Background: S-1 in combination with cisplatin is one of several accepted doublets, but triplet combinations with docetaxel (D) increase efficacy and substitution with oxaliplatin (O) and oral fluoropyrimidines (S-1) ease the administration. Based on our recent phase I study, we wanted to establish a recommended dose (RD) for an every 3 week regimen (DOS_3w) but inspired by promising data from the GATE study, we also sought for an every second week regimen (DOS_2w). Therefore we designed this dose-finding study which present the first experience with the combination of D+O+S-1 (DOS) in Caucasian patients (Clinical trial ID: 2011-003471-11). Methods: All pts had chemo-naïve aGEA. We used a standard 3+3 phase I design. DOS_2w (dose levels 1A-4A) was given with escalating doses of D (30 to 50 mg/m² day 1) and S-1 (2x30 to 2x35 mg/m²/day - days 1-7) with a fixed dose of O (70 mg/m²day 1) every 2 weeks for a maximum of 9 cycles. DOS_3w (dose levels 1B-3B) was given with escalating doses of D (40 to 60 mg/m² day 1) and fixed doses of O (100 mg/m² day 1) and S-1 (2x25 mg/m²/day - days 1-14 every 3 weeks) for a maximum of 6 cycles. After the planned number of DOS, S-1 maintenance therapy (2x30 mg/m²days 1-14 every 3 weeks) was administered until PD or toxicity. Toxicity was evaluated according to NCIC-CTC 4.0. Dose-limiting toxicity (DLT) was evaluated after the first course of DOS and defined as non-hematological toxicity grade ≥ 3 or febrile neutropenia. RD was defined as the highest level at which less than 2/6 of pts experienced a DLT. Once RD was established, this level was expanded to at least 6 pts. Results: From Oct. 2013 to Mar. 2015, 18 and 16 patients received DOS_2w and DOS_3w, respectively. Median age was 63 years (49-78). DLTs in both cohorts were febrile neutropenia. Response rates were 56% and 57% and OS were 13.8 and 11.6 months, respectively. Conclusions: We recommend DOS_2w at dose level 3A (D 40 mg/m² day 1; O 70 mg/m² day 1 and S-1 2x35 mg/m²/day orally days 1-7 every 2 weeks) and DOS_3w at dose level 2B (D 50 mg/m² day 1; O 100 mg/m² day 1 and S-1 2x25 mg/m²/day orally days 1-14 every 3 weeks). Both regimens are well-tolerated in an out-patient setting. Clinical trial information: 2011-003471-11.