(HealthDay News) – For patients with irinotecan-refractory metastatic colorectal cancer (CRC), dose escalation of cetuximab is well tolerated and may improve response and disease control rates, but patients experience more grade ≥2 skin reactions, according to a study published online July 2 in the Journal of Clinical Oncology.

Eric Van Cutsem, MD, PhD, of University Hospital Gasthuisberg in Leuven, Belgium, and colleagues investigated the effect of cetuximab dose escalation in 157 intent-to-treat patients with irinotecan-refractory metastatic CRC. Following 21 days of standard-dose (400mg/m² initial dose, then 250mg/m² per week) treatment, participants who developed no or mild skin reactions (grade ≤1) at the standard dose were randomly allocated to standard-dose (45 patients) or dose-escalated (44 patients; up to 500mg/m² per week) cetuximab. Patients with skin reactions grade ≥2 continued with standard-dose cetuximab and irinotecan.

The researchers found that the pharmacokinetic profiles were predictable across the dose range assessed. Cetuximab up to 500mg/m² per week was well tolerated, with comparable grade 3 and 4 adverse events between the groups. There was an increase in grade ≥2 skin reactions for the dose-escalation vs the standard-dosing group (59 vs 38%). Although some evidence for improved response rate (30 vs 16%) and disease control rate (70 vs 58%) was noted with dose escalation, no overall survival benefit was found. Patients with KRAS wild-type, compared with KRAS mutant tumors, had increased response rate with dose escalation vs standard dosing.

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“Cetuximab serum concentrations increased predictably with dose. Higher dose levels were well tolerated,” the authors write. “The possible indication for improved efficacy in the dose-escalation group warrants further investigation.”

Several authors disclosed financial ties to pharmaceutical companies, including Merck KGaA, which funded the study.

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