In vitro toxicity of taxol based anticancer drug combinations on human hemopoietic progenitors

The sequence dependency of the interaction of taxol with other anticancer d rugs is of clinical importance, and may be due to pharmacokinetic changes a nd/or to inherent differences in the sensitivity of target normal or cancer cells. This study presents results on the in vitro interaction of taxol wi th doxorubicin, cisplatin, etoposide and vinorelbine in alternate sequences on human hemopoietic progenitors (CFU-GM). Peripheral blood mononuclear no n adherent cells were exposed to IC50 of Taxol for 24 hours and then, for I hour to IC50 of each of the other drugs. In a second set of experiments th e reverse sequence was applied. The cell suspension was subsequently cultur ed to assay the growth of CFU-GM. A strong sequence dependency characterize s the combination taxol-vinorelbine, while for the other combinations the o rder of sequence appears to have little impact on in vitro toxicity on CFU- GM. Comparing results on CFU-GM with that obtained in vitro with the same c ombination sequences on cancer cell lines some remarkable differences show up. Studies on a normal human myeloid line may therefore have a place in pr eclinical evaluation of sequence of anticancer drug combinations.