UFT AND LEUCOVORIN - A REVIEW OF ITS CLINICAL DEVELOPMENT AND THERAPEUTIC POTENTIAL IN THE ORAL TREATMENT OF CANCER

UFT is an oral antineoplastic drug combining uracil and tegafur in a 4 :1 molar ratio. Tegafur acts as a prodrug of 5-fluorouracil (5-FU), be ing slowly metabolized by cytochrome P450 to 5-FU. UraciI competitivel y inhibits the metabolism of 5-FU, resulting in increased plasma and t umor 5-FU concentrations. At equimolar doses, higher peak plasma 5-FU concentrations are achieved with UFT plus oral leucovorin with similar systemic 5-FU exposure compared with low-dose continuous 5-FU infusio ns. The elimination half-life of 5-FU following UFT administration is approximately 7 h compared with 0.2 h with i.v. 5-FU. In phase II stud ies of UFT plus oral leucovorin for the treatment of advanced colorect al cancer, response rates ranged from 25 to 42%. UFT plus oral leucovo rin is well tolerated, with manageable diarrhea being the only dose-li miting toxicity; the regimen is not associated with significant myelos uppression, mucositis, hand-foot syndrome or alopecia, UFT, with or wi thout leucovorin, has also been evaluated alone or in combination with other cytotoxic agents for the treatment of advanced lung, breast and gastric cancers. UFT has also been evaluated as adjuvant therapy for colorectal, breast, gastric, head and neck, and superficial bladder ca ncers. UFT plus leucovorin offers patients an entirely oral cancer tre atment, and appears to provide potential advantages over bolus 5-FU re gimens with regard to toxicity and convenience of administration, Thes e benefits should be advantageous in the adjuvant setting, as well as in advanced disease settings in which palliation is an important consi deration. Ongoing clinical trials will further define the role of this promising oral treatment regimen. [(C) 1998 Lippincott-Raven Publishe rs.].