This study examined the effects of panitumumab, a human monoclonal antibody against epidermal growth factor receptor (EGFR), on irinotecan pharmacokinetics. This phase I, open-label, multicenter, single-arm study enrolled patients with metastatic colorectal cancer (mCRC) without prior exposure to an EGFR inhibitor. In cycle 1, patients received irinotecan (180 mg/m(2) intravenously [IV]) on day 1 and panitumumab (6 mg/kg IV) on Day 4. In cycle 2 (2 weeks after cycle 1 panitumumab administration) and subsequent every-2-week cycles, patients received panitumumab followed immediately by irinotecan until disease progression or intolerability. Primary and secondary endpoints included Cmax and AUC of irinotecan after irinotecan infusion in cycles 1 and 2, and adverse events, respectively. Nineteen of 27 treated patients were eligible for pharmacokinetic analysis. Pharmacokinetic profiles of irinotecan with or without panitumumab coadministration were nearly identical. The 90% confidence intervals for ratios of geometric means for irinotecan Cmax and AUC with or without panitumumab were within the 80-125% interval, indicating that panitumumab had no apparent effects on irinotecan pharmacokinetics. Adverse events were as expected for irinotecan plus panitumumab combination therapy.
Keywords: SN-38; irinotecan; panitumumab; pharmacokinetics; safety.
© The Author(s) 2013.