Chemoradiation in the management of esophageal cancer

The combination of chemotherapy, fluorouracil and cisplatin, and radiation has improved outcome for patients with esophageal cancer. A randomized controlled trial confirmed a long-term survival benefit when this chemotherapy was added to radiotherapy for squamous cell carcinoma, but the approach has not been definitively assessed in patients with adenocarcinoma. Preoperative chemoradiotherapy has been tested in numerous phase II studies and underpowered or flawed phase III studies. Nevertheless, collectively, the evidence strongly suggests that preoperative chemoradiotherapy improves outcome, and thus, this strategy has become a standard treatment option. Attempts to improve outcome by intensifying conventional cytotoxic drugs or increasing the radiation dose have not been successful. Camptothecin and taxane-based regimens combined with radiation have altered the toxicity profile, but substantial improvement in survival outcomes has yet to be demonstrated. Future improvements will likely require the incorporation of targeted agents that add minimally to existing toxicity, the use of molecular predictors of response to individualize selection of the chemotherapeutic regimen, and early identification of responders such that therapy might be altered dynamically.