Kubota T, Matsuzaki S W, Hoshiya Y, Watanabe M, Kitajima M, Asanuma F, Yamada Y, Koh J I
Department of Surgery, School of Medicine, Keio University, Tokyo, Japan.
J Surg Oncol. 1997 Feb;64(2):115-21. doi: 10.1002/(sici)1096-9098(199702)64:2<115::aid-jso5>3.0.co;2-e.
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.
Paclitaxel at 20 mg/kg dissolved in 0.2 ml ethanol/cremophor EL solution was administered intraperitoneally daily for 5 days.
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.
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.