title: Clinical trial designs for targeted agents.
abstract: With an increasing number of targeted agents available for testing, clinical trials must be rationally designed based on sound knowledge of the molecular mechanisms linking target and disease, fortified by strong preclinical data demonstrating how this relationship is modified by the targeted agent. Patients and resources are precious and should be expended judiciously on clinical trials that are well planned. Although traditional trial designs and endpoints may not be adequate for developing contemporary targeted drugs, transiting directly from phase I to phase III testing should be avoided except in distinct circumstances. Increased research efforts should be spent on the prospective evaluation and validation of novel biologic endpoints and innovative clinical designs, such that promising targeted agents can be effectively developed to benefit the care of cancer patients.
authors.affiliation: Department of Medical Oncology, Princess Margaret Hospital, University Health Network, 610 University Avenue, Toronto, ON M5G 2M9, Canada.
authors.forename: Brigette B Y
authors.initials: BB
authors.lastname: Ma
authors.forename: Carolyn D
authors.initials: CD
authors.lastname: Britten
authors.forename: Lillian L
authors.initials: LL
authors.lastname: Siu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D001549:Benzamides; D015415:Biomarkers; D001713:Biphenyl Compounds; D002986:Clinical Trials as Topic / Q000379:methods*; D017321:Clinical Trials, Phase I as Topic / Q000379:methods; D017322:Clinical Trials, Phase II as Topic / Q000379:methods; D017326:Clinical Trials, Phase III as Topic / Q000379:methods; D018849:Controlled Clinical Trials as Topic / Q000379:methods; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D000068877:Imatinib Mesylate; D061965:Matrix Metalloproteinase Inhibitors; D051379:Mice; D009363:Neoplasm Proteins / Q000032:analysis / Q000037:antagonists & inhibitors; D009369:Neoplasms / Q000188:drug therapy*; D009930:Organic Chemicals; D017063:Outcome Assessment, Health Care; D018579:Patient Selection; D010654:Phenylbutyrates; D010879:Piperazines / Q000627:therapeutic use; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011743:Pyrimidines / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic / Q000379:methods; D051381:Rats
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D015415:Biomarkers; D001713:Biphenyl Compounds; D004791:Enzyme Inhibitors; D061965:Matrix Metalloproteinase Inhibitors; D009363:Neoplasm Proteins; D009930:Organic Chemicals; D010654:Phenylbutyrates; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; C113281:Bay 12-9566; D011505:Protein-Tyrosine Kinases