New developments in the treatment of esophageal cancer

Esophageal cancer is a rare but highly virulent malignancy occurring in the United States and other Western countries. Adenocarcinoma of the esophagus has had the most rapid rate of increase of any solid tumor malignancy in the United States. Controversy continues about the optimal surgical approach for the treatment of locally advanced esophageal cancer. Combined chemoradiotherapy is the standard of care in the nonsurgical management of esophageal cancer. Trials of preoperative chemotherapy followed by surgery have not shown a consistent benefit for the addition of chemotherapy to surgery. Preoperative chemoradiotherapy followed by surgery continues to be actively studied in the surgical management of locally advanced esophageal cancer. Pathologic complete responses are seen in 20-40% of patients, with 5-year survival achieved in 30-35% of patients. Recent randomized trials evaluating the role of surgery after completion of chemoradiotherapy have not clearly shown a benefit for the routine use of surgery after chemoradiotherapy. The toxicity of conventional fluorouracil, cisplatin, and radiation have led researchers to evaluate newer agents, such as the taxanes and irinotecan, in combined chemoradiotherapy trials. These trials have indicated promising antitumor activity and therapy tolerance, depending on the dose and schedule of therapy administered. Increasing the dose of radiotherapy or adding a brachytherapy boost to chemoradiotherapy has not improved the outcome of treatment in clinical trials. The advent of newer, targeted therapies, including agents directed against growth factor receptor pathways, tumor angiogenesis, and tumor invasion and metastasis, is leading to a new generation of clinical trials combining these agents with conventional cytotoxic chemotherapy and radiation.