BACKGROUND: Despite recent developments in chemotherapeutic trials, the long-term results of chemotherapy remain to be clarified. We evaluated the impact of chemotherapy on long-term survival in patients with unresectable gastric cancer.METHODS: Between 1985 and 1991, a total of 363 patients with gastric cancer were enrolled into a single randomized phase II study and into three series of phase II studies of the Japan Clinical Oncology Group. The chemotherapy regimens consisted of tegafur + mitomycin C (FTM), uracil-tegafur + mitomycin C (UFTM), 5'deoxy-flurorouridine + cisplatin (5'P), etoposide + doxorubicin + cisplatin (EAP), and 5-fluorouracil + cisplatin (FP). After a review of the 363 patients' case records, 226 patients who fulfilled the criteria of having "unresectable" factors prior to chemotherapy became the subjects for this analysis. Of the 226 patients, 50 were in the FTM regimen group, 39, in the UFTM; 49, in the 5'P; 42, in the EAP; and 46, in the FP group. Survival was updated continually.RESULTS: Of the 226 patients, 22 (10%) survived longer than 2 years, and 8 (4%) have survived longer than 5 years. The 8 5-year survivors consisted of 6 patients who had para-aortic node metastases alone as an "unresectable factor", 1 who had para-aortic and cervical node metastases, and the remaining patient who had liver metastasis alone. Twenty-nine patients with para-aortic node metastasis alone had a significantly longer survival than the other 197 patients ( P < 0.001).CONCLUSION: Systemic chemotherapy may offer some hope of achieving long-term survival in patients with unresectable gastric cancer, particularly when the patient has metastasis only to para-aortic nodes.