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.

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 III colon cancer.

PATIENTS AND METHODS:

After curative resection, patients were randomly assigned to receive XELOX, as oxaliplatin 130 mg/m(2) on day 1 and capecitabine 1,000 mg/m(2) 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), and OS HR was 2.75 (95% CI, 1.65 to 4.59; 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.

• Authors: Hans-Joachim Schmoll, Josep Tabernero, Jean Maroun, Filippo de Braud, Timothy Price, Eric Van Cutsem, Mark Hill, Silke Hoersch, Karen Rittweger, Daniel G Haller
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 33 Issue 32 Pg. 3733-40 (Nov 10 2015) ISSN: 1527-7755 [Electronic] United States
• PMID: 26324362 (Publication Type: Clinical Trial, Phase III, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial)
• Copyright: © 2015 by American Society of Clinical Oncology.

Chemical References

• Organoplatinum Compounds
• Oxaloacetates
• Oxaliplatin
• Deoxycytidine
• Capecitabine
• Leucovorin
• Fluorouracil

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, therapeutic use)
• Capecitabine (administration & dosage)
• Chemotherapy, Adjuvant
• Colonic Neoplasms (drug therapy, mortality, pathology)
• Deoxycytidine (administration & dosage, analogs & derivatives)
• Disease-Free Survival
• Drug Administration Schedule
• Female
• Fluorouracil (administration & dosage, analogs & derivatives)
• Humans
• Kaplan-Meier Estimate
• Leucovorin (administration & dosage)
• Male
• Middle Aged
• Neoplasm Staging
• Organoplatinum Compounds (administration & dosage)
• Oxaliplatin
• Oxaloacetates
• Proportional Hazards Models
• Treatment Outcome