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

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/m(2) 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-second-week 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.

RCT Entities:   Population Interventions Outcomes