13. Aggressive Multimodality Therapy for Stage III Esophageal Cancer: A Phase I/II Study

Pendelton Alexander, Timothy Lipman, John Harmon, Robert Wadleigh

George Washington University and Washington D.C. VAMC

Washington, D.C.

Stage III advanced locoregional esophageal carcinoma is frequently unresectable and a challenge for multimodality therapy. From 1992 to 1998, 33 of 121 total esophageal cancer patients were designated Stage III (15T3N1, 9T4N0, 9T4N1) and medically fit to enter a combined modality protocol with continuous infusion five-flurouracil (CL5-FU) (100-500 mg/mg2/d), high dose external beam irradiation (60 Gy), and interval esophagectomy. Staging before and after induction therapy included computerized tomography, endoscopy and endoscopic ultrasound. Significant toxicity from induction therapy included death (5/33), mucositis (13/33), hand-foot syndrome (3/33), and pneumonitis (5/33). In addition to the five deaths nine other patients did not proceed to operate because of patient refusal (three), esophagorespiratory fistula (two), new primary or metastasis (three), and progression of co-morbidities (one). Restaging demonstrated partial response in 46 percent (13/28). There was a discrepancy between estimation of clinical complete response (CR), 53 percent (15/28), and pathologic CR noted at the time of operation 32 percent (9/28). Complete resections were possible in 14 to 15 patients explored. Complications in four patients included death (one), airway injury (one), urosepsis (one), ascaris infection (one), chylothorax (one) and anastomotic leak (one). Actuarial survival analysis using the Kaplan Meier method and logrank testing showed a median survival time of 14.4 months for the group as a whole, non-resected patients 6.4 months vs. Resected patients 28.5 months (p=0.04), T4N0 27.1 months vs. T3N1 + T4N1 8.2 months (p=0.02), and PR 9.7 months vs. Clinical CR 29 months (p=0.005). Treatment failure is predominately distant metastases with good local control in resected patients. In spite of significant toxicity, C15FU, high dose irradiation, and resection can be helpful in Stage III esophageal cancer. Even in bulky advance locoregional disease, nodal status is an important determinant of survival.