Original Article
Copyright ©2010 Baishideng. All rights reserved.
World J Gastroenterol. Jul 7, 2010; 16(25): 3133-3143
Published online Jul 7, 2010. doi: 10.3748/wjg.v16.i25.3133
Cetuximab plus FOLFOX6 or FOLFIRI in metastatic colorectal cancer: CECOG trial
Janja Ocvirk, Thomas Brodowicz, Fritz Wrba, Tudor E Ciuleanu, Galina Kurteva, Semir Beslija, Ivan Koza, Zsuzsanna Pápai, Diethelm Messinger, Ugur Yilmaz, Zsolt Faluhelyi, Suayib Yalcin, Demetris Papamichael, Miklós Wenczl, Zrinka Mrsic-Krmpotic, Einat Shacham-Shmueli, Damir Vrbanec, Regina Esser, Werner Scheithauer, Christoph C Zielinski
Janja Ocvirk, Institute of Oncology, 1000 Ljubljana, Slovenia
Thomas Brodowicz, Werner Scheithauer, Christoph C Zielinski, Clinical Division of Oncology, Department of Medicine I, Medical University of Vienna, 1090 Vienna, Austria
Fritz Wrba, Clinical Institute of Pathology, Medical University of Vienna, 1090 Vienna, Austria
Tudor E Ciuleanu, Institutul Oncologic Cluj, 400015 Cluj-Napoca, Romania
Galina Kurteva, Department of Oncology, National Specialized Hospital of Active Treatment in Oncology, 1754 Sofia, Bulgaria
Semir Beslija, Institute of Oncology, Clinical Center of Sarajevo University, 71000 Sarajevo, Bosnia-Herzegovina
Ivan Koza, Department of Oncology, National Cancer Institute, 83310 Bratislava, Slovak Republic
Zsuzsanna Pápai, AEK Onkologiai Osztaly, 1122 Budapest, Hungary
Diethelm Messinger, Biometrics, IST GmbH, 68219 Mannheim, Germany
Ugur Yilmaz, Department of Gastroenterology, 9 Eylül University Medical Faculty, 35340 Izmir, Turkey
Zsolt Faluhelyi, Oncology Department, Veszprém County Hospital, 8200 Veszprém, Hungary
Suayib Yalcin, Institute of Oncology, Ankara Hacettepe University, 06100 Ankara, Turkey
Demetris Papamichael, Department of Medical Oncology, Bank of Cyprus Oncology Center, 2006 Nicosia, Cyprus
Miklós Wenczl, Department of Oncoradiology, Markusovszky Teaching Hospital, 9700, Szombathely, Hungary
Zrinka Mrsic-Krmpotic, Department of Medical Oncology, University Hospital for Tumors, 10000 Zagreb, Croatia
Einat Shacham-Shmueli, Oncology Division, Tel-Aviv Souraski Medical Center, Tel Aviv 64239, Israel
Damir Vrbanec, KBC Rebro, Oncology Department, 10000 Zagreb, Croatia
Regina Esser, Merck KGaA, D64293 Darmstadt, Germany
Author contributions: Ocvirk J, Brodowicz T, Ciuleanu TE, Kurteva G, Beslija S, Koza I, Pápai Z, Yilmaz U, Faluhelyi Z, Yalcin S, Papamichael D, Wenczl M, Mrsic-Krmpotic Z, Shacham-Shmueli E, Vrbanec D, Scheithauer W and Zielinski CC are in charge of different patients and materials to the study; Brodowicz T, Messinger D, Esser R and Zielinski CC were involved in the study design; Brodowicz T, Wrba F, Messinger D, Esser R and Zielinski CC performed the research including the KRAS tumor mutational analysis; Messinger D co-ordinated the data analysis; Brodowicz T, Messinger D and Esser R were involved in the manuscript writing and all authors gave final approval to the manuscript submission.
Correspondence to: Dr. Thomas Brodowicz, MD, Clinical Division of Oncology, Department of Medicine I, Medical University of Vienna, 1090 Vienna, Austria. thomas.brodowicz@meduniwien.ac.at
Telephone: +43-1-4097725 Fax: +43-1-4097726
Received: February 15, 2010
Revised: April 15, 2010
Accepted: April 22, 2010
Published online: July 7, 2010
Abstract

AIM: To investigate efficacy and safety of cetuximab combined with two chemotherapy regimens in patients with unresectable metastatic colorectal cancer (mCRC).

METHODS: Randomized patients received cetuximab with 5-fluorouracil (5-FU), folinic acid (FA) and oxaliplatin (FOLFOX) 6 (arm A, n = 74) or 5-FU, FA and irinotecan (FOLFIRI) (arm B, n = 77). KRAS mutation status was determined retrospectively in a subset of tumors (n = 117).

RESULTS: No significant difference was found between treatment arms A and B in the progression-free survival (PFS) rate at 9 mo, 45% vs 34%; median PFS, 8.6 mo vs 8.3 mo [hazard ratio (HR) = 1.06]; overall response rate (ORR) 43% vs 45% [odds ratio (OR) = 0.93] and median overall survival (OS), 17.4 mo vs 18.9 mo (HR = 0.98). Patients with KRAS wild-type tumors demonstrated improved PFS (HR = 0.55, P = 0.0051), OS, (HR = 0.62, P = 0.0296) and ORR (53% vs 36%) and in arm A, improved PFS (HR = 0.49, P = 0.0196), OS (HR = 0.48, P = 0.0201) and ORR (56% vs 30%), compared with patients with KRAS mutated tumors. In arm B no significant differences were found in efficacy by KRAS mutation status. Treatment in arms A and B was generally well tolerated.

CONCLUSION: This study confirms that combinations of cetuximab with FOLFOX6 or FOLFIRI are effective and significantly improve clinical outcome in KRAS wild-type compared with KRAS mutated mCRC.

Keywords: Cetuximab; 5-fluorouracil folinic acid and oxaliplatin; 5-fluorouracil folinic acid and irinotecan; KRAS; Metastatic colorectal cancer