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

Nature Clinical Practice Oncology volume 4, pages 282–294 (2007)Cite this article

Abstract

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.

Key Points

  • Combined chemotherapy and radiotherapy yields enhanced tumor cell kill

  • The molecular mechanisms for this synergy are incompletely understood

  • Translation of the effect of chemoradiotherapy to clinical benefit has been demonstrated by multiple clinical trials

  • Efforts to intensify therapy using currently available agents have been unsuccessful and/or have resulted in unacceptable degrees of toxicity

  • Future studies will incorporate biologic, targeted therapies, with the goal of further improving survival

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Figure 1: Approaches that use systemic agents to enhance the effects of radiation

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Authors and Affiliations

  1. L Kleinberg is Associate Professor of Oncology at the Department of Radiation Oncology and Radiation Molecular Sciences, and MK Gibson is Assistant Professor of Oncology and AA Forastiere is Professor of Oncology, all at the Upper Aerodigestive Group at The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins, Baltimore, MD, USA.,

    Lawrence Kleinberg, Michael K Gibson & Arlene A Forastiere

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Correspondence to Arlene A Forastiere.

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Kleinberg, L., Gibson, M. & Forastiere, A. Chemoradiotherapy for localized esophageal cancer: regimen selection and molecular mechanisms of radiosensitization. Nat Rev Clin Oncol 4, 282–294 (2007). https://doi.org/10.1038/ncponc0796

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