Abstract | PURPOSE: 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.
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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)
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Copyright | © 2015 by American Society of Clinical Oncology. |
Chemical References |
- Organoplatinum Compounds
- Oxaloacetates
- Oxaliplatin
- Deoxycytidine
- Capecitabine
- Leucovorin
- Fluorouracil
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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
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