Polymer-Delivered Leuprolide Achieves Castration-Level Testosterone
Testosterone levels of 20 ng/dL or less were achieved and maintained by more than 90% of men with advanced prostate cancer.
Leuprolide acetate delivered subcutaneously via a biodegradable polymer consistently suppresses testosterone to the same levels achieved with surgical castration among men with advanced prostate cancer (PCa), according to an analysis of 4 prospective open-label studies.
The studies enrolled men aged 40–86 years with advanced PCa who had not received prior androgen-deprivation therapy (ADT). The patients were treated with 1-, 3-, 4-, and 6-month formulations of Atrigel polymer-delivered subcutaneous leuprolide acetate (ADSC-LA): 7.5 mg (120 patients), 22.5 mg (117 patients), 30 mg (90 patients) or 45 mg (111 patients), respectively. The formulations form a solid slow-release implant after coming into contact with subcutaneous fluid.
The mean serum testosterone concentrations at the end of each study were consistently 20 ng/dL or less: 6.1, 10.1, 12.4, and 12.6 ng/dL for the 1-, 3-, 4-, and 6-month formulations, respectively, Neal D. Shore, MD, of Carolina Urologic Research Center in Myrtle Beach, S.C., and colleagues reported online ahead of print in BJU International. More than 90% of patients achieved and maintained testosterone suppression of 20 ng/dL or less over the full-dose period, the investigators reported.
“This consistent suppression of testosterone in view of the current understanding of castrate-resistant prostate cancer is clearly desirable and may represent an important metric for improving cancer-specific survival, and delaying biochemical recurrence and clinical progression in prostate cancer,” the researchers concluded.
The authors noted that achieving a serum testosterone level of 50 ng/dL or less during ADT historically has been considered the gold standard target for advanced PCa. They pointed out, however, that this level was based on the limit of sensitivity for testosterone assays at the time. More recently, using assays with improved sensitivities, some studies have shown that bilateral orchidectomy results in consistent serum testosterone levels of 20 ng/dL or less. Recent studies have demonstrated that lower serum testosterone levels during ADT are associated with improved clinical outcomes in patients with advanced PCa and biochemical failure after local therapy, Dr. Shore's group noted.