SYNERGISTIC EFFECT OF METHIONINE-DEPLETING TOTAL PARENTERAL-NUTRITIONWITH 5-FLUOROURACIL ON HUMAN GASTRIC-CANCER - A RANDOMIZED, PROSPECTIVE CLINICAL-TRIAL

Methionine-depleting total parenteral nutrition (Met-depleting TPN), i nfusing AO-90 amino acid solution (lacking both L-methionine and L-cys teine) as a sole nitrogen source, showed synergistic effects with J-fl uorouracil (5-FU) in tumor-bearing rats and in clinical trials with ga strointestinal tract cancers. In this study, the effect of Met-depleti ng TPN with 5-FU upon thymidylate synthase (TS) activity was examined, and the histological effect of this treatment on human gastric cancer was evaluated. Fourteen preoperative advanced gastric cancer patients were divided randomly into two groups, Seven cases were given Met-dep leting TPN for 7 days before surgery with continuous intravenous admin istration of 5-FU (500 mg/body per day; total 4.0 g/body) (AO-90 group ). The other 7 received conventional L-methionine-containing TPN with 5-FU (control group). All patients underwent gastrectomy without compl ications due to these treatments. Resected materials were examined for TS kinetics, and the anti-cancer effect was also assessed histopathol ogically. The specimens in the AO-90 group showed marked degeneration of cancer, while almost no effect was seen in the control group. The f ree TS activity of carcinoma tissue in the AO-90 group was decreased a nd the TS inhibition rate was increased in comparison with the control group (P=0.0165 and P=0.0243, respectively). Met-depleting TPN appear s to play a role as a biomodulator of 5-FU in human gastric cancer.