No Survival Difference for Adjuvant Capecitabine vs 5-FU With or Without Oxaliplatin in Stage III Colon Cancer


Key Points

  • Outcomes did not differ for capecitabine vs fluorouracil/leucovorin regimens.
  • The addition of oxaliplatin did not worsen postrelapse survival.

In an analysis reported in The Lancet Oncology, Schmoll et al found no difference in survival outcomes with adjuvant capecitabine vs fluorouracil (5-FU)/leucovorin with or without oxaliplatin in patients with stage III colon cancer and no adverse impact of adjuvant oxaliplatin on post-relapse survival.

Study Details

The study was a pooled analysis of outcomes in 8,734 patients from four randomized trials (NSABP C-08, XELOXA, X-ACT, and AVANT). The treatment regimens included XELOX (oxaliplatin and capecitabine); leucovorin and 5-FU; capecitabine; FOLFOX-4 (leucovorin, 5-FU, and oxaliplatin); and modified FOLFOX-6 (mFOLFOX-6). Disease-free survival was the primary endpoint in all trials. Multiple Cox proportional hazards regression analyses adjusted for sex, age, T stage, and N stage.

No Differences by Fluoropyrimidine

No significant differences between the capecitabine with or without oxaliplatin group vs 5-FU/leucovorin with or without oxaliplatin group were found for disease-free survival (adjusted hazard ratio [HR] = 1.02, P = .72; unadjusted HR = 1.01, P = .86]), relapse-free survival (adjusted HR = 1.02, P = .72; unadjusted HR = 1.01, P = .86), or overall survival (adjusted HR = 1.04, P = .50; unadjusted HR = 1.02, P = .65).

There was a significant interaction in overall survival between oxaliplatin and fluoropyrimidine in multiple Cox regression analysis (P = .014), and estimated hazard ratios in the same analysis were 0.75 (95% confidence interval [CI] = 0.63–0.88) for oxaliplatin plus capecitabine and 0.56 (95% CI = 0.48–0.65) for oxaliplatin plus 5-FU/leucovorin. However, there was no significant difference in overall survival in direct comparison of XELOX vs FOLFOX with adjustment for bevacizumab (Avastin) use (HR = 1.12, P = .11), nor were there differences in disease-free survival (HR = 1.00, P = .98) or relapse-free survival (HR = 0.99, P = .85).

Postrelapse Survival

There was no significant difference in postrelapse survival between XELOX or FOLFOX vs 5-FU/leucovorin (unadjusted HR = 0.94, P = .33; adjusted HR = 0.92, P = .23) or between capecitabine-based vs 5-FU-based treatment (unadjusted HR = 1.07, P = .26). A sensitivity analysis showed no difference between capecitabine vs XELOX (HR = 0.94, P = .50).

The investigators concluded: “Combination therapy with oxaliplatin provided consistently improved outcomes without adversely affecting post-relapse survival in the adjuvant treatment of stage III colon cancer, irrespective of whether the fluoropyrimidine backbone was capecitabine or leucovorin and [5-FU]. These data add to the existing evidence that oxaliplatin plus capecitabine or leucovorin and [5-FU] is the standard of care for the adjuvant treatment of stage III colon cancer, and offers physicians flexibility to treat patients according to the patients’ overall physical performance and preference.”

Hans-Joachim Schmoll, MD, of Martin Luther University, Halle, is the corresponding author for The Lancet Oncology article. Dr. Schmoll and Chris Twelves, MD, of Leeds Institute of Cancer and Pathology and St James’s University Hospital, contributed equally to the article.

The study was funded by Genentech Inc. For full disclosures of the study authors, visit

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.