Chemotherapeutic and targeted strategies for locally advanced and metastatic esophageal cancer

Introduction: Esophageal cancer represents a major health care problem worldwide and its prevalence is rapidly increasing. A key challenge in the treatment of both locally advanced and metastatic disease is to improve our understanding of the underlying molecular biology. Herein we discuss the most active chemotherapies and targeted agents for esophageal cancer, and explore potential differences in the disease between Eastern and Western countries. Methods: We reviewed the literature for trials involving chemotherapy and targeted agents in locally advanced and metastatic disease in the last 20 years. The search was supplemented by a review of the abstracts presented at the annual American Society of Clinical Oncology meetings from 1992 to 2012. Results: Neoadjuvant chemo-radiation followed by surgery remains standard of care for operable disease. Definitive chemo-radiation can be considered for locally advanced squamous cell tumors. Platinum-based combination chemotherapy is preferable in the first-line metastatic setting. Recently, HER2, EGFR, and VEGF-targeted agents have been extensively investigated as single agents or in combination with chemotherapy. Several new targets are being explored. Conclusions: There have been incremental improvements in our understanding of the molecular biology of esophageal cancer, and ethnic differences between Asian and Western populations are becoming apparent. Next-generation sequencing has failed to demonstrate significant oncogenic drivers; however, the addition of trastuzumab to chemotherapy for HER2-amplified tumors has been validated in the metastatic setting and is undergoing investigation in operable disease. Epigenetic therapeutics may provide additional benefit in future years for this difficult-to-treat disease.