[Augmentation of chemotherapeutic efficaciousness of UFT by oral l-leucovorin--growth-inhibitory activity of combination against human tumor xenograft].

Combination chemotherapy with FUra and LV has been reported as a useful treatment for patients suffering from colon carcinoma. Usually, both FUra and LV are administered by intravenous infusion, but not orally. UFT, an anti-neoplastic agent consisting of FT and uracil, is widely used for oral administration in Japan. Using human tumor xenografts of 10 cell lines, we evaluated the efficacy of UFT combined with l-LV, which is the active form of LV, by oral administration. Combined treatment of UFT with l-LV was more effective than UFT alone on the growth suppression of colon carcinoma (KM 20 C, Col-1) and mammary carcinoma (H-31, MX-1). When 1.85 mg/kg (5.55 mg/m2) of LV was given to tumor bearing mice, the antitumor activity of UFT was augmented and at a dose of 5.56 mg/kg (16.7 mg/m2) of LV, it was significantly augmented. Among various 5-FU derivatives, such as UFT, 5'-DFUR or FUra, combined treatment using UFT with l-LV was the most effective by oral administration. l-LV did not improve the anti-tumor efficacy or toxicity of 5'-DFUR. l-LV seemed to augment the anti-tumor activity of FUra, but not significantly. These results suggest that combination chemotherapy of UFT with LV is a promising approach for the clinical treatment of human colon cancer.