Treatment of peritoneal dissemination of gastric cancer with sequential methotrexate and 5-fluorouracil

Background. Pretreatment with methotrexate (MTX) followed by 5-fluorouracil (5-FU) (sequential MTX and 5-FU), exerts biochemical modulation in which the antitumor effect of 5-FU is enhanced by the preceding MTX. Since the early 1980s, the sequential MTX/5-FU regimen has been employed clinically for gastric cancer in Japan, with high response rates for undifferentiated type gastric carcinoma. Methods. Peritoneal dissemination is more frequent in undifferentiated type carcinoma, we therefore employed sequential MTX and 5-FU for the treatment of 39 gastric cancer patients with peritoneal dissemination. We also investigated MTX levels in blood and ascitic fluid during the treatment. Results. Partial response (PR) was achieved in 6 of 26 patients (23%) who had evaluable lesions. PR lesions included abdominal wall tumors, primary gastric foci, inguinal lymph node, and rectal stenosis. Ascites was eliminated in 50% of the patients, and pleural effusion disappeared in 2 patients. Conclusions. In our study, sequential MTX and 5-FU had low toxicity and was beneficial for advanced gastric cancer patients with peritoneal dissemination. Further investigation of this treatment as induction and postoperative adjuvant chemotherapy for Borrmann type 4 gastric cancer seems warranted. Received for publication on Feb. 8, 1999; published on March 15, 1999