A phase II trial of accelerated multimodality therapy for locoregionally advanced cancer of the esophagus and gastroesophageal junction - The impact of clinical heterogeneity

Objectives: This is a report of mature results from a phase II trial of an accelerated multimodality treatment program for locoregionally advanced cancer of the esophagus and gastroesophageal junction with a focus on the impact of clinical heterogeneity on outcomes. A split course of pre- and postoperative hyperfractionated radiation therapy and concurrent chemotherapy was used in an effort to limit perioperative mortality. Methods: Eligibility required a diagnosis of esophageal or gastroesophageal junction cancer and an esophageal ultrasound stage of at least T3, N1, or M1A. Patients received a 12-day induction course of radiation (1.5 Gy twice a dose to a dose of 30 Gy) concurrent with 4-day continuous intravenous infusions of cisplatin (20 mg/m(2) per day) and 5-fluorouracil (1000 mg/m(2) per day) beginning on day 1. Surgery followed in 4 to 6 weeks followed 6 to 10 weeks later by a second, identical course of chemoradiotherapy. Results: From October 1999 through March 2003, 93 patients were enrolled; 96% were white, 86% male, and 83% had adenocarcinoma. Resection was possible in 83 patients (89%) with 4 (5%) perioperative deaths. With a median follow up of 50 months (range, 34-72 months), the 3-year projected overall survival rate is 27.9%, freedom from recurrence 30.5%, and distant metastatic control 32.4%. Locoregional control in resected patients is 86%. Freedom from recurrence and distant control were significantly better in patients with 1) earlier pretreatment clinical stage, 2) earlier postinduction pathologic stage, 3) squamous cell cancer, and 4) a pathologic response. Conclusions: This accelerated multimodality treatment program is feasible and perioperative mortality proved acceptable. Despite excellent locoregional control, freedom from recurrence, and overall