Future directions for clinical research with CPT-11 (irinotecan)

European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)
D von Hoff

Abstract

CPT-11 is a new agent with a unique mechanism of action, namely the inhibition of topoisomerase I. An examination of data from the laboratory reveals several leads which should be pursued in the clinic. A dose-response effect for CPT-11 activity has been noted in the human tumour cloning assay. CPT-11 has activity against breast and mesothelioma colony-forming units in a human tumour cloning assay, and has in vivo activity against a number of paediatric malignancies. Promising combinations in preclinical in vivo models include CPT-11/mitomycin C and CPT-11/cytosine arabinoside. There is incomplete cross-resistance among topoisomerase I inhibitors, suggesting that combinations of topoisomerase I inhibitors should be investigated. Several natural products have been identified which have potential to decrease CPT-11-induced diarrhoea. The level of carboxylesterase in a patient's tumour appears to be related to the in vitro activity of CPT-11, suggesting that measurement of carboxylesterase in a patient's tumour could be used to identify patients who are most likely to respond to treatment with CPT-11. These preclinical findings suggest substantial further clinical potential for CPT-11 in terms of decreased CPT-11-induced diarrhoea...Continue Reading

Citations

Oct 25, 2000·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·E JonssonR Larsson
Oct 20, 2005·Journal of Bioscience and Bioengineering·Tzung-Han ChouI-Ming Chu
Nov 1, 2005·Chemico-biological Interactions·Janice L HyattPhilip M Potter
Mar 18, 2011·American Journal of Health-system Pharmacy : AJHP : Official Journal of the American Society of Health-System Pharmacists·Christopher J CampenAmanda F Baker
Nov 9, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Gayle S JamesonDaniel D Von Hoff

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