title: Drug development in oncology: classical cytotoxics and molecularly targeted agents.
abstract: There is an apparent need to improve the speed and efficiency of oncological drug development. Furthermore, strategies traditionally applied to the development of standard cytotoxic chemotherapy may not be appropriate for molecularly targeted agents. This is particularly the case for exploratory Phase 1 and 2 trials. Conventional approaches to determine dose based on maximum tolerability and efficacy based on objective tumour response may not be suitable for targeted agents, since many of them have a wide therapeutic index and inhibit tumour growth without demonstrable cytotoxicity. Instead, exploratory trials of targeted agents may have to focus on other end-points such as pharmacological effects and disease stabilization. Thus, there is an increasing interest in making the best possible use of biomarkers and pharmacogenomics in early phases of drug development.
authors.affiliation: Medical Oncology Branch, Center for Cancer Research and Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD 20892, USA.
authors.forename: Shivaani
authors.initials: S
authors.lastname: Kummar
authors.forename: Martin
authors.initials: M
authors.lastname: Gutierrez
authors.forename: James H
authors.initials: JH
authors.lastname: Doroshow
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Murgo
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017321:Clinical Trials, Phase I as Topic; D016503:Drug Delivery Systems; D015195:Drug Design; D004347:Drug Interactions; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D010597:Pharmacogenetics; D013678:Technology, Pharmaceutical
chemical_list: D000970:Antineoplastic Agents