Status of newer chemotherapeutic strategies for the treatment of metastatic gastric cancer

The role of chemotherapy in advanced gastric and gastroesophageal junction cancers is evolving. Although there is no established global front-line treatment regimen, combination therapy with fluorouracil and cisplatin is often used as first-line therapy in untreated patients with advanced disease. Reference regimens vary depending on regional and cultural preferences. In the last 5 years, there has been increased enthusiasm for newer agents used as monotherapy or in combination. These agents include camptothecins, notably irinotecan, taxanes oxaliplatin, and the novel oral fluoropyrimidine S-1. Modest activity has been observed with these drugs as single agents with objective responses in the range of 12-20% and slightly higher for S-1. Combination regimens with two or three agents have resulted in higher response rates (in the range of 30-50%). However, this it at the expense of increased toxicity; the toxic effects have varied depending on the class of drugs combined. With improving clinical trial designs and the availability of a larger number of newer agents, the challenge to establish new combinations and new paradigms that improve the outcome of patients with advanced gastric and gastroesophageal cancers continues. The future offers a greater understanding of pharmacogenomics and molecular biology that will help identify better therapeutic targets. When possible, all eligible patients with metastatic gastric or gastroesophageal cancer should be enrolled in a clinical trial.