Background: Fluorouracil and platinum can be considered a standard option for advanced gastric cancer (AGC). Docetaxel is also an effective agent with no cross-resistance with fluorouracil and platinum. Concomitant combination of docetxel with fluorouracil and platinum had been explored, but demonstrated intolerable toxicities. A different way to include all active agents in first-line treatment of gastric adenocarcinoma may be to use them sequentially. We aimed to evaluate the activity and the safety profile of sequential chemotherapy with capecitabine plus oxaliplatin followed by docetaxel plus capecitabine in the first-line treatment of AGC. Methods: We conducted a phase II study of first-line sequential chemotherapy in AGC. Treatment consisted of 6 cycles of capecitabine plus oxaliplatin (XELOX, Capecitabine 1000 mg/m² bid on day 1-10 and Oxaliplatin 85 mg/m² on day 1, Q2W) followed by 4 cycles of docetaxel plus capecitabine (TX, Docetaxel 30 mg/m² on D1 and D8, Capecitabine 825 mg/m² bid on day 1-14, Q3W). Primary end-point was the objective response rate. Results: Fifty-one patients were enrolled: median age 63 years; Male/Female: 37/14. Main grade 3-4 toxicities were ANC decreased (25.5%), diarrhea (11.8%), hand-foot syndrome (15.7%) and anemia (11.8%). The objective response rate was 56.9%. Median PFS and OS were 8.6 and 10.8 months, respectively. Five patients (9.8%) received surgery after chemotherapy and four were still on disease-free status. Conclusions: This sequential treatment demonstrated feasibility with a favorable safety profile and produced encouraging results in terms of activity and efficacy. Clinical trial information: NCT01558011