Objective: Prognosis of metastatic gastric cancer is poor and median survival is between 3 and 5 months. Response rates of combination chemotherapy with 5-fluorouracil (5-FU) and cisplatin in first-line treatment have been found to be 20-25% in the English literature. It has been demonstrated that adding docetaxel to combination chemotherapy improved time to progression and overall survival. However, the toxicity rates of the docetaxel-cisplatin-5-FU protocol were high. In our study we compared efficacy and toxicity of cisplatin-5-FU-folinic acid (CFF) and modified docetaxel-cisplatin-5-FU (mDCF) regimens in the first-line treatment of metastatic gastric cancer. Patients and Methods: Between June 2004 and October 2008, 70 patients with previously untreated metastatic gastric cancer treated with CFF (n = 30) and mDCF (n = 40) were retrospectively evaluated in the study. Survival and toxicity data were compared. Results: Median age of the patients was 53 years (range 23-69). Forty-eight percent of the patients were male and 75.7% had an ECOG performance status of 0-1. Prognostic factors including age, ECOG performance status, histopathological grade, and number and sites of metastases were similar between the groups. Objective response rates (complete and partial response) were higher in the mDCF group (30.0 vs. 13.3%, p = 0.19). While toxicity was acceptable in both groups, the most common grade 3-4 toxicities were anemia in 3.3 and 5.0%, neutropenia in 20 and 7.5%, febrile neutropenia in 6.7 and 5.0%, and diarrhea in 3.3 and 5.0% in the CFF and mDCF groups, respectively. Median follow-up was 10.3 (1.5-59.6) months. During that period 90 and 97.5% of the patients were dead in the CFF and mDCF groups, respectively. Median time to progression was 4.4 (95% CI 1.8-7.0) and 6.2 months (95% CI 5.6-6.8) (p = 0.85), median overall survival was 6.5 (95% CI 1.8-11.2) and 8.7 months (95% CI 6.7-10.7) (p = 0.88) in the CFF and mDCF groups, respectively. Conclusion: The mDCF regimen has been found to be more favorable than the CFF regimen with an acceptable toxicity profile in the first-line treatment of metastatic gastric cancer. Copyright © 2011 S. Karger AG, Basel.