Antitumor activity of paclitaxel against human breast carcinoma xenografts serially transplanted into nude mice.
BACKGROUND
Paclitaxel (BMS-181339: Taxol) is a promising agent against previously treated breast cancer. The antitumor activity of paclitaxel was evaluated using five human breast carcinoma xenografts in nude mice.


METHODS
Paclitaxel at 20 mg/kg dissolved in 0.2 ml ethanol/cremophor EL solution was administered intraperitoneally daily for 5 days.


RESULTS
Paclitaxel showed significant antitumor activity against MCF-7 and MX-1, but only limited activity against the other three xenografts (R-27, Br-10, and T-61), suggesting its substantially different antitumor spectrum from conventional antibreast cancer drugs. The different sensitivity of xenografts to paclitaxel was successfully reproduced in vitro using the MTT assay, when the cutoff concentration of paclitaxel was 20 microg/ml.


CONCLUSIONS
Since no significant differences were observed in the pharmacokinetics of paclitaxel in sensitive and resistant tumor cell lines, the efficacy of this agent seemed to depend on the sensitivity of tumor cells rather than the intratumoral concentration of agent.
Kubota
T
T
Department of Surgery, School of Medicine, Keio University, Tokyo, Japan.
Matsuzaki
S W
SW
Hoshiya
Y
Y
Watanabe
M
M
Kitajima
M
M
Asanuma
F
F
Yamada
Y
Y
Koh
J I
JI
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000493:pharmacokinetics / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004396:Coloring Agents; D003520:Cyclophosphamide / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D016685:Mitomycin / Q000494:pharmacology; D009368:Neoplasm Transplantation; D017239:Paclitaxel / Q000493:pharmacokinetics / Q000494:pharmacology*; D013778:Tetrazolium Salts; D013844:Thiazoles; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000972:Antineoplastic Agents, Phytogenic; D004396:Coloring Agents; D013778:Tetrazolium Salts; D013844:Thiazoles; D016685:Mitomycin; D004317:Doxorubicin; D003520:Cyclophosphamide; C022616:thiazolyl blue; D017239:Paclitaxel