incidence of microsurges with biodegradable polymer-delivered, subcutaneously-administered leuprolide acetate in prostate cancer patients.

Abstract

158 Background: Androgen deprivation therapy is a foundational treatment of advanced prostate cancer (PCa) with the primary objective of suppressing circulating androgens.Consistent drug delivery with long-acting leuprolide acetate (LA) formulations is important in providing continuous testosterone (T) suppression throughout the course of treatment without T rising above castrate level (T breakthrough). To assess subcutaneously-administered LA (SC-LA) maintenance of T levels in PCa patients, the incidence of microsurges was evaluated in 4 pivotal trials. Methods: In 4 open-label, fixed-dose, pivotal trials, 424 eugonadal prostate cancer patients (age 40-86) who achieved medical castration (T<50 ng/dL) while on the first administration of SC-LA 7.5, 22.5, 30, or 45 mg, lasting 1, 3, 4, or 6 months, respectively, were evaluated for microsurges. A microsurge was defined as an absolute increase in T level of at least 25 ng/dL during the 4 week period after the second study dose was administered. T was measured 2-4 times on day 0 and once on days 1, 2, 3, 7, and every week until the next dose through the end of the studies. Results: Across the individual studies, 8 patients out of 424 (range 0.9-3.4% by dose, pooled 1.9%) experienced a microsurge during the acute period after the second SC-LA dose (Table). 6 of these 8 patients remained below castrate level at the peak of the surge. Conclusions: SC-LA demonstrated a very low incidence of T breakthroughs and microsurges in PCa patients and only 2 of 424 patients experienced a T microsurge above castrate levels. Limiting the occurrence of T levels above castrate levels may have clinical implications with respect to prolonged progression-free survival. [Table: see text]