1. Perioperative FOLFOX 4 Versus FOLFOX 4 Plus Cetuximab Versus Immediate Surgery for High-Risk Stage II and III Colon Cancers
- Author
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Karoui, M., Rullier, A., Piessen, G., Legoux, J., Barbier, E., De Chaisemartin, C., Lecaille, C., Bouché, O., Ammarguellat, H., Brunetti, F., Prudhomme, M., Regimbeau, J., Glehen, O., Lievre, A., Portier, G., Hartwig, J., Goujon, G., ROMAIN, B., Lepage, C., Taïeb, J., Service de chirurgie digestive et viscérale [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Department of Digestive and Oncological Surgery [Lille], Hôpital Claude Huriez [Lille], CHU Lille-CHU Lille-Université de Lille, La Source Hospital-CHR, Université Bourgogne Franche-Comté [COMUE] (UBFC), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Service d’Hémato-oncologie [Polyclinique Bordeaux Nord Aquitaine], Polyclinique Bordeaux Nord Aquitaine, Département d'oncologie médicale (CHU Robert Debré, Reims), Centre Hospitalier Universitaire de Reims (CHU Reims), Service de chirurgie digestive (Centre Hospitalier de Beauvais), Centre Hospitalier de Beauvais, Service de Chirurgie Digestive Hépato-Billiaire [Henri Mondor], Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Chirurgie digestive [CHU Amiens], CHU Amiens-Picardie, Ciblage thérapeutique en Oncologie (EA3738), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Service d'hépato-gastro-entérologie [Rennes] = Gastroenterology [Rennes], CHU Pontchaillou [Rennes], Service de Chirurgie digestive, CHU Purpan, Université Paul Sabatier, Toulouse, France, Clinique de l'Infirmerie Protestante, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de chirurgie digestive [Strasbourg-Hautepierre], Hôpital de Hautepierre [Strasbourg], Equipe EPICAD (LNC - U1231), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Service d'Hépato-Gastro-Entérologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Polyclinique Bordeaux Nord Aquitaine (PBNA), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'hépato-gastro-entérologie [Rennes], Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes]
- Subjects
MESH: Antineoplastic Combinated Chemotherapy Protocols / therapeutic use ,Cetuximab / therapeutic use ,Colectcomy ,Colonic Neoplasms / drug therapy ,MESH: Colonic Neoplasms / surgery ,Neoadjuvant Therapy ,Tomography, X-Ray, Computed ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,[SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery ,[SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences ,digestive system diseases - Abstract
International audience; Perioperative chemotherapy has proven valuable in several tumors, but not in colon cancer (CC).Objective: The aim of this study was to evaluate the efficacy and safety of perioperative chemotherapy in patients with locally advanced nonmetastatic CC.Methods: This is a French multicenter randomized phase II trial in patients with resectable high-risk T3, T4, and/or N2 CC on baseline computed tomography (CT) scan. Patients were randomized to receive either 6 months of adjuvant FOLFOX after colectomy (control) or perioperative FOLFOX for 4 cycles before surgery and 8 cycles after (FOLFOX peri-op). In RAS wild-type patients, a third arm testing perioperative FOLFOX-cetuximab was added. Tumor Regression Grade (TRG1) of Ryan et al was the primary endpoint. Secondary endpoints were toxicity, perioperative morbidity, and quality of surgery.Results: A total of 120 patients were enrolled. At interim analysis, the FOLFOX-cetuximab arm was stopped (lack of efficacy). The remaining 104 patients (control, n = 52; FOLFOX preop n = 52) represented our intention-to-treat population. In the FOLFOX perioperative group, 96% received the scheduled 4 cycles before surgery. R0 resection and complete mesocolic excision rate were 94% and 93%, respectively. Overall mortality and morbidity rates were similar in both groups. Perioperative FOLFOX chemotherapy did not improve major pathological response rate (TRG1 = 8%) but was associated with a significant pathological regression (TRG1-2 = 44% vs 8%, P < 0.001) and a trend to tumor downstaging as compared to the control group. CT scan criteria were associated with a 33% rate of overstaging in control group.Conclusions: Perioperative FOLFOX for locally advanced resectable CC is feasible with an acceptable tolerability but is not associated with an increased major pathological response rate as expected. However, perioperative FOLFOX induces pathological regression and downstaging. Better preoperative staging tools are needed to decrease the risk of overtreating patients.
- Published
- 2020
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