Combination chemotherapy has been shown to be superior to single-agent therapy in gastric and gastroesophageal cancers. However, there is no consensus regarding the optimal regimen. Epirubicin-containing regimens are considered standard in parts of Europe, but the role of anthracyclines remains debatable. In this Viewpoint, we question the continued use of anthracyclines in the treatment of gastroesophageal cancers and discuss why we feel that it is time to move on.
Anthracyclines are associated with serious toxic effects including alopecia, myelosuppression, febrile neutropenia, stomatitis, arrhythmias, and congestive heart failure. These toxic effects must be carefully weighed against expected treatment benefits. Although epirubicin-containing regimens have shown improvement in survival for both resectable and advanced gastroesophageal cancers, the exact contribution of epirubicin has never been demonstrated in a head-to-head comparison with a comparable nonanthracycline-containing arm in any phase III randomized trial. Evidence supporting anthracycline use is mostly derived from small uncontrolled phase II studies, comparisons against no chemotherapy,1 trials comparing widely dissimilar regimens where the exact contribution of the anthracycline cannot be established,2 or a meta-analysis with its own limitations.3