AI Article Synopsis
- The study explored if the combination of irinotecan and cetuximab could affect the pharmacokinetics of irinotecan and its metabolites in patients with advanced colorectal cancer.
- Patients received a standard irinotecan regimen alongside cetuximab, with plasma samples tested after initial infusions.
- Results showed no significant changes in drug levels or how the body processed irinotecan when used with cetuximab, indicating that cetuximab does not have a meaningful effect on irinotecan's effectiveness or breakdown.
Article Abstract
Background: The present study was designed to investigate whether a combination of irinotecan and the monoclonal antibody cetuximab shows potential to modulate the pharmacokinetics of irinotecan and its metabolites.
Patients And Methods: All patients, suffering from advanced colorectal cancer, received irinotecan (350 mg/m2) every third week and cetuximab as a loading dose (400 mg/m2) on day 2, followed by a weekly maintenance dose (250 mg/m2). Plasma samples were analysed after the first (MONO) and second (CMAB) irinotecan infusions.
Results: No significant alterations in the plasma concentrations and pharmacokinetics of irinotecan and its metabolites were observed after combination with cetuximab. Only differentiation of irinotecan into lactone and carboxylate plasma concentrations resulted in a distinctly lower cmax of the active lactone in the CMAB and a significantly higherAUClast in the MONO schedule (p<0.02).
Conclusion: The results of this study indicated that cetuximab has no clinically relevant impact on the pharmacokinetics of irinotecan, its activation into SN-38, or its detoxification by beta-D-glucuronidation.
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