Antitumor effect of docetaxel against human endometrial tumor cell lines

摘要

The antitumor effect of docetaxel against human endometrial tumor cell lines was investigated in vitro and in vivo. In the in vitro study,docetaxel showed concentration-dependent inhibition of the growth of 4 tumor cell lines having different degrees of differentiation (AN3 CA, KLE, HEC-1-A and HEC-1-B), with IC(50) values ranging from 2.48 to 82.40 ng/ml. These values represent ca. 1/900-1/30 of the mean maximum plasma concentration of 2.27 microg/ml attained when the recommended dose of 70 mg/m(2) for patients with endometrial cancer was administered to patients with various types of cancer in phase I trial. In addition, the activity was nearly equal to paclitaxel, and much more potent than fluorouracil, cisplatin and doxorubicin. Docetaxel also showed strong antitumor activity against xenografts of the AN3 CA human endometrial adenocarcinoma cell line in nude mice. In the docetaxel treated group at its MTD (33 mg/kg/dose, q 6 d x 3, iv), all of the animals were tumor-free survivors on Day 62 after xenografting. The antitumor effect in the MTD-administered group was the strongest of all of the tested anticancer drug groups (cyclophosphamide, mitomycin C, fluorouracil, cisplatin, doxorubicin). Even at two docetaxel dosages below its MTD (20.5 and 12.5 mg/kg/day), the drug showed a marked cytotoxic activity. These results demonstrated that docetaxel shows potent antitumor efficacy against human endometrial tumor cell lines, leading to the expectation that it will be useful as a therapeutic agent for endometrial cancer.