Purpose: To evaluate the efficacy and toxicity of docetaxel in combination with a novel oral 5-fluorouracil analogue S-1for patients with advanced or recurrent gastric cancer. Experimental Design: Patients with advanced or recurrent adenocarcinoma of the stomach and up to one previous chemotherapy regimen were treated with i.v. docetaxel 40 mg/m 2 on day 1and oral S-1 80 mg/m 2 /d on days 1to 14 every 3 weeks. Results: Forty-eight patients (median age, 65 years; range, 25-75 years) received a total of 272 treatment cycles (median, 4; range, 1-17). No complete responses and 27 partial responses were observed for an overall response rate of 56.3% [95% confidence interval (95% CI), 38-66%]. Eighteen patients (37.5%) had stable disease and three patients (6.3%) had progressive disease as best response. The tumor control rate (complete response + partial response + stable disease) was 93.8% (95% CI, 83-98%). Median overall survival was 14.3 months (95% CI, 10.7-20.3 months) and median time to tumor progression was 7.3 months (95% CI, 4.3-10.0 months). The most common grade 3 to 4 hematologic toxicities were neutropenia (58.3 %), leukopenia (41.7%), febrile neutropenia (8.3%), and anemia (8.3%). The most common grade 3 nonhematologic toxicities included anorexia (14.6%), stomatitis (8.3%), and nausea (6.3%). No grade 4 nonhematologic toxicities were reported and all treatment-related toxicities were resolved. Conclusion: Docetaxel/S-1combination is highly active and well tolerated in advanced or recurrent gastric cancer. Further investigation in randomized studies is warranted.The prognosis for patients with unresectable advanced or recurrent gastric cancer is extremely poor; indeed, gastric cancer is the second most frequent cause of cancer-related mortality worldwide, accounting for f700,000 deaths annually (1). Several novel chemotherapeutic agents, including the taxanes (paclitaxel and docetaxel), irinotecan, and, more recently, oxaliplatin, S-1, and capecitabine, have shown activity in gastric cancer and offer hope for improving patient outcomes in this setting (2, 3). Response rates of up to 65% were reported in phase II studies of regimens, including taxanes, irinotecan, or oxaliplatin, and, consequently, several combinations have been investigated in randomized phase II/III studies (3).Docetaxel has shown promising activity in gastric cancer, both as monotherapy (4, 5) and in combination with other agents (6 -8). In the phase III TAX 325 study, triple-agent therapy with docetaxel-cisplatin-5-fluorouracil (5-FU; TCF) was superior to cisplatin-5-FU in terms of response rate (37% versus 25%; m 2 , P = 0.0106), time to progression (TTP; 5.6 months versus 3.7 months; risk reduction 32%; log-rank P = 0.0004), and survival (risk reduction 23% after a median follow-up of 23 months; log-rank P = 0.0201) in patients with metastatic gastric cancer (7). However, grade 3 to 4 treatment-emergent adverse events (regardless of relationship to study medication) occurred in 81% and 75% of patients receiving TCF and cis...