EFFECTIVENESS OF INTERMEDIATE-DOSE METHOTREXATE AND HIGH-DOSE 5-FLUOROURACIL AS SEQUENTIAL COMBINATION CHEMOTHERAPY IN REFRACTORY BREAST-CANCER AND AS PRIMARY THERAPY IN METASTATIC ADENOCARCINOMA OF THE COLON

Abstract

Many studies reported that pretreatment with methotrexate followed by 5-FU [5-fluorouracil] resulted in the greatest tumor cell killing. The possibility of drug synergism in the [mouse leukemia] L1210 cell line, but not in human bone marrow cells, was confirmed. Thirteen patients with metastatic adenocarcinoma of the breast and 7 patients with metastatic adenocarcinoma of the colon were treated with an innovative approach in which methotrexate preceded 5-FU administration in an attempt to cause drug synergism and prevent drug antagonism. All patients with breast cancer and 2 patients with colon cancer had been extensively pretreated with multiple drugs. Of the cancer patients so treated, 3 (23%) with breast cancer and 2 (28%) with colon cancer demonstrated objective tumor response. In addition to these patients, 6 (46%) with breast cancer and 3 (43%) with colon cancer demonstrated subjective improvement as manifested by total pain relief and reduction in CEA [carcinoembryonic antigen] titer. Sequential utilization of intermediate doses of methotrexate, followed by high doses of 5-FU, probably is an effective combination chemotherapy for patients with breast and colon malignancies.