Objectives: Two innovative pharmaceutical forms of leuprorelin acetate have been developed as 1-month and 3-month implants for the treatment of advanced hormone-dependent prostate cancer. These products contain active substance dispersed homogeneously in a biodegradable polymer. Here we present the key results from the clinical development of these slow-release implant formulations of leuprorelin. Methods: Two therapeutic studies of the 1-month implant were performed: a randomized, controlled study comparing the leuprorelin implant with leuprorelin prolonged-release microspheres (Enantone) as the active control; and a single-arm study of the leuprorelin implant. For the 3-month implant, four therapeutic studies were performed: a randomized, controlled study comparing the leuprorelin implant with leuprorelin prolonged-release microspheres (Trenantone) as the active control; a single-arm study of the leuprorelin implant; and two long-term studies with the 3-month implant administered twice, either 12 or 16 weeks apart. A pooled analysis of data from the comparator-controlled and single-arm studies of the 3-month implant was also conducted. The main inclusion criterion for all studies was histologically confirmed advanced prostate cancer, with primary endpoints based around successful testosterone suppression (≤0.5 ng/ml). Results: In the comparator-controlled studies, both implants were as effective as the microspheres for achieving successful testosterone suppression and normalization of prostate-specific antigen (PSA) levels. Data from the single-arm and long-term studies were consistent with those from the comparator-controlled studies. In the pooled analysis, significantly more patients treated with the 3-month implant achieved successful testosterone suppression compared with the comparator ( p ≤ 0.01). The safety profile of the implants in the comparator-controlled studies was similar to that of the prolonged-release microsphere formulation, and consistent with that of the luteinizing hormone-releasing hormone agonist class. Conclusions: The innovative 1-month and 3-month implants of leuprorelin acetate are at least as effective as leuprorelin acetate prolonged-release microspheres for achieving successful testosterone suppression and normalization of PSA in men with advanced hormone-dependent prostate cancer, with a comparable safety profile.

Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), a PRO instrument specifically designed to measure HRQoL of cancer patients. HRQoL was measured at screening, months 1, 3, 7, and at re-puncture. Meaningful deterioration was defined as a decrease in HRQoL scores of at least 5 points. Time to first meaningful deterioration was compared between catumaxomab (Nϭ160) and control (Nϭ85) groups using survival analysis techniques such as log-rank test and Cox models. RESULTS: Deterioration in HRQoL scores appeared more rapidly in the control group than the catumaxomab group (medians: 16-28 days vs. 45-49 days). The difference between the two groups in time to deterioration in HRQoL was statistically significant for all scores (pϽ0.01). Results were confirmed with Cox models (pϽ0.05). Hazard ratios ranged from 0.08 to 0.24. CONCLUSIONS: Treatment with catumaxomab delayed deterioration in HRQoL in patients with MA compared to paracentesis alone. The findings of this study indicate that the gain of puncture free survival due to catumaxomab treatment previously reported (Heiss et al. 2010) translates into a HRQoL benefit for the patients. OBJECTIVES:The majority of patients with prostate cancer progress to CRPC and frequently develop bone metastases. Treatment and management of bone metastases, as well as the underlying disease, influences the patient's quality of life. We evaluated the impact of bone metastases on utility (using EQ-5D) and quality of life (using FACT-P) in high-risk CRPC patients. METHODS: Data were extracted from the Adelphi Real World Prostate Cancer Disease-Specific Programme© (DSP), a cross-sectional survey of 348 urologists and oncologists and their prostate cancer patients that was conducted between and the UK. Physicians completed comprehensive record forms on 10 patients being actively treated for prostate cancer. Patients could also complete a questionnaire, which included the EQ-5D and FACT-P tools, however this was not compulsory. RESULTS: Of the 3,477 prostate cancer patients for which data were collected, 1,180 (34%) were categorised as having CRPC with a median time since diagnosis of 35.8 months. 146 patients with CRPC were identified as being at high risk for developing bone metastases (Gleason score Ն8, or a most recent PSA of Ն8ng/mL, or a PSA DT Յ10 months, or had received local therapy in addition to systemic medication). High-risk CRPC patients had an average EQ-5D index of 0.77 (nϭ36) and FACT-P of 99.54 (nϭ27). In contrast, patients with CRPC and bone metastases (nϭ680) had an average EQ-5D index of 0.59 (nϭ165) and FACT-P of 82.99 (nϭ147). Statistical differences were observed between the highrisk and bone metastases groups for both EQ-5D (pϭ0.0002) and FACT-P (pϭ0.0007). CONCLUSIONS: The development of bone metastases represents a significant additional burden for patients with CRPC highlighting the need for new treatments capable of preventing bone metastases in these patients.

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