title: [Dose escalation strategies of molecular target drugs].
abstract: During the last decade, advances in cell biology and molecular biology have produced molecular targets for cancer treatment, and many molecular targeted drugs, or "cytostatic agents," have been clinically evaluated. Dose limiting toxicities are not always observed with these drugs and there is little relationship between drug dose and biological effect. Therefore, the traditional strategy used in the clinical development of cytotoxic drugs may not be appropriate for evaluation of these cytostatic agents. In order to determine the optimum dose for these agents, new clinical strategies must be developed on the basis of the following considerations: 1. the relationship between the effective plasma concentration in preclinical data and mean trough plasma levels in clinical trials, 2. changes in plasma concentration in the tumor or expression of molecular targets according to dose escalation, and 3. application of surrogate markers for biological activity.
authors.affiliation: Division of GI Oncology/Digestive Endoscopy, National Cancer Center Hospital East, Kashiwa, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Tahara
authors.forename: Y
authors.initials: Y
authors.lastname: Sasaki
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000008:administration & dosage*; D006801:Humans; D006877:Hydroxamic Acids / Q000008:administration & dosage*; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors*; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; C100342:marimastat; D008666:Metalloendopeptidases