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.


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.


CONCLUSIONS
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.
Tabernero
J
J
Medical Oncology Service, Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain. Electronic address: jtabernero@vhebron.net.
Ciardiello
F
F
Division of Medical Oncology, Department of Experimental and Clinical Medicine 'F. Magrassi and A. Lanzara', Second University of Naples, Naples, Italy.
Rivera
F
F
Department of Medical Oncology, Hospital Universitario Marqués de Valdecilla, Santander.
Rodriguez-Braun
E
E
Department of Hematology and Medical Oncology, Hospital Clinico Universitario, University of Valencia, Spain.
Ramos
F J
FJ
Medical Oncology Service, Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain.
Martinelli
E
E
Division of Medical Oncology, Department of Experimental and Clinical Medicine 'F. Magrassi and A. Lanzara', Second University of Naples, Naples, Italy.
Vega-Villegas
M E
ME
Department of Medical Oncology, Hospital Universitario Marqués de Valdecilla, Santander.
Roselló
S
S
Department of Hematology and Medical Oncology, Hospital Clinico Universitario, University of Valencia, Spain.
Liebscher
S
S
Global Biostatistics.
Kisker
O
O
Medical Sciences Oncology, Merck KGaA, Darmstadt, Germany.
Macarulla
T
T
Medical Oncology Service, Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain.
Baselga
J
J
Medical Oncology Service, Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain.
Cervantes
A
A
Department of Hematology and Medical Oncology, Hospital Clinico Universitario, University of Valencia, Spain.
D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary*; D004305:Dose-Response Relationship, Drug; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007124:Immunoenzyme Techniques; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D015996:Survival Rate; D014018:Tissue Distribution; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000077146:Irinotecan; C512478:EGFR protein, human; D066246:ErbB Receptors; D000068818:Cetuximab; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin