A phase I dose escalation study of S-1 with concurrent radiotherapy in elderly patients with esophageal cancer.

ABSTRACT

BACKGROUND: Concurrent chemoradiotherapy (CRT) with 5-fluorouracil (5-FU) and cisplatin (CDDP) are often associated with significant incidence of toxic effects in elderly patients with esophageal cancer. This phase I trial was designed to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of S-1, an oral 5-FU derivative, when given with radiotherapy in elderly patients. METHODS: Patients who were age of 70 years or older with histologically confirmed esophageal cancer, and had an Eastern Cooperative Oncology Group (ECOG) score of 0-2 were eligible for this study. Radiotherapy was administered in 1.8 Gy fractions 5 times weekly to a total dose of 54 Gy. S-1 was administered on days 1-14 and 29-42 at the following dosages 60, 70, and 80 mg/m(2)/day. TRIAL REGISTRATION NCT01175447 (ClinicalTrials.gov). RESULTS: Twelve previously untreated patients were enrolled in this study. No grade 3 or 4 toxicity was observed in six patients treated at the 60 and 70 mg/m(2) dose levels. DLT was observed in four of six patients treated at the 80 mg/m(2) dose level. Two patients developed grade 3 esophagitis, one patient developed grade 3 esophagitis and pneumonitis, and one patient developed grade 3 thrombocytopaenia. Endoscopic complete response (CR) was observed in eight patients (66.7%). The median progression free survival (PFS) was 20 months and median overall survival was 29 months. CONCLUSIONS: The MTD of S-1 was 80 mg/m(2), and the recommended dose (RD) for phase II studies was 70 mg/m(2). This regimen was well tolerated and active in elderly patients with esophageal cancer, meriting further investigation in phase II studies.