S-1-Based Chemoradiotherapy Followed by Consolidation Chemotherapy With S-1 in Elderly Patients With Esophageal Squamous Cell Carcinoma: A Multicenter Phase II Trial.

Introduction: Intensive treatments can often not be administered to elderly patients with esophageal squamous cell carcinoma (ESCC), leading to a poorer prognosis. This multi-center phase II trial aimed to determine the toxicity profile and efficiency of S-1-based simultaneous integrated boost radiotherapy (SIB-RT) followed by consolidation chemotherapy with S-1 in elderly ESCC patients and to evaluate the usefulness of comprehensive geriatric assessment (CGA). Patients and Methods: We prospectively enrolled 46 elderly patients (age ≥ 70 years) with histopathologically proven ESCC. The patients underwent pretreatment CGA followed by SIB-RT (dose, 59.92 Gy/50.4 Gy) in 28 daily fractions administered using intensity-modulated radiotherapy or volumetric-modulated arc therapy. S-1 was orally administered (40-60 mg/m2) concurrently with radiotherapy and 4-8 weeks later, for up to four 3-week cycles at the same dose. Results: The median survival time was 22.6 months. The 1- and 2-year overall survival rates were 80.4 and 47.8%, respectively. The overall response rate was 78.3% (36/46). The incidence of grade 3-4 toxicities was 28% (13/46). The most common grade 3-4 toxicities were radiation esophagitis (5/46, 10.9%), nausea (4/46, 8.7%), anorexia (3/46, 6.5%), and radiation pneumonitis (3/46, 6.5%). There were no grade 5 toxicities. CGA identified that 48.8% of patients were at risk for depression and 65.5% had malnutrition. Conclusion: Concurrent S-1 treatment with SIB-RT followed by 4 cycles of S-1 monotherapy yielded satisfactory tumor response rates and manageable toxicities in selected elderly patients with ESCC. Pretreatment CGA uncovered numerous health problems and allowed the provision of appropriate supportive care. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT02979691.