Irinotecan-cisplatin interactions assessed in cell-based screening assays: cytotoxicity, drug accumulation and DNA adduct formation in an NSCLC cell line

Purpose The use of in vitro drug cytotoxicity assays for the assessment of drug–drug interactions that lead to synergy may not take into account the many cellular determinants responsible for combination effects. Administration of the anticancer drug CPT-11, for example, is associated with rapid conversion of drug from its active lactone form to the inactive carboxylate form. Thus it is difficult to model, in vitro, the behavior of this drug when used as a single agent and when used in a combination setting, this factor may contribute to the interactions measured. Therefore, the objective of this study was to examine the influence of CPT-11 lactone ratio on the cellular accumulation of CPT-11 when used as a single agent and under conditions where it is used in combination with cisplatin.