title: Randomized phase III clinical trial comparing the combination of capecitabine and oxaliplatin (CAPOX) with the combination of 5-fluorouracil, leucovorin and oxaliplatin (modified FOLFOX6) as adjuvant therapy in patients with operated high-risk stage II or stage III colorectal cancer.
abstract: BACKGROUND
  The aim of the trial was to compare two active adjuvant chemotherapy regimens in patients with early stage colorectal cancer (CRC).
  
  
  METHODS
  Patients were assigned to oxaliplatin, leucovorin and 5-FU for 12 cycles (group A, FOLFOX6) or oxaliplatin and capecitabine for eight cycles (group B, CAPOX). Primary endpoint was disease-free survival (DFS). Tumors were classified as mismatch repair proficient (pMMR) or deficient (dMMR) according to MLH1, PMS2, MSH2 and MSH6 protein expression. KRAS exon two and BRAF V600E mutational status were also assessed.
  
  
  RESULTS
  Between 2005 and 2008, 441 patients were enrolled, with 408 patients being eligible. After a median follow-up of 74.7 months, 3-year DFS was 79.8 % (95 % CI 76.5-83.4) in the FOLFOX group and 79.5 % (95 % CI 75.9-83.1) in the CAPOX group (p = 0.78). Three-year OS was 87.2 % (95 % CI 84.1-91.1) in the FOLFOX and 86.9 % (95 % CI 83.4-89.9) in the CAPOX group (p = 0.84). Among 306 available tumors, 11.0 % were dMMR, 34.0 % KRAS mutant and 4.9 % BRAF mutant. Multivariate analysis showed that primary site in the left colon, earlier TNM stage and the presence of anemia at diagnosis were associated with better DFS and overall survival (OS), while grade one-two tumors were associated with better OS. Finally, a statistically significant interaction was detected between the primary site and MMR status (p = 0.010), while KRAS mutated tumors were associated with shorter DFS. However, the sample was too small for safe conclusions.
  
  
  CONCLUSIONS
  No significant differences were observed in the efficacy of FOLFOX versus CAPOX as adjuvant treatment in high-risk stage II or stage III CRC patients, but definitive conclusions cannot be drawn because of the small sample size.
  
  
  BACKGROUND
  ANZCTR 12610000509066 . Date of Registration: June 21, 2010.
authors.affiliation: Oncology Section, Second Department of Internal Medicine, "Hippokration" Hospital, Athens, 11527, Greece. pectasid@otenet.gr.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Pectasides
authors.affiliation: Department of Medical Oncology, "Papageorgiou" Hospital, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece. karavasv@auth.gr.
authors.forename: Vasilios
authors.initials: V
authors.lastname: Karavasilis
authors.affiliation: Oncology Section, Second Department of Internal Medicine, "Hippokration" Hospital, Athens, 11527, Greece. georgexoinis@gmail.com.
authors.forename: George
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authors.lastname: Papaxoinis
authors.affiliation: Section of Biostatistics, Hellenic Cooperative Oncology Group, Data Office, Athens, Greece. g_gourgioti@hecog.ondsl.gr.
authors.forename: Georgia
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authors.lastname: Gourgioti
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authors.affiliation: Department of Pathology, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece. graptou@auth.gr.
authors.forename: Georgia
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authors.affiliation: Department of Pathology, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece. evrettou@med.auth.gr.
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authors.lastname: Vrettou
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authors.forename: Joseph
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authors.affiliation: Third Department of Medical Oncology, "Agii Anargiri" Cancer Hospital, Athens, Greece. epsam@otenet.gr.
authors.forename: Epaminontas
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authors.lastname: Samantas
authors.affiliation: First Propaedeutic Department of Surgery, "AHEPA" Hospital, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece. basdanis@med.auth.gr.
authors.forename: George
authors.initials: G
authors.lastname: Basdanis
authors.affiliation: Department of Medical Oncology, "Hippokration" Hospital, Athens, Greece. p.papakostas@gmail.com.
authors.forename: Pavlos
authors.initials: P
authors.lastname: Papakostas
authors.affiliation: First Department of Medical Oncology, "Metropolitan" Hospital, Piraeus, Greece. dimmp@otenet.gr.
authors.forename: Dimitrios
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authors.lastname: Bafaloukos
authors.affiliation: Department of Pathology, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece. vkotoula@auth.gr.|Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece. vkotoula@auth.gr.
authors.forename: Vassiliki
authors.initials: V
authors.lastname: Kotoula
authors.affiliation: Division of Oncology, Department of Medicine, University Hospital, University of Patras Medical School, Patras, Greece. kalofonos@upatras.gr.
authors.forename: Haralambos P
authors.initials: HP
authors.lastname: Kalofonos
authors.affiliation: Department of Pathology, University Hospital, University of Patras Medical School, Patras, Greece. cdscopa@med.upatras.gr.
authors.forename: Chrisoula D
authors.initials: CD
authors.lastname: Scopa
authors.affiliation: Department of Medical Oncology, Ioannina University Hospital, Ioannina, Greece. gpenther@otenet.gr.
authors.forename: George
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authors.lastname: Pentheroudakis
authors.affiliation: Department of Medical Oncology, "Papageorgiou" Hospital, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece. fountzil@auth.gr.|Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece. fountzil@auth.gr.
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mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D000069287:Capecitabine / Q000008:administration & dosage*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology / Q000601:surgery; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage*; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage*; D008297:Male; D053842:Microsatellite Instability / Q000187:drug effects; D008875:Middle Aged; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage*; D000077150:Oxaliplatin; D011518:Proto-Oncogene Proteins / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins / Q000235:genetics
chemical_list: C117307:KRAS protein, human; D009944:Organoplatinum Compounds; D011518:Proto-Oncogene Proteins; D000077150:Oxaliplatin; D000069287:Capecitabine; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D002955:Leucovorin; D005472:Fluorouracil