ANTITUMOR-ACTIVITY OF PACLITAXEL AGAINST HUMAN BREAST-CARCINOMA XENOGRAFTS SERIALLY TRANSPLANTED INTO NUDE-MICE

Background: Paclitaxel (RMS-181339: Taxol) is a promising agent agains t previously treated breast cancer. The antitumor activity of paclitax el was evaluated using five human breast carcinoma xenografts in nude mice, Methods: Paclitaxel at 20 mg/kg dissolved in 0.2 mi ethanol/crem ophor 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 xenogra fts (R-27, Br-10, and T-61), suggesting its substantially different an titumor spectrum from conventional antibreast cancer drugs, The differ ent sensitivity of xenografts to paclitaxel was successfully reproduce d in vitro using the MTT assay, when the cutoff concentration of pacli taxel was 20 mu g/ml. Conclusion: Since no significant differences wer e observed in the pharmacokinetics of paclitaxel in sensitive and resi stant tumor cell lines, the efficacy of this agent seemed to depend on the sensitivity of tumor cells rather than the intratumoral concentra tion of agent. (C) 1997 Wiley-Liss, Inc.