Pharmacokinetics of irinotecan in combination with biweekly cetuximab in patients with advanced colorectal cancer.
BACKGROUND
The effect of biweekly cetuximab (CTX) on the pharmacokinetics of CPT-11 and its metabolites was evaluated in this prospective, paired, crossover study.


METHODS
Patients with epidermal growth factor receptor-positive advanced colorectal cancer received infusions of CPT-11 (180 mg/m(2); FOLFIRI schedule) every second week. CTX (500 mg/m(2) for 120 min) was infused on day 2, followed by biweekly infusions (500 mg/m(2) for 120 min). Plasma samples were analysed on day 1 of cycle 1 (CPT-11 monotherapy) and on day 1 of cycle 3 or 4 (CPT-11 plus CTX). The endpoint of this study was to evaluate differences in plasma concentrations of CPT-11 and metabolites between cycle 1 and cycle 3 (or 4).


RESULTS
Generally, there was little difference in CPT-11 pharmacokinetics when combined with CTX in the 11 enrolled patients. However, a significantly lower area under the concentration-time curve from 0-48 hours was observed for the SN-38 glucuronide metabolite with combination therapy versus monotherapy (by 27%, p<0.05).


CONCLUSIONS
CTX has no clinically relevant impact on the pharmacokinetics of CPT-11 or its activation into SN-38; however, there may be a delay in detoxification of SN-38 by beta-D-glucuronidation.
Czejka
Martin
M
Department of Clinical Pharmacy and Diagnostics, University of Vienna, Althanstrasse 14, A-1090 Vienna, Austria. martin.czejka@univie.ac.at
Gruenberger
Birgit
B
Kiss
Andreas
A
Farkouh
Andre
A
Schueller
Johannes
J
D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D019540:Area Under Curve; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D018592:Cross-Over Studies; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000077146:Irinotecan; D000068818:Cetuximab; D002166:Camptothecin