1. Results of methotrexate-etoposide-ifosfamide based regimen (M-EI) in osteosarcoma patients included in the French OS2006/sarcome-09 study
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Cécile Verite-Goulard, Nadir Cheurfa, Laurence Brugières, Sophie Piperno-Neumann, Laure Saumet, Nathalie Gaspar, Nadège Corradini, Perrine Marec-Berard, Hervé Brisse, Marie-Cécile Le Deley, Françoise Rédini, Claudine Schmitt, Gsf-Geto (Groupe Sarcome Français), Jessy Delaye, Hélène Pacquement, Emmanuelle Bompas, Marie-Pierre Castex, Jean-Claude Gentet, Bob-Valéry Occean, Natacha Entz-Werle, Cyril Lervat, Eric Mascard, Marie-Dominique Tabone, Corine Bouvier, Sfce, Antoine Italiano, Département de cancérologie de l'enfant et de l'adolescent [Gustave Roussy], Institut Gustave Roussy (IGR), Service de biostatistique et d'épidémiologie (SBE), Direction de la recherche clinique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Département d'oncologie pédiatrique [Institut Curie, Paris], Institut Curie [Paris], Département d'oncologie médicale [Saint Herblain], Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER, Département de pathologie [CHU La Timone, Marseille], Hôpital de la Timone [CHU - APHM] (TIMONE), Service de l'Imagerie [Institut Curie, Paris], Paris-Sciences-et-Lettres Research University [Paris], Département d'oncologie pédiatrique [CHU Toulouse], CHU Toulouse [Toulouse], Département d'Oncologie Pédiatrique [CHU Nantes], Hôpital Mère-Enfant, CHU de Nantes, UNICANCER [Paris], Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Département d'Oncologie Pédiatrique [CHU Hautepierre, Strasbourg], Hôpital de Hautepierre [Strasbourg], Pédiatrie et oncologie pédiatrique [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Département d'oncologie médicale, Institut Bergonié [Bordeaux], Unité d'oncologie pédiatrique [Centre Oscar Lambret, Lille], Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER-Université Lille Nord de France (COMUE)-UNICANCER, Département d'oncologie pédiatrique [Centre Léon Bérard, Lyon], Centre Léon Bérard [Lyon], Service de chirurgie orthopédique et traumatologie pédiatrique [CHU Necker ], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Physiopathologie des Adaptations Nutritionnelles (PhAN), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Département d'oncologie pédiatrique [Hôpital A. de Villeneuve, Montpellier], Hôpital Arnaud de Villeneuve [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service d'Hématologie et d'Oncologie Pédiatrique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Département d'oncologie pédiatrique [CHU Bordeaux], Hôpital des Enfants - Groupe hospitalier Pellegrin - CHU de Bordeaux, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Lille Nord de France (COMUE)-UNICANCER, Département d'Oncologie Médicale [Institut Curie, Paris], French National Cancer Institute (INCa) (INCA RC004 and PHRC-K13-041), NOVARTIS, Chugai, Ligue Nationale contre le Cancer, Fédération Enfants et Santé, Société Française des Cancers et Leucémies de l’Enfant., the SFCE (Société Française des Cancers de l’Enfant et l’adolescent), GSF-GETO (Groupe Sarcome Français), the UNICANCER sarcoma group., Sercice Hématologie, immunologie et oncologie pédiatrique [CHU Toulouse], Pôle Enfants [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Lille-UNICANCER-Université de Lille-UNICANCER, Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN), Université de Lille-UNICANCER, and maurice, sandrine
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Male ,0301 basic medicine ,Cancer Research ,medicine.medical_treatment ,Kaplan-Meier Estimate ,Zoledronic Acid ,0302 clinical medicine ,Antineoplastic Combined Chemotherapy Protocols ,Medicine ,Young adult ,Child ,Etoposide ,[SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system ,Osteosarcoma ,Ifosfamide ,Diphosphonates ,Imidazoles ,Combined Modality Therapy ,3. Good health ,Oncology ,[SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system ,Child, Preschool ,030220 oncology & carcinogenesis ,Female ,France ,medicine.drug ,Adult ,medicine.medical_specialty ,Neutropenia ,Adolescent ,Bone Neoplasms ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Young Adult ,03 medical and health sciences ,[SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics ,[SDV.CAN] Life Sciences [q-bio]/Cancer ,Humans ,Chemotherapy ,[SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics ,business.industry ,medicine.disease ,Surgery ,Regimen ,030104 developmental biology ,Methotrexate ,Doxorubicin ,Cisplatin ,business - Abstract
Background In most countries, reference chemotherapy for osteosarcoma is MAP regimen (M = high-dose methotrexate, AP = doxorubicin-cisplatinum). In France, the standard preoperative chemotherapy for children/adolescents combines M and etoposide-ifosfamide (EI), based on the OS94-trial. We report the safety and efficacy results of patients ≤25 years treated with preoperative M-EI regimen enroled in the French OS2006-study, between 2007 and 2014. Methods Treatment comprised preoperative chemotherapy with the 7 M-courses and 2 EI-courses, then surgery and postoperative chemotherapy assigned by risk's groups: standard-risk (good histological response without metastases) received 12 M-courses, 3 EI-courses; high-risk (poor histologic response, initial metastases or unresectable primary) received 5 M-courses alternated with 5 AP-courses. 253 patients were randomised to receive (n = 128) or not (n = 125) zoledronate. Results 409/522 patients enroled in the OS2006 study who received preoperative M-EI were analysed. Median age was 14.3 years (4.7–24.5), with 55 patients aged 18–25 years. Primary tumour location was limb in 383 patients (94%) and 85 (21%) presented metastases. Median chemotherapy duration was 37.4 weeks. 381 (96%) patients underwent surgery, 258 patients (65%) had a good histologic response. 187/324 patients (58%) with localised disease did not receive doxorubicin nor cisplatinum. Toxicity was evaluated in the randomised study: most patients experienced ≥1 severe toxicity (grade IV haematological or grade III/IV extra-haematological). Median follow-up was 4.8 years, and 168 patients had events. Five-year event-free survival was 56% (95% CI, 51–62%) and overall survival 71% (66–76%). Conclusion M-EI regimen/strategy was feasible for patient aged ≤25 years with survival rates are comparable to those obtained with MAP regimen.
- Published
- 2017
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