Annals of Oncology Advance Access originally published online on June 23, 2009
Annals of Oncology 2009 20(10):1667-1673; doi:10.1093/annonc/mdp069
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gastrointestinal tumors |
Cetuximab plus cisplatin–5-fluorouracil versus cisplatin–5-fluorouracil alone in first-line metastatic squamous cell carcinoma of the esophagus: a randomized phase II study of the Arbeitsgemeinschaft Internistische Onkologie
1 Third Department of Internal Medicine (Hematology/Medical Oncology)
2 Department of Medical Statistics and Epidemiology, Technical University of Munich, Munich
3 Department of Medicine, Hospital Bremen-Ost, Bremen
4 Department of Hematology and Oncology, Krankenhaus Nordwest, Frankfurt am Main
5 Department of Medicine III, University Hospital Mannheim, Mannheim
6 Department of Hematology and Oncology, Charite, Medical University, Berlin
7 First Medical Department, Johannes Gutenberg-University Mainz, Mainz
8 Charite, Campus Benjamin Franklin, Berlin
9 Department of Internal Medicine IV, Martin-Luther-University, Halle
10 Department of Gastroenterology, Hepatology and Endocrinology, Center for Internal Medicine, Medical School of Hannover, Hannover
11 Oncological main focus-practice Leer-Emden
12 Munich Center for Clinical Studies, Munich
13 Department of Pathology, Technical University of Munich, Munich
14 National Center for Tumor Diseases, University of Heidelberg, Germany
* Correspondence to: Dr F. Lordick, National Center for Tumor Diseases, University of Heidelberg, Im Neuenheimer Feld 350, D-69120 Heidelberg, Germany. Tel: +49-6221-56-4801; Fax: +49-6221-56-8815; E-mail: florian.lordick{at}med.uni-heidelberg.de
Background: This study assessed the activity of the mAb cetuximab in combination with cisplatin and 5-fluorouracil (5-FU) in advanced esophageal squamous cell carcinoma.
Patients and methods: For a maximum of six 29-day cycles, patients received cisplatin 100 mg/m2, day 1, plus 5-FU 1000 mg/m2, days 1–5 (CF), either alone or in combination with cetuximab (CET–CF; 400 mg/m2 initial dose followed by 250 mg/m2 weekly thereafter). The primary end point was tumor response. Tumor material was obtained for analysis of KRAS mutation status.
Results: Sixty-two eligible patients were included, 32 receiving CET–CF and 30 CF. Cetuximab did not exacerbate grade 3/4 toxicity, except for rash (6% versus 0%) and diarrhea (16% versus 0%). The overall response rate according to RECIST criteria was 19% and 13% and the disease control rate 75% and 57% for the CET–CF and CF arms, respectively. With a median follow-up of 21.5 months, the median progression-free survival was 5.9 and 3.6 months and median overall survival 9.5 and 5.5 months for CET–CF and CF, respectively. No KRAS codon 12/13 tumor mutations were identified in 37 evaluated samples.
Conclusion: Cetuximab can be safely combined with CF chemotherapy and may increase the efficacy of standard CF chemotherapy.
Key words: cetuximab, chemotherapy, esophageal cancer, KRAS mutation, squamous cell carcinoma
Received for publication November 18, 2008. Revision received February 20, 2009. Accepted for publication February 23, 2009.