This study evaluated the efficacy, safety and impact on quality of life (QoL) of a dose-dense biweekly regimen of docetaxel and 5-fluorouracil in first-line treatment of advanced gastric cancer (AGC). Eligible patients received docetaxel 60 mg/m(2) and 5-fluorouracil (400 mg/m(2) bolus followed by 2,400 mg/m(2) 46-h infusion), fortnightly. Prophylactic use of G-CSF was adopted in all patients. The primary end point was response rate (RR). Secondary end points were progression-free survival (PFS), overall survival (OS), toxicity and QoL. Thirty-nine patients with a median age of 55 (28-80) were included. The RR was 51.3 %. Median PFS and OS were 6.7 and 14.0 months, respectively. The most common adverse events (all grades) were anemia (34, 87.2 %), fatigue (29, 74.4 %), neutropenia (26, 66.7 %), nail change (19, 48.7 %) and liver dysfunction (15, 38.5 %). In QoL analysis, improvements were obtained in seven scales, whereas drops were seen in three scales. Common Grade 3/4 toxicities included anemia (28.2 %), liver dysfunction (7.7 %) and fatigue (7.7 %). This novel regimen is a promising option for AGC, showing high RR, improvement on QoL and acceptable toxicity.