Biomaterial Database

Future directions for clinical research with CPT-11 (irinotecan). 1996

D von Hoff

Institute for Drug Development, Texas Research Park, San Antonio 78245, USA.

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 as well as increased antitumour activity, which should be explored in phase I and II studies.

UI	MeSH Term	Description	Entries
D012106	Research	Critical and exhaustive investigation or experimentation, having for its aim the discovery of new facts and their correct interpretation, the revision of accepted conclusions, theories, or laws in the light of newly discovered facts, or the practical application of such new or revised conclusions, theories, or laws. (Webster, 3d ed)	Research Priorities,Laboratory Research,Research Activities,Research and Development,Activities, Research,Activity, Research,Development and Research,Priorities, Research,Priority, Research,Research Activity,Research Priority,Research, Laboratory
D002166	Camptothecin	An alkaloid isolated from the stem wood of the Chinese tree, Camptotheca acuminata. This compound selectively inhibits the nuclear enzyme DNA TOPOISOMERASES, TYPE I. Several semisynthetic analogs of camptothecin have demonstrated antitumor activity.	Camptothecine
D005260	Female		Females
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000077146	Irinotecan	A semisynthetic camptothecin derivative that inhibits DNA TOPOISOMERASE I to prevent nucleic acid synthesis during S PHASE. It is used as an antineoplastic agent for the treatment of COLORECTAL NEOPLASMS and PANCREATIC NEOPLASMS.	7-Ethyl-10-hydroxycamptothecin,CPT 11,CPT-11,Camptosar,Camptothecin-11,Irinotecan Hydrochloride,Irrinotecan,NK012 Compound,SN 38,SN 38 11,SN-38,SN-38-11,7 Ethyl 10 hydroxycamptothecin,CPT11,Camptothecin 11,SN3811
D000972	Antineoplastic Agents, Phytogenic	Agents obtained from higher plants that have demonstrable cytostatic or antineoplastic activity.	Antineoplastics, Botanical,Antineoplastics, Phytogenic,Agents, Phytogenic Antineoplastic,Botanical Antineoplastics,Phytogenic Antineoplastic Agents,Phytogenic Antineoplastics
D017321	Clinical Trials, Phase I as Topic	Works about studies performed to evaluate the safety of diagnostic, therapeutic, or prophylactic drugs, devices, or techniques in healthy subjects and to determine the safe dosage range (if appropriate). These tests also are used to determine pharmacologic and pharmacokinetic properties (toxicity, metabolism, absorption, elimination, and preferred route of administration). They involve a small number of persons and usually last about 1 year. This concept includes phase I studies conducted both in the U.S. and in other countries.	Clinical Trials, Phase I,Drug Evaluation, FDA Phase I,Evaluation Studies, FDA Phase I,Human Microdosing Trial,Phase 1 Clinical Trial,Phase I Clinical Trial,Phase I Clinical Trials,Clinical Trials, Phase 1,Drug Evaluation, FDA Phase 1,Drug Evaluation, FDA Phase I as Topic,Evaluation Studies, FDA Phase 1,Human Microdosing Trials,Microdosing Trials, Human,Phase 1 Clinical Trials,Microdosing Trial, Human,Trial, Human Microdosing,Trials, Human Microdosing
D017322	Clinical Trials, Phase II as Topic	Works about studies that are usually controlled to assess the effectiveness and dosage (if appropriate) of diagnostic, therapeutic, or prophylactic drugs, devices, or techniques. These studies are performed on several hundred volunteers, including a limited number of patients with the target disease or disorder, and last about two years. This concept includes phase II studies conducted in both the U.S. and in other countries.	Drug Evaluation, FDA Phase 2 as Topic,Drug Evaluation, FDA Phase II as Topic,Evaluation Studies, FDA Phase 2 as Topic,Evaluation Studies, FDA Phase II as Topic
D059004	Topoisomerase I Inhibitors	Compounds that inhibit the activity of DNA TOPOISOMERASE I.	DNA Topoisomerase I Inhibitor,DNA Topoisomerase III Inhibitor,DNA Topoisomerase III Inhibitors,DNA Type 1 Topoisomerase Inhibitor,DNA Type III Topoisomerase Inhibitor,DNA Type III Topoisomerase Inhibitors,Topoisomerase 1 Inhibitor,Topoisomerase 1 Inhibitors,Topoisomerase 3 Inhibitor,Topoisomerase 3 Inhibitors,Topoisomerase I Inhibitor,Topoisomerase III Inhibitor,Topoisomerase III Inhibitors,DNA Topoisomerase I Inhibitors,DNA Type 1 Topoisomerase Inhibitors,1 Inhibitor, Topoisomerase,3 Inhibitor, Topoisomerase,3 Inhibitors, Topoisomerase,I Inhibitor, Topoisomerase,III Inhibitor, Topoisomerase,III Inhibitors, Topoisomerase,Inhibitor, Topoisomerase 1,Inhibitor, Topoisomerase 3,Inhibitor, Topoisomerase I,Inhibitor, Topoisomerase III,Inhibitors, Topoisomerase 1,Inhibitors, Topoisomerase 3,Inhibitors, Topoisomerase I,Inhibitors, Topoisomerase III