Adjuvant capecitabine plus oxaliplatin more effective than 5-FU and leucovorin in improving
disease-free survival in patients of all ages, including those 70 and older

A randomized phase III study has shown that post-surgical (adjuvant) treatment with the capecitabine and
oxaliplatin (a combination called XELOX) is more effective than standard 5-fluorouracil and leucovorin
(5-FU/LV) therapy for slowing the progression of stage III colon cancer among patients of all ages,
including those age 70 and older. Previous data have suggested that older patients may not benefit from or
be able to tolerate aggressive adjuvant treatment with newer chemotherapy drugs, beyond 5FU/LV.

“These findings indicate that patients with stage III colon cancer benefit more from the newer, XELOX
adjuvant treatment regimen than from traditional adjuvant chemotherapy, and that this benefit persists
among older patients. While treatment decisions should be made on an individual basis, these findings
shed important new light on how we can best treat otherwise healthy patients age 70 and older,” said lead
author Daniel G. Haller, MD, Professor of Medicine and Deenie Greitzer Professor of Gastrointestinal
Oncology at the Abramson Cancer Center at the University of Pennsylvania.

In this study, 1,886 patients with stage III colon cancer were randomly assigned to receive XELOX or 5-
FU/LV chemotherapy following surgery. After 3 years, 71 percent of patients in the XELOX group did
not experience disease progression compared with 67 percent of the 5-FU/LV group, a difference that was
statistically significant. Among patients younger than 70, 72 percent of patients in the XELOX group did
not experience disease progression after three years versus 69 percent of those in the 5-FU/LV group. The
corresponding figures for patients age 70 and older were 66 percent and 60 percent, respectively. Analysis
of overall survival is ongoing.

The use of newer chemotherapy drugs in the adjuvant setting for older patients with stage III colon cancer
has been a topic of controversy, and these findings contradict conclusions from two recent studies. The
first, a 2009 retrospective meta-analysis of six clinical trials, found that elderly patients with stage III
colon cancer did not experience improved disease-free survival or longer overall survival after receiving
therapy that included newer drugs such as oxaliplatin, irinotecan and capecitabine, compared to 5FU/LV
controls. In addition, the prospective MOSAIC trial recently reported that adjuvant treatment with
oxaliplatin and 5-FU/LV did not provide additional benefit for elderly patients.

These data have prompted some clinicians to decide against using these drugs for their older patients. In addition, German clinical guidelines were amended based on these previous studies, and a European trial examining
adjuvant treatment for colorectal cancer – PETACC-8 – was amended to exclude patients over age 70.
According to the authors of the current study, these new data are strong enough to recommend that patients should be evaluated on an individual basis for XELOX therapy, regardless of age.



Source: 2010 Gastrointestinal Cancers Symposium