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Sequence-dependent cytotoxicity of etoposide and paclitaxel in human breast and lung cancer cell lines
1Division of Hematology/Oncology, Mayo Clinic Jacksonville, FL 32224, USA.
Purpose:
To evaluate the effect of schedule on the interaction of etoposide with paclitaxel in vitro against the A549 human lung cancer cell line and the MDA-231 and MCF-7 human breast cancer cell lines.
Methods:
Exposure schedules that were 24-h concurrent, 24-h sequential, and sequential 24-h with a 24-h intervening drug-free period were quantitatively evaluated by the use of the median-effect principle and the combination index. The clonogenic assay was used to assess cytotoxicity, and calculations were done with computer software.
Results:
Concurrent exposures were less than additive in two of the three cell lines tested. Sequential 24-hour and sequential 24-h with an intervening 24-h drug-free period showed synergism at high effect levels in all three cell lines. Similar synergistic interactions were found when either agent was administered first.
Conclusions:
These results show a schedule-dependent cytotoxic interaction between etoposide and paclitaxel in the human lung and breast cancer cell lines evaluated, with optimal synergism occurring with sequential, but not with concurrent, treatment.