Advances in the therapy of gastric cancer.

Many issues remain unclear in the management of gastric cancer. Randomized trials have failed to show the superiority of D2 over D1 dissection, and comparisons between countries showing higher survival rates following more extensive surgery may be influenced at least in part by the fact that D1 dissection underestimates disease stage in many patients. No studies have yet shown a benefit from adjuvant chemotherapy. However, the Southwest Oncology Group (SWOG) 9008 trial provides convincing evidence that a regimen of postoperative 5-fluorouracil (5-FU)-based chemoradiotherapy improves disease-free and overall survival when compared with observation alone. In the chemotherapy of advanced disease, use of the epirubicin plus cisplatin plus 5-FU (ECF) regimen leads to significantly longer median survival than 5-FU plus adriamycin plus methotrexate-C (FAMTX), but the rate of complete response remains low and the effect on longterm survival minimal. There are indications that neoadjuvant chemotherapy may increase the resectability of tumors and reduce risk of postoperative recurrence. Substantial improvements in outcome are likely to depend on the integration into multimodality strategies of novel, molecularly targeted agents in all stages of gastric cancer treatment.