title: The evolution of phase I trials in cancer medicine: a critical review of the last decade.
abstract: The advent of targeted therapies, combined with an unsustainable rate of failure in oncology drug development, has resulted in a number of new approaches to clinical trials.  Early clinical trials are no exception, with efforts to improve the eventual success rate of late stage trials through evolving phase I trial methodologies, the addition of extensive pharmacodynamic studies, and early adoption of patient selection strategies.  Unfortunately, some of these new approaches have met with mixed results. Furthermore, no clear metrics are available to determine whether these designs are more successful than previous strategies. This review examines the evolution of phase I trials and draws upon several examples of strategies that have been successful as well as those that have not, and outlines a pragmatic approach to phase I trials as our understanding of the molecular biology of individual malignancies emerges.
authors: Breast Department of Clinical Research, South Texas Accelerated Research Therapeutics, San Antonio, TX 78229, USA. atolcher@start.stoh.com
authors: Anthony W
authors: AW
authors: Tolcher
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D017321:Clinical Trials, Phase I as Topic; D016503:Drug Delivery Systems / Q000379:methods*; D000077156:Gefitinib; D006801:Humans; D020714:Maximum Tolerated Dose; D058990:Molecular Targeted Therapy / Q000379:methods; D009369:Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy*; D010793:Phthalazines / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography; D047428:Protein Kinase Inhibitors / Q000493:pharmacokinetics; D011725:Pyridines / Q000493:pharmacokinetics; D011799:Quinazolines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D010793:Phthalazines; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D011799:Quinazolines; C404768:vatalanib; D000077156:Gefitinib