Concurrent Chemoradiotherapy Tolerable, More Effective Than Radiotherapy Alone Among Older Adults With Esophageal Cancer

Investigators assessed the safety and efficacy of concurrent chemoradiotherapy with S-1 vs radiotherapy alone in older adults with esophageal cancer.

For older patients with esophageal cancer, a phase 3 randomized, open-label clinical trial found concurrent chemoradiotherapy (CCRT) with S-1 (tegafur, 5-chloro-2,4-dihydroxypyridine, and potassium oxonate) was tolerable and more effective compared with radiotherapy (RT) alone. These findings were published in JAMA Oncology.

Patients (N=298) aged 70 to 85 years who had stage IB-IVB esophageal cancer were recruited at 23 centers in China between 2016 and 2018. Patients were assigned in a 1:1 ratio to receive CCRT with 70 mg/m2/day S-1 (n=149) or RT (n=149). Safety and efficacy were evaluated up to 3 years.

The CCRT and RT cohorts included individuals aged median 77 (IQR, 74-79) and 77 (IQR, 74-80) years, 59.7% and 61.1% were men, 53.7% and 55.7% had a middle thoracic tumor, 31.5% and 30.9% had an upper thoracic tumor, 60.4% and 59.1% had a tumor ³5 cm in length, 47.7% and 41.6% were stage III, and 32.2% and 41.6% were stage IIA, respectively. Randomized treatment was completed by 77.2% of the CCRT cohort and 89.9% of the RT group.

A total of 54.4% of the CCRT and 70.5% of the RT cohorts died, indicating a more favorable overall survival among the CCRT group (hazard ratio [HR], 0.63; 95% CI, 0.47-0.85; P =.002). Survival rates at 1 year were 74.3% and 59.7%, 53.2% and 35.8% at 2 years, and 43.4% and 28.4% at 3 years among the CCRT and RT cohorts, respectively. These rates corresponded with a median overall survival of 24.9 months for CCRT and 15.4 months for RT.

Stratified by differing characteristics, the overall survival was increased among CCRT recipients among all subgroups. The clinical complete response rate was higher for the CCRT group (41.6% vs 26.8%; P =.007).

Disease progression occurred during the final follow-up among 53.7% of the CCRT and 65.8% of the RT (P =.03) cohorts. Fewer recipients of CCRT had locoregional progression (28.2% vs 40.9%; P =.02).

CCRT was associated with increased adverse events of neutropenia (33.8% vs 22.1%; P =.04), thrombocytopenia (25.7% vs 12.8%; P =.007), constipation (15.5% vs 7.4%; P =.04), and leukopenia (9.5% vs 2.7%; P =.01). Treatment-related deaths occurred among 3 patients in the CCRT and 4 patients in the RT treatment arms.

This study was limited by not including quality of life or functional status measures.

The study authors concluded that CCRT with S-1 was tolerable and had favorable efficacy outcomes compared with RT alone among older adults with advanced esophageal cancer.


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. 2021;7(10):1459-1466. doi:10.1001/jamaoncol.2021.2705