title: Heterogeneity among lists of cautioned or prohibited drugs in protocols of early-phase oncology trials.
abstract: BACKGROUND
  To prevent potential drug-drug interaction, lists of cautioned or prohibited (C/P) drugs are commonly included in protocols of phases I and II cancer trials. Heterogeneity among lists may affect patient eligibility and comparability of results.
  
  
  METHODS
  Protocols of phase I/II trials conducted at an academic cancer centre between 2004 and 2009 were reviewed. All C/P drugs were collected and compared among trials.
  
  
  RESULTS
  Of 100 protocols reviewed, 77 protocols include lists of C/P drugs to prevent CYP3A4-, 2C9- and 2C19-related interactions and/or QT interval prolongation. Sixty-five protocols evaluating 38 unique study drugs include lists of CYP3A4-related C/P drugs. These lists contain 0-137 inhibitors [coefficient of variation (CV): 123%], 0-20 inducers (CV: 57%) and 10-157 substrates (CV: 76%). There is a high degree of inconsistency among protocols of the same study drug or from the same originator. Heterogeneity is also common for lists of C/P CYP2C9 and 2C19 drugs and for QT interval prolongation drugs. Approximately 20% protocols contain potential sources of confusion in their drug lists.
  
  
  CONCLUSIONS
  There is high degree of heterogeneity among lists of drugs C/P in protocols of oncology phase I/II trials. There is an urgent need to standardize these lists.
authors: Department of Medical Oncology and Hematology, Princess Margaret Hospital, University Health Network, Toronto, Canada.
authors: B
authors: B
authors: You
authors: G
authors: G
authors: Pond
authors: L L
authors: LL
authors: Siu
authors: J
authors: J
authors: Nagai
authors: R
authors: R
authors: Cheiken
authors: E
authors: E
authors: Chen
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D002317:Cardiovascular Agents / Q000494:pharmacology; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004347:Drug Interactions; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D017410:Practice Guidelines as Topic
chemical_list: D000970:Antineoplastic Agents; D002317:Cardiovascular Agents; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System