Heterogeneity among lists of cautioned or prohibited drugs in protocols of early-phase oncology trials

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.