Capecitabine plus oxaliplatin (XELOX) versus 5-fluorouracil/folinic acid plus oxaliplatin (FOLFOX-4) as second-line therapy in metastatic colorectal cancer: a randomized phase III noninferiority study.

Abstract

BACKGROUND:

To demonstrate the noninferiority of capecitabine plus oxaliplatin (XELOX) versus 5-fluorouracil/folinic acid and oxaliplatin (FOLFOX-4) as second-line therapy in patients with metastatic colorectal cancer after prior irinotecan-based chemotherapy.

PATIENTS AND METHODS:

A total of 627 patients were randomly assigned to receive XELOX (n = 313) or FOLFOX-4 (n = 314) following disease progression/recurrence or intolerance to irinotecan-based chemotherapy. The primary end point was progression-free survival (PFS).

RESULTS:

PFS for XELOX was noninferior to FOLFOX-4 [hazard ratio (HR) = 0.97; 95% confidence interval (CI) 0.83-1.14] in the intention-to-treat (ITT) population. Median PFS was 4.7 months with XELOX versus 4.8 months with FOLFOX-4. The robustness of the primary analysis was supported by multivariate and subgroup analyses. Median overall survival in the ITT population was 11.9 months with XELOX versus 12.5 months with FOLFOX-4 (HR = 1.02; 95% CI 0.86-1.21). Treatment-related grade 3/4 adverse events occurred in 50% of XELOX- and 65% of FOLFOX-4-treated patients. Whereas grade 3/4 neutropenia (35% versus 5% with XELOX) and febrile neutropenia (4% versus < 1%) were more common with FOLFOX-4, grade 3/4 diarrhea (19% versus 5% with FOLFOX-4) and grade 3 hand-foot syndrome (4% versus < 1%) were more common with XELOX.

CONCLUSION:

XELOX is noninferior to FOLFOX-4 when administered as second-line treatment in patients with metastatic colorectal cancer.

• Authors: M L Rothenberg, J V Cox, C Butts, M Navarro, Y-J Bang, R Goel, S Gollins, L L Siu, S Laguerre, D Cunningham
• Journal: Annals of oncology : official journal of the European Society for Medical Oncology (Ann Oncol) Vol. 19 Issue 10 Pg. 1720-6 (Oct 2008) ISSN: 1569-8041 [Electronic] England
• PMID: 18550577 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Organoplatinum Compounds
• Oxaliplatin
• Deoxycytidine
• Capecitabine
• Irinotecan
• Leucovorin
• Fluorouracil
• Camptothecin

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Camptothecin (analogs & derivatives, pharmacology)
• Capecitabine
• Colorectal Neoplasms (drug therapy, pathology)
• Deoxycytidine (administration & dosage, adverse effects, analogs & derivatives)
• Disease Progression
• Drug Resistance, Neoplasm
• Female
• Fluorouracil (administration & dosage, adverse effects, analogs & derivatives)
• Humans
• Irinotecan
• Leucovorin (administration & dosage, adverse effects)
• Male
• Middle Aged
• Neoplasm Metastasis
• Organoplatinum Compounds (administration & dosage, adverse effects)
• Oxaliplatin