Multidrug combination in cancer chemotherapy: MFU therapy.
Three-drug therapy with Mitomycin-C (MMC), 5-fluorouracil (5-FU), and a nitrosourea derivative, ACNU, was carried out in 72 cases of carcinoma patients, mostly of stomach carcinoma. 1) According to Karnofsky's criteria, an effect of above I-A was observed in 10 of 35 cases (29%) treated with MFU-I (0.08 mg/kg of MMC, 10 mg/kg of 5-FU and 0.4-0.8 mg/kg of ACNU twice a week for the first two weeks and once a week thereafter for a total of six weeks as one course), 5 of 14 cases (36%) with MFU-I-O (MFU-I plus 0.2-2.0 KE of OK-432 i.m. three times a week), and 6 of 20 cases (30%) with MFU-II (0.2 mg/kg of MMC once in two weeks, 5 mg/kg of 5-FU every day, 2 mg/kg of ACNU once in six weeks as one course). 2) According to the criteria of the group of Grant-in-Aid for Cancer Research from the Ministry of Health and Welfare, a partial response was seen in 29% of the cases treated with MFU-I, in 38% of the cases treated with MFU-I-O, and 30% of the cases treated with MFU-II. 3) Side effect was slight in the digestive organs but the bone marrow suppression was remarkable. Leukopenia and thrombocytopenia were seen in the majority of patients under treatment. The hematological side effect appeared early in MFU-II therapy, but it was not severe and recovered quickly. Combined use of OK-432 seemed to be effective to shorten the period of hematological disorders. Thus, three-drug combination treatment with MMC, 5-FU, and ACNU seems to be useful for patients with malignant tumor, chiefly of the digestive organs. Especially, MFU-II treatment schedule seems to be a combination therapy that has relatively small hematological side effects.