title: New paradigm in dose-finding trials: patient-specific dosing and beyond phase I.
abstract: We propose a new paradigm for the clinical evaluation of new cancer therapies. It entails adjusting the search for the optimal dose on the basis of measurable patient characteristics that may be predictive of adverse responses to treatment, and extending this search beyond phase I and into phases II and III. We provide examples of (a) how the fine-tuning of dose may involve utilization of patient-specific attributes to obtain a personalized treatment regimen, and (b) how novel methods for phase I design can be used to update the working dose for the conduct of phase II and III cancer clinical trials. These examples should be interpreted as an enticement for the development of new methods to implement the proposed new paradigm.
authors.affiliation: Winship Cancer Institute, Atlanta, Georgia 30322, USA. Andre_rogatko@emory.org
authors.forename: André
authors.initials: A
authors.lastname: Rogatko
authors.forename: James S
authors.initials: JS
authors.lastname: Babb
authors.forename: Mourad
authors.initials: M
authors.lastname: Tighiouart
authors.forename: Fadlo R
authors.initials: FR
authors.lastname: Khuri
authors.forename: Gary
authors.initials: G
authors.lastname: Hudes
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage*; 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; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004341:Drug Evaluation; D015507:Drugs, Investigational / Q000008:administration & dosage; D006801:Humans; D020714:Maximum Tolerated Dose; D009369:Neoplasms / Q000188:drug therapy*; D011336:Probability; D012107:Research Design; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D015507:Drugs, Investigational