Etoposide and doxorubicin antagonize the in vitro activity of paclitaxel in human non-small cell lung cancer cell lines.
OBJECTIVE
To explore in vitro interactions of paclitaxel with other agents also active against non-small cell lung cancer in the hope of identifying promising combinations for clinical evaluation.


METHODS
We measured the cytotoxic effects of paclitaxel when used alone or in combination with vinblastine, cisplatin, etoposide or doxorubicin in final concentrations covering 3-4 Logs in up to five cell lines using a 96-well plate MTT assay. Drug interactions were analyzed with the isobologram method of Steel and Peckham and bidimensional plots.


RESULTS
We detected no interactions between paclitaxel and cisplatin in two cell lines. Despite sharing a molecular site of action, there were no interactions between paclitaxel and vinblastine in two cell lines. In contrast, significant antagonism was detected between paclitaxel and etoposide or doxorubicin in 4/5 cell lines tested.


CONCLUSIONS
We failed to identify potentially synergistic paclitaxel-based combinations for the treatment of non-small cell lung cancer. Whether the observed in vitro antagonism between paclitaxel and etoposide or doxorubicin predicts for similar interaction in the clinical use of these drugs in combination is unknown.
Viallet
J
J
Department of Medicine, Hôpital Notre-Dame, Montreal, P.Q., Canada.
Tsao
M S
MS
Gallant
G
G
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D002945:Cisplatin / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000494:pharmacology*; D004334:Drug Administration Schedule; D004347:Drug Interactions; D004354:Drug Screening Assays, Antitumor; D005047:Etoposide / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000008:administration & dosage / Q000037:antagonists & inhibitors*; D014407:Tumor Cells, Cultured; D014747:Vinblastine / Q000008:administration & dosage
D014747:Vinblastine; D005047:Etoposide; D004317:Doxorubicin; D017239:Paclitaxel; D002945:Cisplatin