Sequential Methotrexate and 5-Fluorouracil in Advanced Gastric Cancer

Toshiro Konishi, Ken-ichi Mafune, Mamoru Hiraishi, Takeshi Miyama, Toru Hirata, Junji Yoshida, Kiyoshi Mori, Yasuo Idezuki

The Second Department of Surgery, Faculty of Medicine, University of Tokyo

Biochemically modulated chemotherapy preceded by administration of methotrexate (MTX) and followed by 5-fluorouracil (5-FU) was given to 40 patients with advanced grastric cancer. The standard procedure was weekly intermediate-dose therapy consisting of MTX 100 mg/m² (i.v.) followed one hour later by 5-FU 800 mg/m² (i.v.) with leucovorin rescue in the following two days with concomitant OK-432 administration, but low-dose therapy of MTX 30 mg/m² and 5-FU 600 mg/² was an alternative for 9 ambulatory patients. Of the 29 evaluable patients, 7 showed a partial response to the treatment (response rate 24%). Although none of the well differentiated group patients responded to this treatment, the response rate in the poorly differentiated group was as high as 35%. Seven responders and 5 other minorly improved patients showed the histological characteristics of poorly differentiated adenocarcinoma. In addition, effusion in the abdominal or pleural cavity caused by dissemination of the poorly differentiated adenocarcinoma was markedly improved in 8 of 12 patients by the treatment, retaining the relatively high serum MTX level after the intermediate-dose therapy. The rationale of this treatment for patients with poorly differentiated gastric cancer including those with malignant effusion in the pleural or abodminal cavitv was revealed here.

Key words
sequential methotrexate and 5-fluorouracil, advanced gastric cancer, poorly differentiated adenocarcinoma, serum MTX level, malignant effusion

Reprint requests
Toshiro Konishi The Second Department of Surgery, Faculty of Medicine, University of Tokyo
7-3-1 Hongo, Bunkyo-ku, Tokyo, ll3 JAPAN

Accepted
April 11, 1990

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