Advanced gastroesophageal carcinoma: an update on the current therapeutic landscape

Abstract

Gastroesophageal cancers are usually diagnosed in an advanced stage, and effective treatment options remain limited. The discovery of new drugs to treat these diseases has been slow for decades. An occasional favorable outcome, trastuzumab, in patients with HER2 protein-overexpressing tumors, is welcome but not sufficient. For advanced gastroesophageal adenocarcinoma (AGC), fluoropyrimidines (given orally or intravenously) plus a platinum compound (usually cisplatin) have been accepted as a global reference to streamline new drug development. The addition of a third cytotoxic (docetaxel or epirubicin) can produce modest prolongation of overall survival. In some European countries, the irinotecanbased regimen is considered as an alternative to platinum-based first-line therapy. Selecting a safe, effective, and convenient regimen is desirable and is the focus of current research. Additionally, it appears that survival differences by regions (e.g., Asians survive longer compared to Western and South American patients) are likely due to second- and third-line therapies, differences in tumor biology, or unknown reasons. Future progress could come from 1 of 2 approaches: (1) conducting many empiric phase III trials in unselected patients or (2) through detailed studies of molecular biology to develop rational therapies. We provide a brief update on the treatment of AGC.