Clinical basis of chemotherapy for gastric cancer with uracil and 1-(2′-tetrahydrofuryl)-5-fluorouracil

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Abstract
Studies were performed on the clinical basis of chemotherapy for human cancer with uracil and l-(2′-tetrahydrofuryl)-5-fluorouracil (FT). In 62 operated patients with stomach, breast, and uterine cancers, the concentration of 5FU and FT were compared in serum, tumor and normal tissues 1, 2, 4, 6, 8, and 12 hours following the administration of 300 mg of UFT (300 mg of FT plus 672 mg uracil, a uracil/FT molar ratio of 4), or FT alone. It was found that the level of 5-FU in tumor tissue remained above 0.05 mcg/g over 12 hours. This value for 5-FU corresponds to a minimum inhibitory concentration in thein Vitro experiment with L1210 cells. Blood levels of 5-FU increased up to 0.1 mcg/ml 1 hour after UFT administration and then decreased below 0.05 mcg/ml. The drug concentration in normal tissues was lower than that of the tumor tissues. On the basis of the above findings and phase I study, a protocol of UFT-therapy was made and applied for the treatment of gastric cancer. Our patients were given an oral dose of 300 mg of UFT twice a day per 50 kg body weight (12 mg/kg BW). Therapeutic effects were detectable in 7 of 20 cases. In addition, a combination of mitomycin C (6 mg i.v. weekly) with UFT seemed to improve the response rate (5/7). Diarrhea (15%) and skin pigmentation (10%) were major side effects of UFT.