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

BMC Cancer

Research Article

George Pentheroudakis¹  Pavlos Papakostas²  Vasilios Karavasilis³  George Fountzilas⁴  Eleni Vrettou⁵  Georgia Raptou⁵  Vassiliki Kotoula⁶  Chrisoula D. Scopa⁷  Haralambos P. Kalofonos⁸  Thomas Makatsoris⁸  Dimitrios Bafaloukos⁹  George Basdanis^1,10  Dimitrios Pectasides^1,11  George Papaxoinis^1,11  Georgia Gourgioti^1,12  Epaminontas Samantas^1,13  Joseph Sgouros^1,13 

[1] Department of Medical Oncology, Ioannina University Hospital, Ioannina, Greece;Department of Medical Oncology, “Hippokration” Hospital, Athens, Greece;Department of Medical Oncology, “Papageorgiou” Hospital, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece;Department of Medical Oncology, “Papageorgiou” Hospital, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece;Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece;Department of Pathology, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece;Department of Pathology, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece;Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece;Department of Pathology, University Hospital, University of Patras Medical School, Patras, Greece;Division of Oncology, Department of Medicine, University Hospital, University of Patras Medical School, Patras, Greece;First Department of Medical Oncology, “Metropolitan” Hospital, Piraeus, Greece;First Propaedeutic Department of Surgery, “AHEPA” Hospital, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece;Oncology Section, Second Department of Internal Medicine, “Hippokration” Hospital, 11527, Athens, Greece;Section of Biostatistics, Hellenic Cooperative Oncology Group, Data Office, Athens, Greece;Third Department of Medical Oncology, “Agii Anargiri” Cancer Hospital, Athens, Greece;

关键词: Colorectal cancer;    Adjuvant chemotherapy;    Modified FOLFOX6;    Capecitabine;    Oxaliplatin;    Prognosis;    KRAS;    Microsatellite instability;   

DOI  :  10.1186/s12885-015-1406-7

 received in 2014-07-06, accepted in 2015-04-29,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundThe aim of the trial was to compare two active adjuvant chemotherapy regimens in patients with early stage colorectal cancer (CRC).MethodsPatients 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.ResultsBetween 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.ConclusionsNo 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.Trial registrationANZCTR 12610000509066. Date of Registration: June 21, 2010.

【 授权许可】

CC BY   
© Pectasides et al.; licensee BioMed Central. 2015