• Hot ﬂash frequency and hot ﬂash score daily from study start until 354 days. The primary endpoint (ie, testosterone levels 0.5 ng/ml from 28–364 days) was reached (in both ITT and per-protocol analyses) and thus it was demonstrated that degarelix (240/80 and 240/160) was noninferior to leuprolide (Table 1). The number of responders in the degarelix 240/80 and 240/160 as well as the leuprolide 7.5 mg group were 202/207 patients (97.2%), 199/202 patients (98.3%), and 194/201 patients (96.4%). One of the secondary endpoints was the proportion of patients with a testosterone level 0.5 ng/ml at day 3. As expected, 96.1% and 95.5% of patients treated with degare- lix 240/80 and 240/160 had a testosterone level 0.5 ng/ml at day 3. In contrast, none of the patients in the leuprolide group achieved this result. In fact, the testosterone level in the latter group increased by 65% (median level 6.3 ng/ml, p 0.001). From days 28–364 the median testosterone levels were 0.082 ng/ml and 0.088 ng/ml in the degarelix groups and 0.078 ng/ml in the leuprolide group. In the leuprolide group 23/201 (11%) patients received a concomitant medication with bicalutamide for clinical ﬂare protection deﬁned as testosterone increase 15% from baseline on any two days during the ﬁrst two weeks. In this subgroup 17/23 (74%) had a testosterone surge and 144/178 (81%) of the patients in the leuprolide group who did not Degarelix in prostate cancer receive bicalutamide had a testosterone surge and none of the patients treated with degarelix had a testosterone surge. At days 14 and 28, PSA declined from baseline by 64%/85% and 65%/83% in the 240/80 and 240/160 degarelix groups compared to 18%/68% in the leuprolide group. These differences in PSA reduction were statistically signiﬁcant (p 0.001). Insufﬁcient response to treatment was evident in 12 patients: four and two patients (1.9% and 1%) in the degarelix 240/80 and 240/160 groups as well as six patients (3%) in the leuprolide 7.5 mg group.14 Safety The analysis of phase I, II, and III trials demonstrates that there is no evidence for allergic reaction associated with the treatment with degarelix which was the major disadvantage for clinical use of former GNRH antagonists like abarelix.14,20–22 Results from phase II trials In the North American phase II trial including 127 patients with prostate cancer (of whom 87 patients completed the study) adverse events occurred in 87% of patients receiving degare- lix 200/80 and 81% of patients receiving degarelix 200/60 (Table 2).20 Most adverse events were mild to moderate but the exact number of mild, moderate, and severe adverse events was not given. However, 13% of patients had at least one severe adverse event. The most frequent adverse events were hot ﬂashes Table 2 Published phase II and III trials on degarelix and prostate cancer: adverse events Adverse event Gittelman20 (Phase II) van Poppel21 (Phase II) degarelix 200/80 vs 200/60 degarelix 200/80 vs 200/120 vs 200/160 vs 240/80 vs 240/120 vs 240/160 Any adverse event (%) 87/81 57/66/75/63/73/67 Hot ﬂash (%) 38/48 47/25/31/37/27/33 Fatigue (%) 16/23 7/3/6/10/3/7 Injection site pain (%) 6/8 3/9/0/13/9/7 Injection site reaction (%) Not given Not given Weight increase (%) 6/6 0/9/13/13/9/7 Back pain (%) 3/9 7/9/6/3/6/3 Nasopharyngitis (%) 11/11 Not given Dizziness (%) 11/9 Not given Arthralgia (%) 6/6 Not given Constipation (%) 6/6 Not given Hypertension (%) 6/6 Not given Urinary tract infection (%) Not given 7/6/6/7/6/3 ALT increase (%) Not given 10/3/9/0/3/3 Cough (%) Not given 7/3/6/0/3/7 Diarrhea (%) Not given 3/9/6/0/3/7 Chills (%) Not given Not given Abbreviation: ALT, alanine aminotransferase. Klotz14 (Phase III) 240/80 vs 240/160 vs leuprolide 7.5 79/83/78 26/26/21 3/6/6 Not given 35/44/1 9/11/12 6/6/8 Not given Not given 5/3/9 3/5/5 6/7/4 5/1/9 10/8/5 Not given Not given 3/5/0 Clinical Interventions in Aging 2009:4 219