Efficacy and safety of leuprolide acetate 6-month depot for suppression of testosterone in patients with prostate cancer

Abstract

Background:This open-label study evaluated the efficacy and safety of a new leuprolide acetate 45 mg 6-month depot formulation in 151 men with prostate cancer who received 2 intramuscular injections administered 24 weeks apart.Methods:The primary efficacy measurement was the proportion of patients achieving suppression of serum testosterone to ⩽50 ng dl−1 from week 4 through week 48. Adverse events (AEs) and hormonal and safety laboratory values were monitored.Results:The primary efficacy end point was achieved in 93.4% of subjects (95% confidence interval (89.2%, 97.6%)). There were nine escapes from testosterone suppression during the study, none of which were accompanied by a rise in PSA. By week 4, mean testosterone concentration was suppressed below castrate levels to 15.9 ng dl−1; suppression was maintained for the entire 24-week duration of each depot injection. No mean increase in testosterone was observed after the second injection. Mean PSA levels were maintained below 3 ng ml−1 from week 14 through the 48-week treatment period. The most frequent AE was flushing (58.3%). Injection site reactions were reported in 24.5% of patients.Conclusions:Leuprolide acetate 45 mg 6-month depot demonstrated rapid and sustained testosterone suppression through 12 months and was well tolerated. This 6-month leuprolide acetate depot will decrease the number of annual injections in the treatment of prostate cancer.

Extended release, 6-month formulations of leuprolide acetate for the treatment of advanced prostate cancer: achieving testosterone levels below 20 ng/dl

“…Both formulations show excellent efficacy in lowering T levels to £ 50 ng/dl at most doses. Interestingly, all formulations by end of study resulted in > 97% of patients achieving T suppression below 50 ng/dl, with the exception of the 6-month dose of IM-LA in which 93% met the target efficacy end point [31]. T breakthroughs (defined in the pivotal trials as serum T ‡ 50 ng/dl) were generally infrequent with all doses of SQ-LA and IM-LA ( Table 4).…”

“…A higher proportion of subjects who received SQ-LA experienced moderate hot flashes (24.3%) than those who received IM-LA (15.2%). There was a single severe AE that was possibly treatmentrelated reported with SQ-LA (loss of libido), whereas there were two reported with IM-LA (colonic pseudo-obstruction and angina pectoris) [31,34].…”

“…However, data available in one study that analyzed the proportion of patients with T levels £ 20 ng/dl showed that in subjects treated with 7.5 mg (1-month) IM-LA, 65.9% of subjects reached this level [32]. Recent analyses on the pivotal trials with SQ-LA showed that at end of study, 97.5, 93.7, 90.0, and 88.3%, for the 1-, 3-, 4-, 6-month formulations, respectively, were suppressed to T levels £ 20 ng/dl ( [31]. The most common adverse events (AEs), including the intensity of those events, are summarized in Table 5.…”

“…T breakthroughs (defined in the pivotal trials as serum T ‡ 50 ng/dl) were generally infrequent with all doses of SQ-LA and IM-LA ( Table 4). The only pivotal trial that had breakthroughs at a rate > 5% was the 45 mg (6-month) IM-LA trial, with breakthroughs reported in 5.4% (8/148) of patients [31].…”

Leuprorelin and Triptorelin in the treatment of Prostate Cancer: Medication adherence, Persistence and Economic Evaluation in Five Years of Analysis

“…The administration of GnRH analogs, Leuprorelin and Triptorelin, is the preferred choice for the treatment of prostate cancer [10][11][12][13]. The injection of Leuprorelin or Triptorelin reduces testosterone serum level near surgically castrated [14][15][16][17]. For this two drugs have been demonstrated to have comparable tolerability as monthly such as quarterly administration [18,19].…”