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/m2 per day) and 5-fluorouracil (1000 mg/m2 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 survival proved disappointing reflecting the frequency of distant metastases. Heterogeneity in patient populations makes comparisons with similar nonrandomized experiences problematic.