Single-institute Phase I/II Trial of Alternating Chemoradiotherapy with 5-FU and Nedaplatin for Esophageal Carcinoma

Abstract

Aim: To assess the efficacy and feasibility of alternating chemoradiotherapy for esophageal cancer. Materials and Methods: Patients, with previously untreated esophageal cancer, Eastern Cooperative Oncology Group performance status of 0 to 2, age 20 to 75 years and sufficient organ function, were eligible for this study. Three cycles of systemic chemotherapy with the continuous infusion of 3500 mg/m² of 5-fluorouracil (5-FU: days 1-5) and a 6-h infusion of nedaplatin (NDP; day 6: 120-140 mg/m²), were accompanied by thoracic irradiation of 63 Gy in 35 fractions over 7 weeks. Radiation therapy was stopped during systemic chemotherapy (alternating setting). In the phase I part, the dose of nedaplatin was increased to define dose-limiting toxicities. For the phase II part, patients with distant metastasis were excluded. Results: From 1998 through 2002, 40 patients were recruited for this protocol study. The median patient age was 54 years (range, 49-65 years) for the phase I and 58 years (range, 44-73 years) for the phase II trials. There were 35 men and 5 women in this study. For the phase I part (n=15), the maximal tolerated dose of NDP was 140 mg/m²; thus, the recommended dose was 130 mg/m². Twenty-five patients were treated with the recommended doses in the phase II part of the study. Ten patients had T4 disease and 14 patients had stage IV disease in the phase II part of the study. The overall survival rates at 1 and 2 years were 58.9% and 45.9%, respectively. The most frequent toxicities were leukopenia (grade 3 or greater: 80%), followed by thrombocytopenia (56%), granulocytopenia (56%) and anemia (28%). Radiation esophagitis of grade 3 or greater developed in 6 patients (24%). Two patients died of radiation pneumonitis. The actual dose intensities of NDP and 5-FU were 68.8% and 73.3%, respectively. Conclusion: This intensive treatment for esophageal cancer was feasible and effective; however, moderate-to-severe toxicity occurred. This protocol warrants further clinical evaluation in a multi-institutional prospective study.