Multicenter phase II study of cetuximab and irinotecan as third line chemotherapy in patients (pts) with metastatic colorectal cancer (MCRC) previously treated with both irinotecan and oxaliplatin regimens

Abstract

13551 Background: Pts with chemotherapy-resistant MCRC have a really poor prognosis with few therapeutic options. Cetuximab (Erbitux®) is an IgG1 monoclonal antibody targeting the EGFR, shown to be effective in pts with EGFR-expressing MCRC refractory to prior irinotecan-based chemotherapy (Cunningham NEJM 2004). Methods: The goal of this multicenter phase II study is to investigate the safety and efficacy of cetuximab in combination with irinotecan as third line treatment in 40 pts with heavily pre-treated MCRC. From Jan to Dec 2005, 40 pts with EGFR-expressing MCRC, refractory to irinotecan, pre-treated with both irinotecan and oxaliplatin with fluorouracil or capecitabine combinations, and PS 0–2, were included to receive cetuximab (400 mg/m2 week 1 and 250 mg/m2 weekly thereafter) plus irinotecan (180 mg/m2 every 2 weeks) until tumour progression or unacceptable toxicity. Pts were analysed weekly for toxicity and every 12 weeks for response. Recruitment is completed. Currently, 38 pts are evaluable for toxicity (2 pts recently recruited) and 23 pts for response (16 pts on treatment for <12 weeks and 1 pt withdrew at week 6 due to lung thromboembolism not related to study treatment). Results: M/F 24/14, median age 63 years (range: 33–78), colon/rectum 23/15, ECOG PS=0/1/2 9/23/6, Metastatic sites 1/2/>2 16/19/3 (Liver 43%, lung 23%, nodes 17%, pelvic 5%, others 12%). A total of 418 weekly infusions were administered (mean: 11; range: 3–37). Preliminary efficacy data is as follows: 3 PR, 3 SD, 17 PD with an overall response rate of 13% (95% CI: 3–34%) and disease control rate of 26% (95% CI: 10–48%). Major toxicities (G 1–2/G 3–4) were: Acne-like skin rash 58/11%, Anemia 32/3%, Neutropenia 16/13%, Nausea-vomiting 32/0%, Diarrhoea 32/11%. Median time to progression was 3.5 months (Range: 1–10+) and median overall survival was 7.3 months (Range: 1.5–12+). Conclusions: These preliminary results suggest that cetuximab and irinotecan combination, is a reasonably effective treatment for pts with highly pre-treated MCRC with an acceptable toxicity profile No significant financial relationships to disclose.