A Phase II Study of High-Dose Cetuximab plus Irinotecan in Colorectal Cancer Patients with KRAS Wild-Type Tumors Who Progressed after Standard Dose of Cetuximab plus Irinotecan

Objectives: We conducted a phase II clinical trial of high-dose cetuximab plus irinotecan in KRAS wild-type patients who progressed on standard-dose cetuximab plus irinotecan. Methods: Patients who progressed within 4 weeks from receiving a minimum of 6 weeks of standard-dose cetuximab plus irinotecan were included in this study. Cetuximab was administered at 500 mg/m2/week and irinotecan was administered at the same dose/schedule on which each individual patient had previously progressed. The study was closed early after having met its primary end point. Results: Twenty patients were treated. The regimen was found to be efficacious, with 9 patients achieving disease control lasting more than 12 weeks. The median progression-free survival and overall survival were 2.8 and 6.6 months, respectively. The toxicity profile was favorable, with the exception of grade 3–4 hypomagnesemia which was noted in 25% of patients. Conclusions: High-dose cetuximab plus irinotecan rechallenge can re-elicit clinical benefits in patients who have previously failed cetuximab plus irinotecan treatment. The clinical benefits are modest and may be related to cetuximab rechallenge rather than cetuximab dose escalation.