[Antitumor effect of docetaxel against human esophagus tumor cell lines and tumor xenografts in nude mice].
The antitumor effect of docetaxel against cultured human esophagus tumor cell lines and tumor xenografts in nude mice was investigated. In the in vitro study, docetaxel showed concentration-dependent inhibition of the growth of 4 tumor cell lines having different degrees of differentiation (T. T, TE-5, TE-9 and TE-15) with IC(50) values ranging from 0.84 to 1.68 ng/ml when exposed for 72 h. These values represent ca. 1/2,700-1/1,400 of the mean maximum plasma concentration of 2.27 microg/ml attained in the clinical setting. In addition, the activity was found to be ca. two-fold stronger than that of paclitaxel, and much more potent than fluorouracil and cisplatin. The in vivo antitumor effect of docetaxel was also investigated against xenografts of human esophagus squamous cell carcinoma H-190 (highly differentiated) and H-204 (moderately differentiated) in nude mice. Docetaxel at its Maximum Tolerated Dose (MTD) and the lower dose (4.5, 6.7 mg/kg/dose, q 4 d x 3, iv) showed a significant growth inhibition of ca. 100% against H-190 tumor, resulting in the tumor shrinkage. Paclitaxel (6.7, 10 mg/kg/dose, q 4 d x 3, iv) showed a tumor-shrinking effect similar to that seen with docetaxel. In the H-204 xenograft model, docetaxel (4.5, 6.7, 10 mg/kg/dose) exhibited a dose-dependent effect in delaying the tumor growth, while paclitaxel failed to suppress the tumor growth even at its MTD. These results demonstrated that docetaxel has potent antitumor efficacy against human esophagus tumor cells, leading to the expectation that it will be useful as a therapeutic agent for esophagus cancer.
Drug Safety Evaluation, Preclinical Development, Scientific Affairs, sanofi-aventis K.K.
Shuji
S
Shakuto
Fumiko
F
Fujita
Masahide
M
Fujita
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology* / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D000077143:Docetaxel; D004334:Drug Administration Schedule; D004938:Esophageal Neoplasms / Q000473:pathology*; D005472:Fluorouracil / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D020128:Inhibitory Concentration 50; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D017239:Paclitaxel / Q000494:pharmacology; D043823:Taxoids / Q000494:pharmacology* / Q000627:therapeutic use; D014183:Transplantation, Heterologous
D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D043823:Taxoids; D000077143:Docetaxel; D017239:Paclitaxel; D002945:Cisplatin; D005472:Fluorouracil