Is there an optimal chemotherapy regimen for the treatment of advanced gastric cancer that will provide a platform for the introduction of new biological agents?

Globally, gastric cancer is the second most common cause of cancer-related death. The majority of gastric cancer patients will have at presentation or will ultimately develop overt metastatic disease. Meta-analysis has demonstrated not only that systemic chemotherapy can improve survival in patients with advanced disease but also that the best survival results in earlier randomized studies have been achieved with three-drug regimens containing a fluoropyrimidine, an anthracycline, and cisplatin. Although there has been little progress historically in improving median overall survival times beyond the 9-month plateau achievable with the standard epirubicin-cisplatin-infusional 5-fluoropyrimidine (ECF) combination, the availability of newer cytotoxic anticancer agents has provided some measure of optimism that current outcomes can be improved. A number of new triplet and doublet combinations incorporating docetaxel, oxaliplatin, irinotecan, capecitabine, and S-1 have been explored in randomized trials. Although some combinations, such as epirubicin-oxaliplatin-capecitabine, have been shown to be as effective as (or perhaps more effective than) ECF, and although promising early data have been derived for S-1 in combination with cisplatin, a lack of studies in which direct comparisons have been made currently hinders the identification of the optimal regimen in this setting. One factor that might contribute to the lack of clear progress is the absence of consensus on the utility of second-line cytotoxic treatments. It can therefore be concluded that, although there is no first-line regimen that is clearly the most appropriate platform for the investigation of biological agents, there are a number of combinations that have been shown to be effective and therefore good candidates.