Research & Innovation
Publications
Metabolic activation of irinotecan during intra-arterial chemotherapy of metastatic colorectal cancer
PMU Author
R. Terkola
All Authors
M. Czejka, A. Kiss, C. Koessner, R. Terkola, D. Ettlinger, J. Schueller
Journal association
ANTICANCER RESEARCH
Abstract
Biotransformation of irinotecan (CPT-11) into its pharmacologic active metabolite SN-38 was investigated in patients treated for advanced colorectal cancer. A dose of 180 mg/m(2) CPT-11 was administered to 6 patients by 60 min hepatic intra-arterial infusion (HAI) via a surgically implanted Port-a-Cath® system. Blood samples were collected from 0 to 360 min after start of HAI, and CPT-11 plus metabolites were analysed by a selective reversed phase HPLC method. The objective of this study was to evaluate the extent to which SN-38 is generated after HAI of irinotecan given at a low dose of 180 mg/m(2). In a second investigation, CPT-11 was administered via conventional intravenous infusion (dose 180 mg/m(2), 60 min infusion time, 11 patients) and CPT-11 plus metabolites were quantified using identical analytical procedure. Compared to i.v. infusion, the pharmacokinetics of CPT-11 and SN-38 were altered by HAI. The mean c(max) of CPT-11 after HAI was reduced by 37%, whereas the mean c(max) of SN-38 increased by 60%. HAI resulted in a desired, increased metabolic conversion of CPT-11 into SN-38 and might improve the regional availability of the pharmacologic active metabolite SN-38 at the site of tumor. Plasma concentrations of the metabolites SN-38 glucuronide and APC remained unaffected by the route of administration.
Keywords
Humans, Aged, Middle Aged, Time Factors, Dose-Response Relationship, Drug, Neoplasm Metastasis, Colorectal Neoplasms/drug therapy, Biotransformation, Camptothecin/administration & dosage, Infusions, Intra-Arterial, Irinotecan