Docetaxel alone or orally combined with 5-fluorouracil and its derivatives: effects on mouse mammary tumor cell line MM2 in vitro and in vivo

Although docetaxel (Taxotere; TXT), a taxoid anticancer drug, is clinically and experimentally very effective against breast cancer, its antitumor eff ect is of very short duration. We addressed whether 5-fluorouracil (5-FU) a nd its derivatives can act synergistically with TXT against mammary tumors, with placing particular stress on their use by oral route. Mouse mammary t umor cell line, MM2, was propagated in culture and as ascites in mice. Carm ofur (HCFU) and doxifluridine (5'-DFUR) were used as 5-FU derivatives. In v itro, the cytotoxic effects of antitumor drugs on MM2 cells were examined b y MTS assay. In vivo, mice inoculated i.p. with MM2 cells were treated with i.p. injection of TXT and/or oral administration of 5-FU or its derivative s, and observed for curing tumor. In vitro, the synergistic effects were ob served in the combination of TXT and 5-FU or HCFU, but not in that of TXT a nd 5'-DFUR. In vivo, all of these combinations cured tumors far more effect ively than TXT alone. The discrepant result of the combination of TXT and 5 '-DFUR between in vitro and in vivo was ascribed to upregulation of pyrimid ine phosphorylase in tumor cells in vivo by TXT. Thus, 5-FU, its masked com pounds like HCFU and its prodrugs like 5'-DFUR can act synergistically with TXT in the therapy of cancer even when administered by the oral route. [(C ) 2001 Lippincott Williams & Wilkins.].