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

Abstract

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/m(2) is recommended for further studies.

Final analysis of colorectal cancer patients treated with irinotecan and 5-fluorouracil plus folinic acid neoadjuvant chemotherapy for unresectable liver metastases

“…Emerging data suggest that the addition of targeted biological agents to such regimens will further improve efficacy. Indeed, Folprecht et al (2006) reported a median survival time of 33 months, using cetuximab, an EGFRtargeted monoclonal antibody, in combination with irinotecan/5-FU/FA. In a randomised phase III trial, cetuximab was shown to increase response rate, progression-free survival and resection rate over FOLFIRI alone in patients with advanced CRC, with the PFS benefit being greatest for those patients with liver-only metastases (Van Cutsem et al, 2007).…”

Management of advanced colorectal cancer: state of the art

“…Cetuximab was subsequently investigated first-line in combination with irinotecan/infusional 5-FU/FA (Rougier et al, 2004;Folprecht et al, 2006). Initial results showed these combinations to be safe with promising activity.…”

Cetuximab, a chimeric human mouse anti-epidermal growth factor receptor monoclonal antibody, in the treatment of human colorectal cancer

“…Cetuximab has a mean volume of distribution of 45.2-61.9 ml/kg, approximately equivalent to plasma volume, at intravenous doses of 20-100 mg/m 2 given at weekly intervals for 4-12 weeks, as demonstrated in two phase I studies (Folprecht et al, 2005). The major route of cetuximab clearance is through binding of the antibody to EGFR in many tissues, including the liver and the skin, which subsequently internalizes the antibody-receptor complex and removes it from circulation (Baselga et al, 2000;Robert et al, 2001;Folprecht et al, 2005). Cetuximab clearance decreases with increasing dose, indicating saturation of the metabolic pathway and nonlinear pharmacokinetics at lower doses.…”

“…In patients with metastatic CRC treated with cetuximab 400 mg/m 2 as initial dose followed by 250 mg/m 2 weekly in association with irinotecan either alone or with FA and 5-FU, mean peak serum concentrations of 153-202 mg/ml and the area under the plasma concentration-time curve values of 21 520-17 337 mg/h/ml were recorded between weeks 1 and 4 of treatment (Debaldo et al, 2003;Folprecht et al, 2005). Cetuximab has a mean volume of distribution of 45.2-61.9 ml/kg, approximately equivalent to plasma volume, at intravenous doses of 20-100 mg/m 2 given at weekly intervals for 4-12 weeks, as demonstrated in two phase I studies (Folprecht et al, 2005).…”

“…It has a mean serum elimination half-life of 79-129 h at a dosage of 400 mg/m 2 followed by 250 mg/m 2 weekly, after 1-4 weeks of treatment. Moreover, several studies suggest that continuous saturation of the EGFR is achieved and maintained in the majority of patients with an initial dose of 400-500 mg/m 2 , followed by 200-300 mg/m 2 weekly (Debaldo et al, 2003;Folprecht et al, 2005).…”