TY - JOUR
T1 - Cetuximab administered once every second week to patients with metastatic colorectal cancer: A two-part pharmacokinetic/pharmacodynamic phase I dose-escalation study
AU - Tabernero, J.
AU - Ciardiello, F.
AU - Rivera, F.
AU - Rodriguez-Braun, E.
AU - Ramos, F. J.
AU - Martinelli, E.
AU - Vega-Villegas, M. E.
AU - Roselló, S.
AU - Liebscher, S.
AU - Kisker, O.
AU - Macarulla, T.
AU - Baselga, J.
AU - Cervantes, A.
PY - 2009/11/25
Y1 - 2009/11/25
N2 - 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.
AB - 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.
KW - Cetuximab
KW - EGFR
KW - Every second week
KW - Metastatic colorectal cancer
KW - Pharmacokinetics
U2 - 10.1093/annonc/mdp549
DO - 10.1093/annonc/mdp549
M3 - Article
VL - 21
SP - 1537
EP - 1545
IS - 7
ER -
