Neoadjuvant therapy of esophageal cancer

Neoadjuvant (preoperative) chemotherapy, with or without radiotherapy, is under intense study. There are theoretical and practical reasons for the preoperative use of systemic therapy: (a) laboratory studies support the use of preoperative treatment in animal models, (b) the relapse pattern of esophageal cancer is primarily systemic and (c) the impact on palliation if response is associated with an improved resection rate. Three techniques involving systemic therapy are currently under investigation: (a) chemotherapy alone followed by a planned surgical procedure; (b) chemotherapy and concurrent radiotherapy followed by a planned surgical procedure; (c) chemotherapy and radiotherapy without surgery. Phase II trials of the first technique have demonstrated its feasibility without an increase in operative morbidity or mortality. Two small-scale phase III trials have confirmed chemotherapy's efficacy but have not clearly demonstrated an impact on survival. Large-scale phase III trials are under way, or about to begin, to test definitively the hypothesis that neoadjuvant chemotherapy improves disease-free and overall survival in operable patients. The second technique has also been tested in small-scale phase II trials. Most recently, a large-scale phase II trial has been reported which suggests that this technique has not had a major effect on resection rates or on long-term survival for most patients. These treatment plans are tolerable if careful attention to detail is given. Definitive phase III trials testing the superiority of multimodality treatments over radiotherapy alone or surgery alone are under way.