Cetuximab in combination with irinotecan/5-fluorouracil (5-FU)/folinic acid (FA) (FOLFIRI) in second and third-line treatment of metastatic colorectal cancer (mCRC): Safety and efficacy analysis

Abstract

3558 Background: The Folfiri regimen demonstrated high efficacy and favorable safety profile compared to irinotecan plus bolus 5-FU/FA (IFL regimen) or irinotecan alone. Folfiri is a standard option in first line treatment of mCRC. Cetuximab, an IgG1 monoclonal antibody targeting the epidermal growth factor receptor (EGFR), which is commonly expressed in mCRC, is approved in France in combination with irinotecan after failure of an irinotecan-based therapy. We have prospectively evaluated the combination cetuximab-FOLFIRI in patients with mCRC refractory to FOLFIRI administered in first line treatment. Methods: Patients with EGFR-expressing mCRC, who progressed following first line treatment with FOLFIRI regimen were eligible for this study. Treatment consisted of cetuximab (initial dose 400 mg/m2 followed by 250mg/m2/week) combined with FOLFIRI (given every 2 weeks: irinotecan 180 mg/m2, FA 400 mg/m2 and 5-FU 400 mg/m2 bolus plus 2400 mg/m2/46-h infusion) until either disease progression or unacceptable toxicity. Tumor reponse was assessed by CT scan every 2 months (OMS criteria), and adverses events were registered. Results: 41 patients where included from 09/2004 to 11/2005. 78% Male/ 22% Female, mean age 63 years, median KPS 80, 68% colon primary tumour. 5 patients were treated in second line, 24 patients in third line and 12 in fourth line or more. 40 patients are evaluable for response. They were 8 objective responses (20%) and 11 patients with stable disease (27.5%). The median progression free survival was 4,3 months and the median overall survival was 5 months. 61 % of the 41 patients experienced grade 3–4 adverses events, the most frequent of which were leucopenia (16%), asthenia (9%), vomiting and diarrhoea (5%), and acneiform skin rash in 11 patients (24%), severe xerosis (7%). 6/11 patients who experienced acneiform eruption grade 3 were alive at 12 months. Conclusions: The combination of cetuximab with FOLFIRI demonstrated promising efficacy and acceptable safety profile without increasing chemotherapy adverse reactions. A prospective randomised trial would confirm the advantage of FOLFIRI over irinotecan alone in combination with cetuximab. No significant financial relationships to disclose.