Polymer-delivered subcutaneous leuprolide acetate formulations achieve and maintain castrate concentrations of testosterone in four open-label studies in patients with advanced prostate cancer

Objective To determine whether luteinising hormone-releasing hormone (LHRH) agonist, ATRIGEL (R) polymer-delivered, subcutaneous, leuprolide acetate (ADSC-LA), formulations suppressed serum testosterone to concentrations of <= 20 ng/dL. Patients and Methods Data from four open-label, fixed-dose studies were evaluated. Male patients aged 40-86 years with advanced prostatic adenocarcinoma, whom had not undergone prior androgen-deprivation therapy (ADT), were treated with a depot formulation of ADSC-LA: 7.5 mg (1-month, 120 patients), 22.5 mg (3-month, 117 patients), 30 mg (4-month, 90 patients), or 45 mg (6-month, 111 patients). Serum testosterone was sampled at screening, baseline, 2, 4, 8 h after dosing, 1, 2, 3, and 7 days, and every week until the next dose, at which time, the sampling schedule repeated until the end of study (24 weeks for 1-and 3-month formulations, 32 weeks for 4-month, and 48 weeks for the 6month). The primary analyses were mean serum testosterone concentrations and proportion of patients who achieved concentrations of <= 20 ng/dL. Results The mean (SE) serum testosterone concentrations at the end of study were consistently <= 20 ng/dL in each study, at 6.1 (0.4), 10.1 (0.7), 12.4 (0.8), and 12.6 (2.1) ng/dL for the 1-, 3-, 4-, and 6-month formulations, respectively. A high proportion of patients (94%, 90%, 92%, 96% for the 1-, 3-, 4-, and 6-month formulations, respectively) achieved testosterone concentrations of <= 20 ng/dL within 6 weeks, and 90-97% of patients in all studies maintained concentrations of <= 20 ng/dL from weeks 6-24. Conclusions Recent studies have shown improved outcomes in patients with prostate cancer who consistently attained a more rigorous level of testosterone suppression (<= 20 ng/ dL) with ADT than the historical standard (<= 50 ng/ dL). All doses of ADSC-LA rapidly achieved and maintained mean serum testosterone to the more rigorous target concentration of <= 20 ng/ dL. These data suggest that ADSC-LA delivers equivalent testosterone suppression as achieved by surgical castration.