Abstract
Irinotecan or CPT-11, a new inhibitor of the nuclear enzyme topoisomerase 1, is active in metastatic colorectal cancer (CRC). CPT-11 appeared to be superior to supportive care and continuous infusion of 5-FU in patients with metastatic CRC after failure to 5-FU (1-3). SN-38 is believed to be the active metabolite of CPT-11 and is produced by the enzyme carboxylesterase (4-7). Hepatic metabolism by glicuronidation and subsequent biliary excretion is the most important route of elimination of SN-38 (8-10).
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References
Creemers G.J., Lund B. Verweij J.,1994, Topoisomerase I inhibitors. Topotecan and irinotecan. Cancer Treat Rev. 20: 73–96
Pinot H. C., 1997, Phase II trial of irinotecan in patients with metastatic colorectal carcinoma. J Clin Oncol 15: 2910–2919
Cunningham D., 1998, Randomized trial of irinotecan plus supportive care versus supportive care alone after fluorouracil failure in patients with metastatic colorectal cancer.Lancet, 352: 1413–1418
Iyer L., Raitan M.J.,1998, Clinical pharmacology of camptothecins. Cancer Chemother Pharmacol 42: 531–543
Chabot G.G., 1995, Population pharmacokinetics and pharmacodynamics of irinotecan (CPT-11) and active metabolite SN-38 during phase I trials. Ann Oncol 6: 141–151
Rivory L. P., Robert J.,1995, Identification and kinetics of a ß-glucuronide of SN-38 in human plasma after administration of the camptothecin derivative irinotecan (CPT-11). Cancer Chemother Pharmacol 36: 176–179
Gupta E., 1994, Metabolic fate of irinotecan in humans: correlation of glucuronidation with diarrhea. Cancer Res 54: 3723–3725
Van Groeningen C. J., 2000, Altered Pharmacokinetics and metabolism of CPT-11 in liver dysfunction: a need for guidelines. Clin Cancer Res 6: 1342–1346
Farabos C., 2000, Hepatic extraction, metabolism and biliary excretion of irinotecan in the isolated perfused rat liver. Proceedings of ASCO200 a, Abs 779
Kerr J. Z.,2000, A phase I study of irinotecan in pediatric patients: a pediatric oncology group study. Proceedings of ASCO, 200 a Abs 780
Fiorentini G., 2000, Global approach to hepatic metastases from colorectal cancer: indication and outcome of intra-arterial chemotherapy and other hepatic directed treatments. Med Oncol 17 163–173
Guichard S., 2000, CPT-11 converting carboxylesterase in tumor and normal colon and liver tissues. Proceeding of AACR 40: 340, Abs 2250
Van Groeningen C.J., 1997, Phase I clinical and pharmacokinetics study of 5 day CPT- 11 hepatic arterial infusion (HAI) chemotherapy. Proceedings of ASCO 16: 219a, Abs 768
Van der Vijgh W.J.F., 1998, Pharmacokinetics and pharmacodinamics of CPT-11 during 5 day hepatic arterial and intravenous infusion. Proceedings of AACR 39: 600, Abs 4082
Eisenhauer E., 2000 Phase I Clinical Trial Design in Cancer Drug Development. J Clin Oncol 18 3: 684–692
Longo GSA, 1998, Pretreatment of colon carcinoma cells with tomudex enhances 5-fluorouracil cytotoxicity. Clin Cancer Res 4: 469–473
Mans D.R., 1999, Sequence-dependent growth inhibition and DNA damage formation by the irinotecan 5-fluorouracil combination in human colon carcinoma cell lines. Eur J Cancer, 35: 1851–1861
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Fiorentini, G., Lucchi, S.R., Giovanis, P., Cantore, M., Guadagni, S., Papiani, G. (2002). Phase I Clinical Study of Irinotecan (CPT-11) Hepatic Arterial Infusion Chemotherapy in Hepatic Metastases from Colorectal Cancer: Preliminary Results. In: Habib, N.A. (eds) Multi-Treatment Modalities of Liver Tumours. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-0547-1_18
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DOI: https://doi.org/10.1007/978-1-4615-0547-1_18
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