In a Chinese phase III trial (CRTCOESC) reported in the Journal of Clinical Oncology, Jia et al found that neither capecitabine nor XELOX (capecitabine, oxaliplatin) improved 2-year overall survival vs cisplatin/fluorouracil as part of definitive concurrent chemoradiotherapy in patients with inoperable locally advanced esophageal squamous cell carcinoma. However, capecitabine was associated with a lower incidence of grade ≥ 3 adverse events than cisplatin/fluorouracil.
Study Details
In the multicenter trial, 246 patients were randomly assigned 1:1:1 between October 2014 and April 2020 to receive one of the following regimens:
- Capecitabine at 625 mg/m2 twice daily on days 1 to 5, 8 to 12, and 15 to 19 every 3 weeks for two cycles (n = 80)
- XELOX as oxaliplatin at 65 mg/m2 once daily on days 1 and 8 and capecitabine (as above) every 3 weeks for two cycles (n = 85)
- Cisplatin/fluorouracil as cisplatin at 75 mg/m2 once daily on day 1 and fluorouracil at 750 mg/m2 once daily on days 1 to 4 every 4 weeks for two cycles (n = 81).
All patients received concurrent intensity-modulated radiation therapy at 50 Gy in 25 fractions. Patients in each treatment group were further randomly assigned to receive either two cycles of consolidation chemotherapy with the same regimen or no consolidation. The primary endpoints were 2-year overall survival and incidence of grade ≥ 3 adverse events.
Key Findings
Overall survival at 2 years was 75% in the capecitabine group (hazard ratio [HR] vs cisplatin/fluorouracil = 0.91, 95% confidence interval [CI] = 0.61–1.35, P = .637), 66.7% in the XELOX group (HR vs cisplatin/fluorouracil = 0.86, 95% CI = 0.58–1.27, P = .444), and 70.9% in the cisplatin/fluorouracil group. Median overall survival was 40.9 months (95% CI = 34.4–49.9 months) in the capecitabine group, 41.9 months (95% CI = 28.6–52.1 months) in the XELOX group, and 35.4 months (95% CI = 30.4–45.4 months) in the cisplatin/fluorouracil group.
The incidence of grade ≥ 3 adverse events was 28.8% in the capecitabine group (P = .034 vs cisplatin/fluorouracil group; P = .332 vs XELOX group), 36.5% in the XELOX group (P = .270 vs cisplatin/fluorouracil group), and 45.7% in the cisplatin/fluorouracil group.
Median overall survival was 41.9 months (95% CI = 34.6–52.8 months) among all patients receiving consolidation chemotherapy vs 36.9 months (95% CI = 28.5–44 months) among all patients not receiving consolidation chemotherapy (HR = 0.71, 95% CI = 0.52–0.99, P = .0403).
The investigators concluded: “Capecitabine or XELOX did not significantly improve the 2-year overall survival rate over cisplatin/fluorouracil in definitive concurrent chemoradiotherapy for inoperable locally advanced esophageal squamous cell carcinoma. Capecitabine showed a lower incidence of grade ≥ 3 adverse events than cisplatin/fluorouracil did.”
Shegan Gao, MD, PhD, of the First Affiliated Hospital (College of Clinical Medicine) of Henan University of Science and Technology, Luoyang, is the corresponding author of the Journal of Clinical Oncology article.
Disclosure: The study was supported by the Henan Province Medical Science and Technology Research Project, Luoyang City Science and Technology Development Plan, and Jiangsu Hengrui Pharmaceuticals Co, Ltd. For full disclosures of the study authors, visit ascopubs.org.
