Docetaxel enhances the cytotoxicity of tetrahydropyranyladriamycin in a sequence-dependent manner.
BACKGROUND
Taxanes and anthracyclines are active against breast cancer. In this study we investigated the combined antitumor activity of these drugs, with particular regard to sequence-dependency.


METHODS
The combined antitumor activity of docetaxel and tetrahydropyranyladriamycin (THP) against two human breast cancer xenografts was assessed using an in vitro histoculture drug-response assay. The sequence-dependency of the combined cytotoxicity was evaluated by isobologram.


RESULTS
A synergistic antitumor activity of combined docetaxel + THP was exhibited against the R-27 xenograft when docetaxel was given first or simultaneously with THP. However, this synergism was diminished when THP was used before docetaxel. While an additive effect of combined docetaxel + THP was observed against MX-1 xenograft when docetaxel was given first or simultaneously with THP, this effect was not marked using the THP/docetaxel sequence.


CONCLUSIONS
Docetaxel increased the antitumor activity of THP, but only when administered before or simultaneously with THP.
Egawa
T
T
Department of Surgery, School of Medicine, Keio University, Tokyo, Japan.
Kubota
T
T
Furukawa
T
T
Otani
Y
Y
Watanabe
M
M
Furukawa
T
T
Kumai
K
K
Kitajima
M
M
D000328:Adult; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000188:drug therapy*; D000077143:Docetaxel; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004334:Drug Administration Schedule; D004357:Drug Synergism; D005260:Female; D006801:Humans; D020128:Inhibitory Concentration 50; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy*; D051379:Mice; D008819:Mice, Nude; D017239:Paclitaxel / Q000008:administration & dosage / Q000031:analogs & derivatives*; D043823:Taxoids; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
D043823:Taxoids; D000077143:Docetaxel; D004317:Doxorubicin; C027260:pirarubicin; D017239:Paclitaxel