Chemoradiotherapy for localized esophageal cancer: regimen selection and molecular mechanisms of radiosensitization

Concurrent chemoradiotherapy administered either before surgery or as definitive treatment has a central role in the multimodality treatment of locally advanced esophageal cancer. Initial studies of this combined-modality regimen were based on models of squamous-cell cancers from other primary sites; this approach progressed from use of bleomycin or fluorouracil plus cisplatin concurrent with radiation in early trials, to the integration of taxanes, camptothecins and platinum analogs in recent trials. These trials demonstrated the tumoricidal effect of concurrent chemotherapy and radiotherapy and showed the survival advantages of this approach. Preoperative concurrent chemoradiation is used to downstage the tumor, ideally to a pathological complete response status in which there is no residual tumor in the resected primary and nodal tissues. A pathological complete response is associated with long-term survival but occurs in a minority (30%) of patients. While clinical trials have demonstrated an improvement in survival with concurrent chemoradiotherapy this effect is limited, as indicated by the plateau in survival beyond 5 years of approximately 30% or less. The recent clinical development of biologic, targeted therapies provides a new avenue for the study of chemoradiotherapy and an opportunity to increase long-term survival.