Annals of Oncology Advance Access originally published online on November 22, 2005
Annals of Oncology 2006 17(3):450-456; doi:10.1093/annonc/mdj084
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© 2005 European Society for Medical Oncology
Cetuximab and irinotecan/5-fluorouracil/folinic acid is a safe combination for the first-line treatment of patients with epidermal growth factor receptor expressing metastatic colorectal carcinoma
1 University Hospital, Dresden; 2 University Hospital, Ulm; 3 Hannover Medical School, Hannover; 4 Merck KGaA, Darmstadt; 5 Klinikum Oldenburg gGmbH, Oldenburg, Germany
* Correspondence to: Dr C.-H. Köhne, Klinikum Oldenburg gGmbH, Department of Oncology and Hematology, Dr. Eden-Strasse 10, 26133 Oldenburg, Germany. Tel: +49-441-403-2611; Fax: +49-441-403-2654; E-mail: onkologie{at}klinikum-oldenburg.de
Background: To investigate the safety/tolerability of the EGFR-antibody cetuximab when added to irinotecan/5-fluorouracil (5-FU)/folinic acid (FA) for first-line treatment in patients with metastatic colorectal cancer (mCRC).
Patients and methods: Twenty-one patients with untreated, metastatic, EGFR-expressing CRC received cetuximab 400 mg/m2 as an initial dose, and thereafter 250 mg/m2 weekly. In addition, patients received infusional 5-FU (24 h) in two dose levels (1500 mg/m2, low 5-FU group, n = 6 or 2000 mg/m2, high 5-FU group, n = 15), plus FA at 500 mg/m2 and irinotecan at 80 mg/m2, weekly x6 q50d.
Results: Twenty patients were assessable for tolerability after the first cycle. There were no dose limiting toxicities (DLTs) in the low 5-FU group and three DLTs (20%) in the high 5-FU group (two patients with diarrhea grade 3 and one patient with diarrhea grade 4). In the low 5-FU group all six patients received >80% of the planned dose. In the high 5-FU group, seven of 14 patients (50%) received 
80% of the planned chemotherapy dose during the first cycle due to dosage reductions whilst treatment delays occurred in 10/14 patients. During the whole study period, the common grade 3/4 adverse events were acne-like rash (38%) and diarrhea (29%). Chemotherapy did not affect the pharmacokinetics of cetuximab determined at weeks 1 and 4. Fourteen patients (67%, 95% CI 47% to 87%) had a confirmed response, and six (29%) had stable disease. Median time to progression was 9.9 months [lower 95% confidence limit (CL) 7.9, upper 95% CL not reached]. Median survival time was 33 months (lower CL 20, upper CL not reached). Four patients received secondary surgery with curative intent, and a fifth was potentially eligible for surgery but declined.
Conclusions: Addition of cetuximab to weekly infusional 5-FU/FA plus irinotecan is safe and first data suggest a promising activity. The 5-FU dose of 1500 mg/m2 is recommended for further studies.
Key words: cetuximab, irinotecan, chemotherapy, metastatic colorectal cancer
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