A concurrent chemoradiotherapy (CCRT) regimen was about as safe as — and more effective than — radiotherapy (RT) alone in older patients with advanced esophageal cancer, according to a study published in JAMA Oncology.

The study authors noted that CCRT with fluorouracil and cisplatin is the standard treatment for inoperable, locally advanced esophageal cancer in patients with good performance status, but many older patients cannot tolerate this treatment.

The fluoropyrimidine S-1 “is designed to have enhanced anticancer activity and reduced toxicity,” according to the authors, so they tested a CCRT regimen incorporating S-1 in a phase 3 trial (ClinicalTrials.gov Identifier: NCT02813967).

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The trial enrolled 298 patients with stage IB to IVB esophageal cancer. At baseline, the patients’ median age was 77 years (range, 74-80 years), and 60.4% were men. About half of patients (50.7%) had stage III or IV disease, and nearly all patients (99.3%) had squamous cell carcinoma.

The patients were randomly assigned to receive CCRT (n=149) or RT alone (n=149). Patients in the CCRT arm received RT at 54 Gy in 30 fractions (1.8 Gy/day, 5 days a week) with concurrent S-1 (70 mg/m2 per day on days 1 to 14 and 29 to 42). Patients in the RT arm received 60 Gy in 30 fractions (2.0 Gy/day, 5 days a week).

The complete response rate was significantly higher with CCRT than with RT alone — 41.6% and 26.8%, respectively (P =.007). The rate of locoregional progression was significantly lower with CCRT than with RT alone — 28.2% and 40.9%, respectively (P =.02).

Progression-free survival (PFS) and overall survival (OS) outcomes were significantly better with CCRT. The median PFS was 18.7 months with CCRT and 9.5 months with RT (hazard ratio [HR], 0.66; 95% CI, 0.50-0.87; P =.003).

The median OS was 24.9 months in the CCRT arm and 15.4 months in the RT arm (HR, 0.63; 95% CI, 0.47-0.85; P =.002). The 2-year OS rate was 53.2% and 35.8%, respectively, and the 3-year OS rate was 43.4% and 28.4%, respectively.

The rate of grade 3-5 adverse events was generally similar between the arms. The exception was leukopenia, which occurred more frequently in the CCRT arm than in the RT arm (9.5% vs 2.7%; P =.01).

Treatment-related deaths occurred in 2.0% of patients in the CCRT arm and 2.7% of those in the RT arm.

“CCRT with S-1 was tolerable and provided significant benefits over RT alone in older patients with esophageal cancer,” the study authors concluded.


Ji Y, Du X, Zhu W, et al. Efficacy of concurrent chemoradiotherapy with S-1 vs radiotherapy alone for older patients with esophageal cancer: A multicenter randomized phase 3 clinical trial. JAMA Oncol. Published Aug. 5, 2021. doi: 10.1001/jamaoncol.2021.2705