Long-Term Survival Results of Surgery Alone Versus Surgery Plus 5-Fluorouracil and Leucovorin for Stage II and Stage III Colon Cancer: Pooled Analysis of NSABP C-01 Through C-05. A Baseline from Which to Compare Modern Adjuvant Trials

Neal W. Wilkinson MD, MPH, Greg Yothers PhD, Samia Lopa MS, Joseph P. Costantino DrPH, Nicholas J. Petrelli MD, Norman Wolmark MD
Colorectal Cancer
Volume 17, Issue 4 / April , 2010

View full article HTML | View full article PDF | Download Citation

Abstract

Background

The objective of this study is to conduct a pooled analysis of National Surgical Adjuvant Breast and Bowel Project (NSABP) colon trials involving surgery and surgery plus 5-fluorouracil and leucovorin (5-FU/LV) to compare survival and establish a baseline from which to evaluate future studies.

Methods

All patients enrolled in NSABP adjuvant trials C-01 through C-05 with stage II and III disease who were treated with surgery or with surgery plus 5-FU/LV were examined for overall survival (OS), disease-free survival (DFS), and recurrence-free interval (RFI). Time-to-event by treatment group was examined using adjusted Kaplan–Meier estimates and multivariable Cox regression analysis.

Results

There were 2,966 eligible patients: 693 (23%) surgery and 2,273 (77%) surgery plus 5-FU/LV; 1,255 (42%) stage II and 1,711 (58%) stage III. Age ≥60 years [hazard ratio (HR) = 1.36, P < 0.0001], male gender (HR = 1.20, P = 0.0012), and more nodes positive or fewer nodes examined (P < 0.0001) were associated with worse survival. At 5 years, the adjusted OS was 0.62 [confidence interval (CI) = 0.60–0.63] in the surgery group and 0.76 (CI = 0.74–0.78) in the surgery plus 5-FU/LV group. Treatment with 5-FU/LV was associated with improved outcome compared with surgery: OS (HR = 0.62, P < 0.0001), DFS (HR = 0.66, P < 0.0001) and RFI (HR = 0.64, P < 0.0001). Improved OS with adjuvant treatment was seen in both stage II (HR = 0.58, 95% CI = 0.48–0.71) and stage III disease (HR = 0.65, 95% CI = 0.55–0.75).

Conclusions

This analysis demonstrates that treatment of colon cancer patients with 5-FU/LV following surgery provides benefit over surgery alone and can provide anticipated survival outcomes with which to compare modern adjuvant trials.

Go to Issue Contents