Adjuvant mitomycin and fluorouracil followed by oral uracil plus tegafur in serosa-negative gastric cancer: a randomised trial

Background To study the survival benefit of adjuvant chemotherapy in gastric cancer, seven cancer centres in Japan carried out a phase III clinical trial of adjuvant chemotherapy after curative gastrectomy for macroscopically serosa-negative gastric cancer. Methods 579 patients were enrolled in the study, stratified by disease stage (T1, n=188; T2, n=323), and allocated randomly adjuvant chemotherapy or no further treatment, 285 of 288 cases in the treatment group and 288 of 291 in the control group were eligible, Six cases were excluded because they did not fulfil the entry criteria. The treatment group had intravenous mitomycin (1.4 mg/m(2)) and fluorouracil (166.7 mg/m(2)) twice weekly for 3 weeks after surgery, and oral UFT (uracil plus tegafur, 300 mg daily) for 18 months. Analyses were by intention to treat. Findings No serious toxic effects were observed in the treatment group. At median follow-up of 72 months, 59 patients in the control group and 47 in the treatment group had died. There was no significant difference in survival between the groups (5-year survival 82.9% control vs 85.8% treated; hazard ratio 0.738 [95% CI 0.498-1.093]). 5-year survival of patients with T1 (mucosal or submucosal) cancer in the control and treatment groups was 94.9% versus 92.0%, and that of patients with T2 (muscularis propria or subserosa) cancer was 76.9% versus 83.0%. However, a test for heterogeneity and interaction over T1 and T2 subgroups revealed no significant difference in terms of drug response. Interpretation There was no survival benefit with this adjuvant therapy regimen for patients with macroscopically serosa-negative gastric cancer (T1 and T2) after curative gastrectomy. Patients with T1 cancer can be excluded from future trials, because curative surgery alone yielded a very good survival rate and there seemed no need for adjuvant therapy.