Systemic Chemotherapy in Gastric Cancer: Where Do We Stand Today?

Gastric cancer is one of the major causes of cancer-related mortality worldwide. Its prognosis is poor, and surgery offers the only realistic chance of cure. Nevertheless, most of the patients present with inoperable tumors, while the recurrence rate after potentially curable resections is high. In these patients, systemic chemotherapy has been used for palliation of symptoms and possibly for prolongation of survival. 5-fluorouracil (5-FU) is the most widely used agent in chemotherapy of gastric cancer alone or combined with other cytotoxic drugs. Until recently, combination chemotherapy produced modest results, with no significant impact on survival. Progress in research studying the mechanisms of action of various chemotherapeutic agents led to the design of more active chemotherapy regimens. Combinations of 5-FU and cisplatin and the use of modulators of 5-FU activity have produced high response rates, including complete responses in more than 10% of patients with advanced gastric cancer, and, in certain studies, a small but significant survival benefit over older regimens. Adjuvant chemotherapy has not generally produced a significant survival benefit in patients undergoing curative resection. The use of newer, more effective regimens is currently being investigated and might prove useful in certain high-risk groups. Neoadjuvant chemotherapy, chemoradiotherapy, and chronomodulated administration of 5-FU, along with the use of novel chemotherapeutic agents, represent exciting areas for clinical research which might further improve the role of systemic chemotherapy in gastric carcinoma.