• Time to PSA progression (deﬁned as PSA increase of 50% or more from nadir and at least 5 ng/ml on two consecutive visits at least two weeks apart) • Pharmacodynamic parameters such as testosterone, PSA, dihydrotestosterone (DHT), LH, and FSH over time. There were 23 patients with protocol violations, 16 with- drawals due to inadequate testosterone suppression, six withdrawals due to adverse events, and 18 withdrawals due to other reasons. Therefore, 87/127 patients (69%) completed the study. Arm A comprised of 42 patients and arm B of 45 patients without differences with regard to demographics and baseline characteristics. Median PSA at baseline was 13.4 ng/ml (25th–75th percentile: 6.8–25.7 ng/ml). Median testosterone level at baseline was 4.13 ng/ml (25th–75th percentile: 3.06–5.11 ng/ml). Tumor stages were localized in 43%, locally advanced in 11%, metastatic in 19%, and not classiﬁable in 28% of patients. The Gleason score was 2–4 in 5%, 5–6 in 32%, and 7–10 in 63% of cases, respectively. In this study no testosterone surge was observed. At day 3, 89% of all patients had a testosterone 0.5 ng/ml without a statistically signiﬁcant difference between both groups (Table 1). After one month 88% of all patients had a testosterone 0.5 ng/ml (93% of patients in arm A compared to 83% of patients in arm B p = 0.073). The authors concluded that the starting dose was too low to achieve the predeﬁned Degarelix in prostate cancer efﬁcacy success criterion of 95% of patients with a testosterone level 0.5 ng/ml. This was the rationale to test 240 mg as a starting dose in subsequent trials. Only 86% of patients in arm A and 77% of patients in arm B remained with their tes- tosterone 0.5 ng/ml during the entire study period (p = not signiﬁcant, exact p value not given in publication). However, the majority of patients who had a testosterone 0.5 ng/ml after one month remained within this range for the entire study period (93% of patients in arm A compared to 98% of patients in arm B; p = 0.669). A PSA decline of 50% and 90% was achieved after 14 and 56 days in both treatment groups and a median reduction of 96% was documented after 12 months.20 The second study was conducted in Europe and South Africa and screened 216 patients with prostate cancer of whom 189 were randomized and 187 received study medication.21 Median age was 72 years (range 52–93 years). The inclusion criteria were similar to that in the North American study.20 Patients were randomized to six different dose regimens with an initial dosage of 200 mg degarelix or 240 mg degarelix followed by monthly maintenance dosage of degarelix 80 mg, degarelix 120 mg, or degarelix 160 mg (groups 200/80, 200/120, 200/160, 240/80, 240/120, 240/160), respectively. In all groups, a concentration of 40 mg/ml degarelix was used. Thus, the sc injected volume varied between 2 ml and 4 ml. Table 1 Published phase II and III trials on degarelix and prostate cancer: Efﬁcacy Author Patients Study design Gittelman20 N = 127 Phase II Efﬁcacy and safety of degarelix with a starting dose of 200 mg followed by monthly maintenance doses of 60 mg or 80 mg for one year. van Poppel21 N = 187 Klotz14 N = 610 Abbreviation: PSA, prostate-speciﬁc antigen. Clinical Interventions in Aging 2009:4 Phase II Efﬁcacy and safety of degarelix with a 200 mg or 240 mg starting dose followed by monthly maintenance doses of 80 mg, 120 mg, or 160 mg for one year. Phase III Efﬁcacy and safety of degarelix with a starting dose of 240 mg followed by monthly maintenance dose of 80 mg or 160 mg vs leuprolide 7.5 mg monthly. Results Testosterone suppression: 88% after one month, 93% and 98% (60 mg and 80 mg) after one year. PSA response: Median reduction 96% after one year Testosterone suppression: 86% (200 mg) vs 95% (240 mg) after one month, 92% (80 mg), 96% (120 mg), 100% (160 mg) after one year. PSA response: Median reduction 97%–98% after one year Testosterone suppression: 97.2%, 98.3% in patients treated with degarelix (240/80 mg, 240/160 mg) and 96.4% in patients treated with leuprolide after one year. PSA response: PSA decline from baseline was signiﬁcant faster in the degarelix groups than with leuprolide, PSA values not given in publication. 217