Pharmacokinetics of Irinotecan With and Without Panitumumab Coadministration in Patients With Metastatic Colorectal Cancer

Abstract

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.

Clinical Pharmacokinetics and Pharmacodynamics of the Epidermal Growth Factor Receptor Inhibitor Panitumumab in the Treatment of Colorectal Cancer

“…Nineteen patients received irinotecan (180 mg/m 2 intravenously) and panitumumab (6 mg/kg intravenously) [19]. In cycle 1, panitumumab was administered 3 days after irinotecan administration, while in cycle 2, panitumumab administration was directly followed by the administration of irinotecan.…”

The effective combination therapies with irinotecan for colorectal cancer

“…The pharmacokinetic profile of irinotecan co-administered with or without panitumumab is almost identical. Panitumumab does not effect on the pharmacokinetics of irinotecan or there are synergistic effects ( Yang et al, 2013 ).…”

Panitumumab: A Review of Clinical Pharmacokinetic and Pharmacology Properties After Over a Decade of Experience in Patients with Solid Tumors

“…Panitumumab is approved for use in combination regimens [1,2], and potential interactions with chemotherapy agents have been studied. In patients with mCRC, panitumumab had no effect on the pharmacokinetics of irinotecan [25,26]. In a phase 2 study of patients with non-small cell lung cancer (NSCLC), panitumumab was administered in combination with paclitaxel and carboplatin [27].…”