Michael K. Gibson, MD, PhD

Esophageal adenocarcinoma (EAC) affects approximately 11,000 persons per year in the United States, is increasing in incidence, and is associated with an exceptionally high mortality rate.[1-4] In this issue of ONCOLOGY, Krasna reviews the role of multimodality therapy in the treatment of EAC. Poor outcome in patients with EAC is reflective of both deficiencies in early detection and the inadequacy of available therapies across stages.

Based on positive results from the Radiation Therapy Oncology Group (RTOG) 85-01 trial, the conventional nonsurgical treatment of esophageal carcinoma is combined-modality therapy. Dose intensification of the RTOG 85-01 regimen, examined in the Intergroup (INT)-0123/RTOG 94-05 trial, did not improve local control or survival. Areas of clinical investigation include the development of combined-modality therapy regimens with newer systemic agents, the use of 18F-fluorodeoxyglucose positron-emission tomography to assist in the development of innovative radiation treatment planning techniques, and the identification of prognostic molecular markers. The addition of surgery following primary combined-modality therapy apparently does not improve survival, but this finding is controversial.

The epidermal growth factor receptor (EGFR) promotes the growth of different cell types and has been implicated in tumorigenesis. The EGFR comprises a family of four structurally similar tyrosine kinases with a complex link to downstream signaling molecules that ultimately regulate key cell processes. Anti-EGFR agents have been developed as promising therapeutic anticancer targets, and some have been recently approved for the treatment of non-small-cell lung cancer and colon cancer. The two anti-EGFR therapies with the greatest clinical application are monoclonal antibodies that block the binding of ligands to EGFR and small-molecule tyrosine kinase inhibitors that inhibit the binding of adenosine triphosphate to the internal tyrosine kinase receptor of EGFR. We attempt to give an overview of the EGFR function and biology, focusing on the most important clinical findings and applications of EGFR inhibitors in lung and head and neck cancer.

Argiris and colleagues presenta comprehensive review of25 years of phase II/III trialsusing multimodality therapy for locallyadvanced head and neck squamouscell cancer (HNSCC). Theyfocus on two approaches: inductionchemotherapy followed by definitivelocal therapy (surgery and/or radiotherapy)and concurrent chemoradiotherapy.In sorting through thesetrials, the authors review the controversiesin the management of locallyadvanced HNSCC, while also presentinga rationale for a unified approach-combining induction andconcomitant chemoradiotherapy in amultimodality treatment paradigm.Evidence from several recent studiessuggests that this strategy will benefita subset of patients with locally advanceddisease. The stage is set forthe reevaluation of the benefit of inductionchemotherapy prior to definitivechemoradiation. To that end, threedifferent prospective phase III trialsare under way in the United States.