Capecitabine plus oxaliplatin compared with fluorouracil/folinic acid as adjuvant therapy for stage III colon cancer: Final Results of the NO16968 randomized controlled phase III trial

Hans Joachim Schmoll, Josep Tabernero, Jean Maroun, Filippo De Braud, Timothy Price, Eric Van Cutsem, Mark Hill, Silke Hoersch, Karen Rittweger, Daniel G. Haller

Research output: Contribution to journalArticle

Abstract

Purpose: To report the final efficacy findings and biomarker analysis from the NO16968 trial comparing bolus fluorouracil/folinic acid (FU/FA) with capecitabine plus oxaliplatin (XELOX) in resected stage II colon cancer. Patients and Methods: After curative resection, patients were randomly assigned to receive XELOX, as oxaliplatin 130 mg/m2 on day 1 and capecitabine 1,000 mg/m2 twice daily on days 1 to 14 every 3 weeks, or bolus FU/FA, as the Mayo Clinic or Roswell Park regimens, for 6 months. The primary end point was disease-free survival (DFS). Secondary end points included overall survival (OS) Results: The intention-to-treat population comprised 1,886 patients (XELOX, n = 944; FU/FA, n = 942) Seven-year DFS rates were 63% and 56% in the XELOX and FU/FA groups, respectively (hazard ratio [HR], 0.80; 95% CI, 0.69 to 0.93; P =.004). Seven-year OS rates were 73% and 67% in the XELOX and FU/FA groups, respectively (HR, 0.83; 95% CI, 0.70 to 0.99; P =.04) A total of 68% and 77% of patients who experienced relapse or a new colorectal cancer in the XELOX and FU/FA groups, respectively, received drug treatment for metastatic disease. Four hundred ninety-eight patients consented to the biomarker analysis: 242 in the XELOX group and 256 in the FU/FA group. Low tumor expression of dihydropyrimidine dehydrogenase may be predictive for XELOX efficacy; in the XELOX group, for high versus low dihydropyrimidine dehydrogenase expression levels, DFS HR was 2.45 (95% CI, 1.55 to 3.86; P .001). In the FU/FA group, no statistically significant associations were observed between any tumor biomarker and outcomes Conclusion: XELOX improved OS compared with bolus FU/FA in patients with resected stage III colon cancer after a median follow-up of almost 7 years. XELOX should be considered a standard adjuvant treatment option in patients with stage III disease. Tumoral dihydropyrimidine dehydrogenase expression is a promising predictive, and potentially, highly clinically relevant, biomarker for XELOX efficacy requiring further prospective evaluation.

Original languageEnglish
Pages (from-to)3733-3740
Number of pages8
JournalJournal of Clinical Oncology
Volume33
Issue number32
DOIs
Publication statusPublished - Nov 10 2015

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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