OBJECTIVE Due to the recent development of several promising chemotherapeutic agents, such as S-1, irinotecan (CPT-11) and paclitaxel, response rates for advanced gastric cancer to chemotherapy have improved. Thus far, however, the efficacy and survival benefits of sequential chemotherapy using these agents have not been evaluated. An additional benefit of outpatient sequential chemotherapy, that is, without hospitalization, would be its contribution to the maintenance of patients' social activities. The aim of this study was to retrospectively evaluate sequential outpatient chemotherapy for advanced gastric cancer. METHODS Patients with metastatic/recurrent gastric cancer treated with sequential outpatient chemotherapy were analyzed retrospectively. The sequential treatment consisted of S1-based chemotherapy as first-line therapy, low-dose CPT-11/CDDP as second-line therapy and weekly paclitaxel administration as third-line therapy. RESULTS A series of 32 patients was enrolled in this study. During the sequential chemotherapy, all patients were treated at the outpatient ward of Kyoto University Hospital without hospitalization. The overall response rate was 37.5% and the median survival time was 523 days (95% confidence interval: 323-723 days). The progression-free survival for the three therapies was 135 days for S-1, 148 days for low-dose CPT-11/CDDP and 57 days for paclitaxel. Grade 4 neutropenia was observed in 1 patient (3.1%), and there were no treatment-related deaths. Univariate analysis showed that factors with significant impact on survival were pathological type (intestinal vs. diffuse), clinical response (responder vs. non-responder) and prior chemotherapy. Factors with p values <0.1, including pathological type, clinical response, prior chemotherapy and age (>75 vs. < or =75 years), were evaluated by multivariate analysis, which disclosed that clinical response and patient age were significantly related to patient prognosis. CONCLUSIONS In terms of survival and maintenance of social activities of patients, outpatient sequential chemotherapy appears to be both feasible and effective for advanced gastric cancer. Although prospective analysis of sequential chemotherapy is difficult because of its complex treatment protocol, clinical trials to assess the survival benefits of second-line chemotherapy for advanced gastric cancer are clearly warranted.