Cetuximab administered once every second week to patients with metastatic colorectal cancer: A two-part pharmacokinetic/pharmacodynamic phase I dose-escalation study

J. Tabernero, F. Ciardiello, F. Rivera, E. Rodriguez-Braun, F. J. Ramos, E. Martinelli, M. E. Vega-Villegas, S. Roselló, S. Liebscher, O. Kisker, T. Macarulla, J. Baselga, A. Cervantes

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Abstract

Background: This phase I dose-escalation study was designed to determine the maximum tolerated dose (MTD) and recommended dose of cetuximab administered on an every-second-week schedule to patients with metastatic colorectal cancer, on the basis of safety, pharmacokinetic and pharmacodynamic evaluation. Patients and methods: The study comprised two parts: a 6-week cetuximab monotherapy dose-escalation phase and a subsequent combination therapy phase, during which patients received cetuximab, at the same dose/schedule as in the monotherapy phase, followed by irinotecan plus infusional 5-fluorouracil/folinic acid (FOLFIRI). Patients in the control group received cetuximab as a 400 mg/m2 initial dose, then 250 mg/m 2/week and in the dose-escalation group, at 400-700 mg/m 2, every second week. Results: Sixty-two patients were included in the study. The MTD of cetuximab administered on an every-secondweek schedule was not reached. The safety profiles were similar across all groups. Response rates in the cetuximab monotherapy and combination therapy phases were 15% and 42%, respectively. Trough levels for the 500, 600 mg/m 2 and standard weekly regimens were comparable. Conclusion: Cetuximab can be safely administered once every second week at doses between 400 and 700 mg/m 2, with 500 mg/m 2 being the most convenient and feasible dose for future studies. © The Author 2009. Published by Oxford University Press.
Original languageEnglish
Pages (from-to)1537-1545
JournalAnnals of Oncology
Volume21
Issue number7
DOIs
Publication statusPublished - 25 Nov 2009

Keywords

  • Cetuximab
  • EGFR
  • Every second week
  • Metastatic colorectal cancer
  • Pharmacokinetics

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