Esophageal cancer, undoubtedly one of the most deadly malignancies encountered in the United States, is associated with a 5-year survival rate of only about 5%. While good results have been obtained with multimodal therapy (chemotherapy and radiation therapy), some retrospective studies have shown improved survival with endoscopic Nd:YAG laser therapy. To date, no prospective study has been performed to evaluate the merits of endoscopic laser therapy, or its mechanism of action. Objectives: To determine 1) if early (neoadjuvant) treatment with endoscopic laser therapy can improve overall survival; 2) if improvement in survival is due to laser induced improvement of swallowing function, resulting in improved nutrition; 3) if laser therapy improves the quality of life; 4) if early recanalizing of the lumen and debulking of the tumor by the laser reduces the toxicity from chemotherapy (CTX) and radiation therapy (XRT); and 5) if staging by endoscopic ultrasound predicts outcome. Patient Eligibility: 1) All patients with squamous cell cancer or adenocarcinoma of the esophagus, who have not been previously treated with XRT, CTX, or laser therapy; and 2) Patients with a recurrence after surgery. Treatment Plan: Patients will be evaluated in a combined clinic, including a surgeon, gastroenterologist, oncologist, radiation oncologist, and registered dietician. Pre-entry evaluation will include CT scan, UGI series, esophageal transit scintigraphy, endoscopic ultrasound, nutritional assessment, calorie and nutrient intake diary, indirect calorimetry, and Karnofsky performance assessment. Patients determined to be curable by surgery will be excluded. Eligible patients will be randomized to receive either 1) endoscopic Nd-YAG laser therapy followed by CTX and XRT, or 2) just CTX and XRT. Endoscopic laser therapy will be performed to debulk non- obstructing lesions, or to provide a lumenal diameter of at least 11 mm. Energy will be applied in 0.5 sec pulses of 50-100 watts each. Sessions will be repeated every other day until a satisfactory result has been obtained. At the conclusion of the laser therapy, CTX and XRT will commence. CTX will consist of 4 cycles of 5-Fluorouracil (1 gm/m2/day administered continuously for 4 days) and cisplatin (75 mg/m2 on day 1,2,3 and 4). XRT will consist of daily administration of radiation starting on the first day of CTX, and concluding after the administration of 6,000-7,000 cGy. Response Assessment:Response will be measured using CT scanning, UGI series, endoscopic ultrasound, endoscopy, dietary profiles, esophageal transit scans, nutritional assessments, and patient interviews. Statistics: Based on a 20% 1-year survival, a desired 25% improvement, power=0.80, significance less than 0.05, and """"""""off study"""""""" rate of 15%, the study should require 120 patients. Data from our Tumor Registry indicates that accrual should take 2.7 yrs. Records will be analyzed with SAS on an IBM mainframe computer. At 18 mos. data will be evaluated for stopping criteria, Data will be analyzed by intent-to- treat groupings, (both groups will be offered laser therapy for late palliation). Outcome Parameters: overall and disease-free survival, response rate, time to response, incidence and type of toxicity, dysphagia score, esophageal transit rate, change in lumenal diameter, tumor size, functional status, nutritional status, and nutrient intake.
