F Selle1, S Wittnebel2, P Biron3, G Gravis4, G Roubaud5, B N Bui5, R Delva6, J O Bay7, A Fléchon3, L Geoffrois8, A Caty9, D G Soares10, T de Revel11, K Fizazi2, J Gligorov12, J M Micléa13, C Dubot10, S Provent10, I Temby10, M Gaulet14, E Horn15, I Brindel16, J P Lotz12. 1. Department of Medical Oncology and Cellular Therapy, APREC (Alliance Pour la Recherche En Cancérologie), Hôpital Tenon (Hôpitaux Universitaires de l'Est-Parisien, AP-HP), Paris Sorbonne Universités, Université Pierre et Marie Curie (UPMC Univ Paris 06), Paris frederic.selle@tnn.aphp.fr. 2. Department of Medicine, Institut Gustave Roussy, Villejuif. 3. Department of Medical Oncology, Centre Léon Bérard, Lyon. 4. Department of Medical Oncology, Institut Paoli Calmette, Marseille. 5. Department of Medicine, Institut Bergonié, Bordeaux. 6. Department of Chemotherapy, Centre Paul Papin, Angers. 7. Department of Medicine, Centre Hospitalier Universitaire, Clermont-Ferrand. 8. Department of Medicine, Centre Alexis Vautrin, Nancy. 9. Department of Medicine, Centre Oscar Lambret, Lille. 10. Department of Medical Oncology and Cellular Therapy, APREC (Alliance Pour la Recherche En Cancérologie), Hôpital Tenon (Hôpitaux Universitaires de l'Est-Parisien, AP-HP), Paris. 11. Department of Hematology, Hôpital D'Instruction des Armées Percy, Clamart. 12. Department of Medical Oncology and Cellular Therapy, APREC (Alliance Pour la Recherche En Cancérologie), Hôpital Tenon (Hôpitaux Universitaires de l'Est-Parisien, AP-HP), Paris Sorbonne Universités, Université Pierre et Marie Curie (UPMC Univ Paris 06), Paris. 13. Cytapheresis and Cell Therapy Unit, Hôpital St Louis (AP-HP), Paris. 14. Statistic, 3ES-Cegedim Strategic Data, Boulogne, France. 15. Department of Internal Medicine, Brown University, Rhode Island Hospital, Providence, Rhode Island, USA. 16. Department of Clinical Research, Hôpital St Louis (AP-HP), Paris, France.
Abstract
BACKGROUND: High-dose chemotherapy (HDCT) is an effective salvage treatment of germ-cell tumors (GCTs) patients. In the first salvage setting, 30%-70% of patients may achieve durable remissions. Even when HDCT is administered as subsequent salvage treatment, up to 20% of patients may still be definitively cured. However, patients with refractory/relapsed disease still have a very poor long-term prognosis, requiring earlier intervention of HDCT. PATIENTS AND METHODS: This phase II trial was addressed to nonrefractory patients failing Cisplatin-based chemotherapy. Inclusion criteria included seminomatous GCT in relapse after two lines of chemotherapy, nonseminomatous GCT in relapse after first or second lines, partial remission after first line, primary mediastinal GCT in first relapse. Patients received two cycles combining Epirubicin and Paclitaxel (Epi-Tax), followed by three consecutive HDCT, one using a Paclitaxel/Thiotepa (Thio-Tax) association and two using the 5-day Ifosfamide-Carboplatin-Etoposide regimen. The main objective was to determine the complete response rate. RESULTS: Forty-five patients were included between September 2004 and December 2007: 44 received the first HDCT cycle, 39 two HDCT cycles, 29 could receive the whole protocol. Sixteen patients did not receive the entire protocol, including eight (17.7%) for toxic side-effects. Two patients (4.4%) died of toxicities, and 17 (37.7%) of disease progression. With a median follow-up time of 26 months (range, 4-51), the final overall response rate was 48.8% (including a complete response rate of 15.5% and a partial response/negative serum markers rate of 26.6%) in an intent-to-treat analysis. The median progression-free survival (PFS) and overall survival (OS) times were 22 months [95% confidence interval (CI) 2-not reached] and 32 months (95% CI 4-49), respectively. The 2-year PFS was a plateau setup at 50% (95% CI 32-67) and the 2-year OS was 66% (95% CI 44-81). CONCLUSION: The TAXIF II protocol was effective in nonrefractory GCT patients failing Cisplatin-based chemotherapy. The toxic death rate remained acceptable in the field of HDCT regimens. TRIAL REGISTRATION NUMBER: NCT00231582.
BACKGROUND: High-dose chemotherapy (HDCT) is an effective salvage treatment of germ-cell tumors (GCTs) patients. In the first salvage setting, 30%-70% of patients may achieve durable remissions. Even when HDCT is administered as subsequent salvage treatment, up to 20% of patients may still be definitively cured. However, patients with refractory/relapsed disease still have a very poor long-term prognosis, requiring earlier intervention of HDCT. PATIENTS AND METHODS: This phase II trial was addressed to nonrefractory patients failing Cisplatin-based chemotherapy. Inclusion criteria included seminomatous GCT in relapse after two lines of chemotherapy, nonseminomatous GCT in relapse after first or second lines, partial remission after first line, primary mediastinal GCT in first relapse. Patients received two cycles combining Epirubicin and Paclitaxel (Epi-Tax), followed by three consecutive HDCT, one using a Paclitaxel/Thiotepa (Thio-Tax) association and two using the 5-day Ifosfamide-Carboplatin-Etoposide regimen. The main objective was to determine the complete response rate. RESULTS: Forty-five patients were included between September 2004 and December 2007: 44 received the first HDCT cycle, 39 two HDCT cycles, 29 could receive the whole protocol. Sixteen patients did not receive the entire protocol, including eight (17.7%) for toxic side-effects. Two patients (4.4%) died of toxicities, and 17 (37.7%) of disease progression. With a median follow-up time of 26 months (range, 4-51), the final overall response rate was 48.8% (including a complete response rate of 15.5% and a partial response/negative serum markers rate of 26.6%) in an intent-to-treat analysis. The median progression-free survival (PFS) and overall survival (OS) times were 22 months [95% confidence interval (CI) 2-not reached] and 32 months (95% CI 4-49), respectively. The 2-year PFS was a plateau setup at 50% (95% CI 32-67) and the 2-year OS was 66% (95% CI 44-81). CONCLUSION: The TAXIF II protocol was effective in nonrefractory GCT patients failing Cisplatin-based chemotherapy. The toxic death rate remained acceptable in the field of HDCT regimens. TRIAL REGISTRATION NUMBER: NCT00231582.
Authors: Y Nieto; S-M Tu; R Bassett; R B Jones; A M Gulbis; N Tannir; A Kingham; C Ledesma; K Margolin; L Holmberg; R Champlin; L Pagliaro Journal: Ann Oncol Date: 2015-07-21 Impact factor: 32.976
Authors: F Selle; J Gligorov; S Richard; A Khalil; I Alexandre; D Avenin; S Provent; D G Soares; J P Lotz Journal: Braz J Med Biol Res Date: 2014-11-04 Impact factor: 2.590