title: Capecitabine plus oxaliplatin (XELOX) versus 5-fluorouracil/leucovorin plus oxaliplatin (FOLFOX-6) as first-line treatment for metastatic colorectal cancer.
abstract: A regimen consisting of 5-fluorouracil/leucovorin plus oxaliplatin (FOLFOX-6) is widely used in France in the first-line treatment of metastatic colorectal cancer (MCRC). The aim of our study was to demonstrate the non-inferiority of capecitabine plus oxaliplatin (XELOX) versus FOLFOX-6 for this indication. Patients were randomly assigned to receive XELOX or FOLFOX-6 for 6 months. The primary endpoint was overall response rate (ORR) in the per-protocol (PP) population; however, progression-free and overall survival (OS), time to response and response duration were also assessed. A total of 306 patients were enrolled (XELOX n = 156; FOLFOX-6 n = 150). ORR was 42 and 46% with XELOX and FOLFOX-6, respectively, in the PP population. The difference between groups was 4.7%; the upper limit of the unilateral 95% confidence interval (14.4%) was below the non-inferiority margin of 15%. In the intent-to-treat population, median progression-free survival was 8.8 months with XELOX and 9.3 months with FOLFOX-6, and median OS was 19.9 and 20.5 months, respectively. XELOX patients had significantly more grade 3/4 thrombocytopenia (12% vs. 5%) and diarrhoea (14% vs. 7%), but significantly less grade 3/4 neutropenia (5% vs. 47%), febrile neutropenia (0% vs. 6%) and neuropathy (11% vs. 26%) than FOLFOX-6 patients. We conclude that XELOX is non-inferior in terms of efficacy to FOLFOX-6 in the first-line treatment of MCRC, but has a different toxicity profile.
authors.affiliation: Department of Medicine, Gustave Roussy Institute, Villejuif, France. ducreux@igr.fr
authors.forename: Michel
authors.initials: M
authors.lastname: Ducreux
authors.forename: Jaafar
authors.initials: J
authors.lastname: Bennouna
authors.forename: Mohamed
authors.initials: M
authors.lastname: Hebbar
authors.forename: Marc
authors.initials: M
authors.lastname: Ychou
authors.forename: Gérard
authors.initials: G
authors.lastname: Lledo
authors.forename: Thierry
authors.initials: T
authors.lastname: Conroy
authors.forename: Antoine
authors.initials: A
authors.lastname: Adenis
authors.forename: Roger
authors.initials: R
authors.lastname: Faroux
authors.forename: Christine
authors.initials: C
authors.lastname: Rebischung
authors.forename: Loic
authors.initials: L
authors.lastname: Bergougnoux
authors.forename: Leila
authors.initials: L
authors.lastname: Kockler
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Douillard
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000069287:Capecitabine; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000473:pathology; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage*; D000077150:Oxaliplatin; D012004:Rectal Neoplasms / Q000188:drug therapy / Q000473:pathology; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000069287:Capecitabine; D002955:Leucovorin; D005472:Fluorouracil