S-1 Chemoradiotherapy for Older Patients With Inoperable Esophageal Squamous Cell Carcinoma

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In a Chinese phase III trial reported in JAMA Network Open, Wang et al found that oral S-1 chemotherapy given with simultaneous integrated boost radiotherapy (SIB-RT) and following SIB-RT improved overall survival in patients aged 70 or older with inoperable esophageal squamous cell carcinoma. 

Study Details

In the multicenter trial, 330 patients were randomly assigned between March 2017 and April 2020 to receive SIB-RT with (n = 184) or without (n = 146) concurrent and consolidated S-1.  The planning gross tumor volume received 59.9 Gy, and the planning target volume received 50.4 Gy of radiotherapy in 28 fractions each.  Concurrent S-1 was given twice daily on radiotherapy days (total daily dosage = 40, 50, or 60 mg/m2 based on body surface area); at 4 to 8 weeks after SIB-RT, consolidated S-1 was given at the same dosage on days 1 to 14 in 3-week cycles for four cycles. The primary endpoint was overall survival in the intention-to-treat population.

Key Findings

Median follow-up for surviving patients was 42.9 months (interquartile range [IQR] = 38.8–47.0 months) in the S-1 group and 44.4 months (IQR = 39.3–49.4 months) in the control group. Median overall survival was 28.1 months (IQR = 19.7–36.6 months) in the S-1 group vs 20.1 months (IQR = 13.8–26.5 months) in the control group (hazard ratio [HR] = 0.73, 95% confidence interval [CI] = 0.56–0.96, P = .02). Rates at 1, 2, and 3 years were 72.2% vs 62.3%, 55.7% vs 43.8%, and 46.2% vs 33.9%, respectively.

Median progression-free survival was 19.5 months (IQR = 12.8–26.2 months) in the S-1 group vs 11.1 months (IQR = 6.7–15.4 months) in the control group (HR = 0.76, 95% CI = 0.58–0.98, P = .04). Rates at 1, 2, and 3 years were 60.8% vs 49.3%, 45.4% vs 37.0%, and 37.3% vs 27.9%, respectively.

No significant difference between groups was observed in terms of the incidence of treatment-related grade ≥ 3 adverse events; the most common grade 3 or 4 events were esophagitis (11.9%), leukopenia (8.5%), and nausea (8.5%) in the S-1 group, and esophagitis (5.6%) and leukopenia (4.5%) in the control group. Adverse events led to death in five patients in the S-1 group (from pneumonitis in three and fever in two) and five patients in the control group (from pneumonitis in three and myelosuppression in two).

The investigators concluded: “These findings suggest that oral S-1 chemotherapy administered with SIB-RT should be considered as an alternative treatment option for patients aged 70 years and older with inoperable esophageal squamous cell carcinoma, since it improved survival outcomes without additional treatment-related toxic effects compared with SIB-RT alone.”

Junqiang Chen, MD, of the Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, and Zefen Xiao, MD, of the Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, are the corresponding authors of the JAMA Network Open article.

Disclosure: The study was supported by the Beijing Hope Run Special Fund of the Cancer Foundation of China. For full disclosures of the study authors, visit

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