Sequence-dependent cytotoxicity of etoposide and paclitaxel in human breast and lung cancer cell lines.
OBJECTIVE
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.
Perez
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EA
Division of Hematology/Oncology, Mayo Clinic Jacksonville, FL 32224, USA.
Buckwalter
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CA
D000972:Antineoplastic Agents, Phytogenic / Q000633:toxicity*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000633:toxicity*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004334:Drug Administration Schedule; D004347:Drug Interactions; D005047:Etoposide / Q000633:toxicity*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017239:Paclitaxel / Q000633:toxicity*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000972:Antineoplastic Agents, Phytogenic; D005047:Etoposide; D017239:Paclitaxel