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P111 Final results of phase II study of Gemcitabine-Oxalipaltin (GemOx) plus Prednisolone in patients with Castration-Resistant Prostate Cancer (CRPC) for whom Docetaxel-based chemotherapy failed
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A B S T R A C T S / E U R O P E A N U R O L O G Y S U P P L E M E N T S 12 (2013) 123–180
lustrates the current pattern of MDT cooperation in Poland. Noninterventional study DIREG_L_02709 was sponsored by SanofiAventis. P111 Final results of phase II study of Gemcitabine-Oxalipaltin (GemOx) plus Prednisolone in patients with Castration-Resistant Prostate Cancer (CRPC) for whom Docetaxel-based chemotherapy failed Lee 1 ,
Ahn 1 ,
Choi 1 ,
Kim 1 ,
Hong 1 ,
J.-H. M. Y. S.-W. J.-L. I.-G. Jeong 2 , C. Song 2 , B.-S. Hong 2 , J.H. Hong 2 , H. Ahn 2 . 1 Asan Medical Center, University of Ulsan College of Medicine, Dept. of Oncology, Seoul, South Korea; 2 Asan Medical Center, University of Ulsan College of Medicine, Dept. of Urology, Seoul, South Korea Introduction & Objectives: We assessed the cytotoxic effects of the gemcitabine in combination with oxaliplatin (GemOx) in prostate cancer cell lines and evaluated the efficacy and safety of this combination in patients with metastatic castration-resistant prostate cancer (CRPC) who failed docetaxel based chemotherapy. Material & Methods: Gemcitabine and oxaliplatin were preclinically tested for their cytotoxic activity (MTT assay) in a range of human prostate cancer cell lines (LNCaP, PC3 and DU145). The combined drug effects were evaluated using the Chou and Taladay analysis based on the medium-effect principle. Clinically, patients with CRPC who failed prior docetaxel-based chemotherapy were treated with gemcitabine 1,000 mg/m2 at fixed-dose rate (10 mg/m2 /min) and oxaliplatin 100 mg/m2 intravenously on day 1 every 2 weeks and prednisolone 5 mg orally twice daily. Unless disease progression or intolerable toxicity develops, treatment could be continued until 12 cycles. Primary endpoint was PSA response rate according to PCWG 1.0 criteria. Results: The IC50 of gemcitabine and oxaliplatin were, respectively, 1.23 μM and 1.06 μM for LNCaP cells; 2.06×105 μM and 5.66 μM for PC3 cells; and 9.92 μM and 9.06 μM for DU145 cells. The GemOx combination displayed synergistic effects in all 3 cell lines. In phase II study, 33 patients were accrued. The median age was 67 years (range 52–88) and the median dose of docetaxel exposure was 518 mg/m2 (IQR, 316–870). Seventy-seven percent of patients had progressive disease during the docetaxel chemotherapy and additional 7% had disease progression within 12 weeks after the completion of the last docetaxel chemotherapy. A total of 270 cycles administered with a median of 8 cycles per patient. PSA decline of ≥50% were observed in 55% (95% CI, 38–72) and radiologic partial responses were observed in 9 of 11 patients with measurable disease (81%). Out of 24 patients who were eligible for pain response assessment, 13 patients achieved pain response (54%). With a median FU duration of 20.5 months, the median time to PSA progression was 5.8 months (95% CI, 4.4– 7.2) and median time to composite progression (including PSA, RECIST, bone scan and pain) was 5.4 months (95% CI, 3.5–7.3). Peripheral neuropathy developed in 82% of patients but remained of grade 1 and 2 intensities. The most frequently observed grade 3 or 4 toxicities were neutropenia (9%), thrombocytopenia (9%), anemia (3%), and diarrhea (6%). Conclusions: GemOx combination displayed dramatic synergistic effects in prostate cancer cell lines. This combination is active and well tolerated in patients with CPRC after docetaxel failure and deserves further investigation in this setting (NCT 01487720).
P112 Treatment costs of advanced prostate cancer using existing LHRH agonists and potential savings associated with an innovative form of leuprorelin acetate as solid biodegradable implant D. Meani, K Walsh. Sandoz International GmbH, Sandoz Biopharmaceuticals, Holzkirchen, Germany Introduction & Objectives: Prostate cancer (PCa) is the second most common tumor in man: by 2020 incident cases are expected to increase by 43% reflecting largely ageing of the population. Luteinizing hormone-releasing hormone (LHRH) agonists represent one of the main cost factors in the management of patients with advanced PCa. In this analysis, treatment costs with alternative LHRH agonists were evaluated in terms of potential cost savings as a strategy to free-up resources for more expensive innovation.One LHRH agonist alternative is a ready-to-use subcutaneous formulation of leuprorelin acetate available as a solid biodegradable implant. This alternative was first launched in Germany in 2007 and is currently available in 20 countries worldwide with currently over 20 million patient-days of experience. In the comparator-controlled clinical studies, the leuprorelin implant was as effective as the traditional microsphere formulation for achieving successful testosterone suppression and normalization of PSA levels (Geiges G et al. Ther Adv Urol, 2013). Material & Methods: An economic model was developed to the highlight the potential cost savings of using the leuprorelin solid implant compared with the existing LHRH analogues, including those that need to be reconstituted. A hypothetical population of 1000 PCa patients was analyzed and apportioned amongst the hormonal medicines most commonly prescribed for treatment of advanced PCa, e.g. leuprorelin microspheres and goserelin. Patient costs were calculated with 3-month formulations of each treatment option based on a 1-year treatment period and were then compared to the leuprorelin solid implant formulation. Potential cost savings were calculated for 5 European countries (France, Germany, Italy, Spain and UK) (EU5) and Sweden. The analysis also estimated the time saved by using the ready-to-use implant formulation. Results: The cost analysis demonstrated that per 1000 patients, there is an average modeled savings of €562,000 per EU5 market and €813,000 for Sweden if patients were to utilize the leuprorelin solid implant pharmaceutical formulation. Preparation time saved for each market was calculated to be 177 hours using the ready-to-use implant. Conclusions: The use of leuprorelin solid implant could result in significant cost and time savings as compared with other existing LHRH analogues. These savings could be reallocated to novel high-cost drugs and to enhance patient outcomes. P113 Clinical management of prostate cancer with neuroendocrine status O.I. Apolikhin, A.V. Sivkov, N.G. Keshishev, E.Z. Rabinovich, G.A. Kovchenko, D.G. Sokov, S.A. Prohorov, L.M. Nikonova. Federal State Budget Research Institute of Urology, Innovative, Moscow, Russia Introduction & Objectives: Castration Resistant Prostate Cancer (CRPC) is a complex disease which treatment strategy is in serious disagreement among urologists around the world. This is due to the fact that the effectiveness of most conventional drugs (docetaxel, cabazitaxel, abiraterone acetate etc.) in the treatment of CRPC is not high. Treatment has great toxicity, response duration is short. Recently much attention has been paid to the study of Neuroendocrine Differentiation (NED) of the prostate gland and its role in the treatment of CRPC.The aim of our study is to in-
A B S T R A C T S / E U R O P E A N U R O L O G Y S U P P L E M E N T S 12 (2013) 123–180
lustrates the current pattern of MDT cooperation in Poland. Noninterventional study DIREG_L_02709 was sponsored by SanofiAventis. P111 Final results of phase II study of Gemcitabine-Oxalipaltin (GemOx) plus Prednisolone in patients with Castration-Resistant Prostate Cancer (CRPC) for whom Docetaxel-based chemotherapy failed Lee 1 ,
Ahn 1 ,
Choi 1 ,
Kim 1 ,
Hong 1 ,
J.-H. M. Y. S.-W. J.-L. I.-G. Jeong 2 , C. Song 2 , B.-S. Hong 2 , J.H. Hong 2 , H. Ahn 2 . 1 Asan Medical Center, University of Ulsan College of Medicine, Dept. of Oncology, Seoul, South Korea; 2 Asan Medical Center, University of Ulsan College of Medicine, Dept. of Urology, Seoul, South Korea Introduction & Objectives: We assessed the cytotoxic effects of the gemcitabine in combination with oxaliplatin (GemOx) in prostate cancer cell lines and evaluated the efficacy and safety of this combination in patients with metastatic castration-resistant prostate cancer (CRPC) who failed docetaxel based chemotherapy. Material & Methods: Gemcitabine and oxaliplatin were preclinically tested for their cytotoxic activity (MTT assay) in a range of human prostate cancer cell lines (LNCaP, PC3 and DU145). The combined drug effects were evaluated using the Chou and Taladay analysis based on the medium-effect principle. Clinically, patients with CRPC who failed prior docetaxel-based chemotherapy were treated with gemcitabine 1,000 mg/m2 at fixed-dose rate (10 mg/m2 /min) and oxaliplatin 100 mg/m2 intravenously on day 1 every 2 weeks and prednisolone 5 mg orally twice daily. Unless disease progression or intolerable toxicity develops, treatment could be continued until 12 cycles. Primary endpoint was PSA response rate according to PCWG 1.0 criteria. Results: The IC50 of gemcitabine and oxaliplatin were, respectively, 1.23 μM and 1.06 μM for LNCaP cells; 2.06×105 μM and 5.66 μM for PC3 cells; and 9.92 μM and 9.06 μM for DU145 cells. The GemOx combination displayed synergistic effects in all 3 cell lines. In phase II study, 33 patients were accrued. The median age was 67 years (range 52–88) and the median dose of docetaxel exposure was 518 mg/m2 (IQR, 316–870). Seventy-seven percent of patients had progressive disease during the docetaxel chemotherapy and additional 7% had disease progression within 12 weeks after the completion of the last docetaxel chemotherapy. A total of 270 cycles administered with a median of 8 cycles per patient. PSA decline of ≥50% were observed in 55% (95% CI, 38–72) and radiologic partial responses were observed in 9 of 11 patients with measurable disease (81%). Out of 24 patients who were eligible for pain response assessment, 13 patients achieved pain response (54%). With a median FU duration of 20.5 months, the median time to PSA progression was 5.8 months (95% CI, 4.4– 7.2) and median time to composite progression (including PSA, RECIST, bone scan and pain) was 5.4 months (95% CI, 3.5–7.3). Peripheral neuropathy developed in 82% of patients but remained of grade 1 and 2 intensities. The most frequently observed grade 3 or 4 toxicities were neutropenia (9%), thrombocytopenia (9%), anemia (3%), and diarrhea (6%). Conclusions: GemOx combination displayed dramatic synergistic effects in prostate cancer cell lines. This combination is active and well tolerated in patients with CPRC after docetaxel failure and deserves further investigation in this setting (NCT 01487720).
P112 Treatment costs of advanced prostate cancer using existing LHRH agonists and potential savings associated with an innovative form of leuprorelin acetate as solid biodegradable implant D. Meani, K Walsh. Sandoz International GmbH, Sandoz Biopharmaceuticals, Holzkirchen, Germany Introduction & Objectives: Prostate cancer (PCa) is the second most common tumor in man: by 2020 incident cases are expected to increase by 43% reflecting largely ageing of the population. Luteinizing hormone-releasing hormone (LHRH) agonists represent one of the main cost factors in the management of patients with advanced PCa. In this analysis, treatment costs with alternative LHRH agonists were evaluated in terms of potential cost savings as a strategy to free-up resources for more expensive innovation.One LHRH agonist alternative is a ready-to-use subcutaneous formulation of leuprorelin acetate available as a solid biodegradable implant. This alternative was first launched in Germany in 2007 and is currently available in 20 countries worldwide with currently over 20 million patient-days of experience. In the comparator-controlled clinical studies, the leuprorelin implant was as effective as the traditional microsphere formulation for achieving successful testosterone suppression and normalization of PSA levels (Geiges G et al. Ther Adv Urol, 2013). Material & Methods: An economic model was developed to the highlight the potential cost savings of using the leuprorelin solid implant compared with the existing LHRH analogues, including those that need to be reconstituted. A hypothetical population of 1000 PCa patients was analyzed and apportioned amongst the hormonal medicines most commonly prescribed for treatment of advanced PCa, e.g. leuprorelin microspheres and goserelin. Patient costs were calculated with 3-month formulations of each treatment option based on a 1-year treatment period and were then compared to the leuprorelin solid implant formulation. Potential cost savings were calculated for 5 European countries (France, Germany, Italy, Spain and UK) (EU5) and Sweden. The analysis also estimated the time saved by using the ready-to-use implant formulation. Results: The cost analysis demonstrated that per 1000 patients, there is an average modeled savings of €562,000 per EU5 market and €813,000 for Sweden if patients were to utilize the leuprorelin solid implant pharmaceutical formulation. Preparation time saved for each market was calculated to be 177 hours using the ready-to-use implant. Conclusions: The use of leuprorelin solid implant could result in significant cost and time savings as compared with other existing LHRH analogues. These savings could be reallocated to novel high-cost drugs and to enhance patient outcomes. P113 Clinical management of prostate cancer with neuroendocrine status O.I. Apolikhin, A.V. Sivkov, N.G. Keshishev, E.Z. Rabinovich, G.A. Kovchenko, D.G. Sokov, S.A. Prohorov, L.M. Nikonova. Federal State Budget Research Institute of Urology, Innovative, Moscow, Russia Introduction & Objectives: Castration Resistant Prostate Cancer (CRPC) is a complex disease which treatment strategy is in serious disagreement among urologists around the world. This is due to the fact that the effectiveness of most conventional drugs (docetaxel, cabazitaxel, abiraterone acetate etc.) in the treatment of CRPC is not high. Treatment has great toxicity, response duration is short. Recently much attention has been paid to the study of Neuroendocrine Differentiation (NED) of the prostate gland and its role in the treatment of CRPC.The aim of our study is to in-