title: Lessons Learned: Dose Selection of Small Molecule-Targeted Oncology Drugs.
abstract: Evaluation of dose plays a critical role in a successful oncology development program. Typically for oncology agents, the first-in-man phase I dose-escalation trials are conducted to determine a maximum tolerated dose (MTD). This MTD is taken forward into subsequent trials to establish the safety and efficacy of the drug product. Although this approach was appropriate historically for cytotoxics, the application of MTD as the recommend phase II dose has been problematic for the newer small molecule-targeted oncology agents. Promising alternative approaches using dose and exposure exploration, including lessons learned from recent targeted oncology agent development and approvals, are summarized and discussed. Clin Cancer Res; 22(11); 2630-8. ©2016 AACR SEE ALL ARTICLES IN THIS CCR FOCUS SECTION, "NEW APPROACHES FOR OPTIMIZING DOSING OF ANTICANCER AGENTS".
authors.affiliation: d3 Medicine LLC, Parsippany, New Jersey.
authors.forename: Julie M
authors.initials: JM
authors.lastname: Bullock
authors.affiliation: Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Atiqur
authors.initials: A
authors.lastname: Rahman
authors.affiliation: Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland. qi.liu@fda.hhs.gov.
authors.forename: Qi
authors.initials: Q
authors.lastname: Liu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D004305:Dose-Response Relationship, Drug; D006801:Humans; D020714:Maximum Tolerated Dose; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors