Capecitabine or Capecitabine Plus Oxaliplatin Versus Fluorouracil Plus Cisplatin in Definitive Concurrent Chemoradiotherapy for Locally Advanced Esophageal Squamous Cell Carcinoma (CRTCOESC): A Multicenter, Randomized, Open-Label, Phase 3 Trial

J Clin Oncol. 2024 Jul 10;42(20):2436-2445. doi: 10.1200/JCO.23.02009. Epub 2024 May 6.

Abstract

Purpose: This phase 3 trial aimed to compare the efficacy and safety of capecitabine or capecitabine plus oxaliplatin (XELOX) with those of fluorouracil plus cisplatin (PF) in definitive concurrent chemoradiotherapy (DCRT) for inoperable locally advanced esophageal squamous cell carcinoma (ESCC).

Methods: Patients were randomly assigned to receive two cycles of capecitabine, XELOX, or PF along with concurrent intensity-modulated radiation therapy. Patients in each arm were again randomly assigned to receive two cycles of consolidation chemotherapy or not. The primary end points were 2-year overall survival (OS) rate and incidence of grade ≥3 adverse events (AEs).

Results: A total of 246 patients were randomly assigned into the capecitabine (n = 80), XELOX (n = 85), and PF (n = 81) arms. In capecitabine, XELOX, and PF arms, the 2-year OS rate was 75%, 66.7%, and 70.9% (capecitabine v PF: hazard ratio [HR], 0.91 [95% CI, 0.61 to 1.35]; nominal P = .637; XELOX v PF: 0.86 [95% CI, 0.58 to 1.27]; P = .444); the median OS was 40.9 (95% CI, 34.4 to 49.9), 41.9 (95% CI, 28.6 to 52.1), and 35.4 (95% CI, 30.4 to 45.4) months. The incidence of grade ≥3 AEs during the entire treatment was 28.8%, 36.5%, and 45.7%, respectively. Comparing the consolidation chemotherapy with the nonconsolidation chemotherapy groups, the median OS was 41.9 (95% CI, 34.6 to 52.8) versus 36.9 (95% CI, 28.5 to 44) months (HR, 0.71 [95% CI, 0.52 to 0.99]; nominal P = .0403).

Conclusion: Capecitabine or XELOX did not significantly improve the 2-year OS rate over PF in DCRT for inoperable locally advanced ESCC. Capecitabine showed a lower incidence of grade ≥3 AEs than PF did.

Trial registration: ClinicalTrials.gov NCT02025036.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Multicenter Study
  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols* / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Capecitabine* / administration & dosage
  • Capecitabine* / adverse effects
  • Capecitabine* / therapeutic use
  • Chemoradiotherapy* / adverse effects
  • Cisplatin* / administration & dosage
  • Cisplatin* / adverse effects
  • Cisplatin* / therapeutic use
  • Esophageal Neoplasms* / mortality
  • Esophageal Neoplasms* / pathology
  • Esophageal Neoplasms* / therapy
  • Esophageal Squamous Cell Carcinoma* / mortality
  • Esophageal Squamous Cell Carcinoma* / pathology
  • Esophageal Squamous Cell Carcinoma* / therapy
  • Female
  • Fluorouracil* / administration & dosage
  • Fluorouracil* / adverse effects
  • Fluorouracil* / analogs & derivatives
  • Fluorouracil* / therapeutic use
  • Humans
  • Male
  • Middle Aged
  • Oxaliplatin* / administration & dosage
  • Oxaliplatin* / adverse effects
  • Oxaliplatin* / therapeutic use
  • Oxaloacetates

Substances

  • Capecitabine
  • Fluorouracil
  • Cisplatin
  • Oxaliplatin
  • Oxaloacetates

Supplementary concepts

  • XELOX

Associated data

  • ClinicalTrials.gov/NCT02025036