The suitability of selected new anticancer agents for infusional therapy and the effects of others on infusional therapy practices.
The comprehensive development of new antineoplastic agents mandates a thorough evaluation of schedule-dependent cytotoxicity and toxicity. This report focuses on the topoisomerase I inhibitors as an example of a novel class of anticancer agents in exposure duration may be a critical factor in the achievement of an optimal therapeutic index. The mechanistic and pharmacologic determinants and rationale for using protracted exposure schedules in administering several topoisomerase I inhibitors are discussed. The review also discusses dihydropyrimidine dehydrogenase as a pharmacologic target, enabling administration of oral fluoropyrimidines.
Rowinsky
E K
EK
Division of Pharmacology and Experimental Therapeutics, Johns Hopkins Oncology Centre, Baltimore, Maryland 21287-8934, USA.
D000284:Administration, Oral; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D042943:Dihydrouracil Dehydrogenase (NADP); D016503:Drug Delivery Systems; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007263:Infusions, Parenteral; D009369:Neoplasms / Q000188:drug therapy*; D010088:Oxidoreductases / Q000037:antagonists & inhibitors; D059004:Topoisomerase I Inhibitors; D014498:Uracil / Q000008:administration & dosage / Q000031:analogs & derivatives
D000972:Antineoplastic Agents, Phytogenic; D004791:Enzyme Inhibitors; D059004:Topoisomerase I Inhibitors; C073482:eniluracil; D014498:Uracil; D010088:Oxidoreductases; D042943:Dihydrouracil Dehydrogenase (NADP); D005472:Fluorouracil; D002166:Camptothecin