Taking into account the substantial doubts concerning the potential benefit of postoperative part in the perioperative chemotherapy regimen we designed a study assessing value of this approach in gastric cancer. To improve compliance with a protocol regimen of this aggressive combined therapy we replaced tested in the MAGIC trial ECF regimen with more effective and better tolerable EOX chemotherapy regimen. The value of postoperative three-cycle EOX regimen will be tested in patients with locoregionally advanced gastric cancer with positive pathological response to preoperative three-cycle EOX chemotherapy regimen. The patients will be randomized to the postoperative chemotherapy or to the follow-up arm.

The MAGIC trial, also considered the "milestone" study, definitely proved that neoadjuvant chemotherapy improves the outcome of patients with locally advanced gastric cancer. Resection was considered curative in 79% under combination therapy versus in 69% of only operated patients (P = 0.02), 2-year survival rates were 50 and 41%, and 5-year-survival rates were 36 and 23% (P = 0.009), respectively. The substantial weak point of the MAGIC trial remains the fact that only about 40% of the patients received the full dosage of scheduled postoperative chemotherapy, mainly due to intolerance or toxicity reasons.

The noninferiority in relation to survival of capecitabine to 5-FU in triplet regimens for the treatment of patients with advanced esophagogastric cancer was demonstrated in the large multicenter randomized phase III, REAL-2 study, including 1002 patients. Capecitabine has overcome the doubts concerning the potential efficacy of oral drug administration in patients with gastric carcinoma, especially in relation to those patients who have undergone partial or total gastrectomy. The same study demonstrated the noninferiority of oxaliplatin versus cisplatin in advanced gastric cancer and confirmed the acceptable tolerability profile of this third-generation platinum analogue. It was anticipated that the use of these newer agents as components of triplet regimens would reduce toxicity and thereby render an alternative to the standard ECF combination easier to handle as a consequence of replacing the cisplatin component with oxaliplatin, replacing the infusional 5-fluorouracil component with oral capecitabine in EOX regimen. Furthermore, achieving a median overall survival time of 11.2 months, the EOX regimen appeared to be more active than ECF (median overall survival time, 9.9 months), with the higher 1-year survival rate 47% vs 38%, respectively. Compared with the ECF regimen, EOX was associated with significantly lower rates of grade 3 or 4 neutropenia and grade 2 alopecia, but significantly higher rates of grade 3 or 4 lethargy, diarrhea, and peripheral neuropathy. Based on the results of the REAL study, EOX is therefore tolerable, and at least as active as ECF. This modified regimen could therefore be considered to be a new standard treatment and may be an appropriate reference regimen for future studies in advanced gastric cancer.

Inclusion Criteria:

• histopathologically confirmed gastric cancer
• potentially resectable, local or locoregional cancer with clinical staging cT2-4aN0-3M0. A clinical assessment of location, resectability and staging will be performed based on endoscopy, barium swallow, endoscopic ultrasound, multidetector computed tomography and diagnostic laparoscopy with cytology washing.
• medically fit to undergo a major abdominal surgery and in general condition allowing to tolerate long-lasting chemotherapy (Karnofsky Performance Status ≥70, ECOG 0-1)

Exclusion Criteria:

• Pregnancy or breast feeding.
• Diagnosed other malignancy and/or chemotherapy administrated within the last 5 years
• Gastric remnant cancer;
• Early Gastric Cancer;
• Irresectable or disseminated cancer with distant organ metastases and/or peritoneal spreading and/or positive cytology washing
• Poor performance status measured by Karnofsky index < 60 or ECOG < 1
• Clinically important active systemic disease: unstable diabetes, circulatory failure of NYHA III or IV, unstable arterial hypertension, unstable coronary heart disease, recent heart infarct or brain insult within the last 6 months, severe COPD, peripheral neuropathy of grade 2-4;
• Severe hematological abnormalities: HGB < 10.0 gm/dL and/or neutropenia < 1500 /mm3; PLT < 100 000 /mm3.
• Severe renal dysfunction requiring peritoneal dialysis, hemodialysis or hemofiltration or oliguria <20ml/h.
• Severe liver dysfunction: acute or chronic hepatitis, liver cirrhosis, liver failure, abnormal liver testing: ALAT or ASPAT or ALP >2.5 - 5.0 × upper limit; total bilirubin >2 x upper limit.
• Concommitant infection