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.

Many studies reported the pretreatment with methotrexate followed by 5-FU resulted in the greatest tumor cell killing. Our preliminary laboratory studies confirmed the possibility of drug synergism in the L1210 cell line, but not in human bone marrow cells. Thirteen patients with metastatic adenocarcinoma of the breast and seven 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 two patients with colon cancer had been extensively pretreated with multiple drugs. Of the cancer patients so treated, three (23%) with breast cancer and two (28%) with colon cancer demonstrated objective tumor response. In addition to these patients, six (46%) with breast cancer and three (43%) with colon cancer demonstrated subjective improvement as manifested by total pain relief and reduction in CEA titer. The preliminary results reported in this study suggest that sequential utilization of intermediate doses of methotrexate, followed by high doses of 5-FU, is an effective combination chemotherapy for patients with breast and colon malignancies.