XELOX Improves Survival in Elderly with Colorectal Cancer

ORLANDO, FL — Although advanced age is the greatest single risk factor for colorectal cancer, with more than 90% of cases diagnosed in individuals 50 years and older, these patients often are not given the same treatment options as their younger counterparts. This disparity in treatment has largely resulted from two recent studies that showed no benefit with newer chemotherapy drugs in the adjuvant setting for older patients (≥70 years) with stage III colon cancer.

The first study, which was presented in a poster session at the 2009 Annual American Society of Clinical Oncology Meeting, was a retrospective meta-analysis of six clinical trials that 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 with 5-FU and leucovorin. The second is the MOSAIC (Multi-center InternationalStudy of Oxaliplatin/5-Fluorouracil/Leucovorin in the AdjuvantTreatment of Colon Cancer) trial, which had reported that the addition of oxaliplatin to a 5-FU and leucovorin regimen did not provide additional benefit for elderly patients. Based on these data, some clinicians have opted not to use these drugs for their older patients with colorectal cancer, and some colorectal cancer trials have been amended to exclude patients over age 70; however, a study presented at the 2010 Gastrointestinal Cancers Symposium by Daniel G. Haller, MD, professor of medicine and Deenie Greitzer professor of gastrointestinal oncology at the Abramson Cancer Center at the University of Pennsylvania may change this.

Haller and colleagues conducted a subgroup analysis based on age of the NO16968 (XELOXA) study, which represents one of the largest trials in the adjuvant setting. In this study, 1886 patients with lymph-node positive, stage III colorectal cancer were randomized to XELOX or intravenous 5-FU plus leucovorin postoperatively. The study found that XELOX significantly improved disease-free survival, which was the primary endpoint, with 70.9% of patients being disease-free at 3 years compared with 66.5% of those receiving standard therapy. Analyses of patients 65 years and older and 70 years and older revealed that XELOX efficacy was maintained regardless of age (Table

).

3-year DFS

3-year DFS

XELOX

5-FU/leucovorin

HR (95% CI)

< 65 years (n = 1142)

72%

69%

0.80 (0.65-0.98)

≥ 65 years (n = 744)

68%

62%

0.81 (0.64-1.03)

< 70 years (n = 1477)

72%

69%

0.79 (0.66-0.94)

≥ 70 years (n = 409)

66%

60%

0.87 (0.63-1.18)

CI indicates confidence interval; DFS = disease-free survival; HR = hazard ratio

Haller noted that these findings confirm the benefits shown with oxaliplatin plus 5-FU combinations in stage III patients in the MOSAIC and NSABP (National Surgical Adjuvant Breast and Bowel Project) C-07 trials, but unlike the MOSAIC trial, the benefits appear to be maintained even in those older than 70 years. “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 Haller.

Overall survival data are currently immature, but trends for superiority of XELOX are present in all age groups analyzed, noted Haller. Follow-up assessments are ongoing and further results are expected to be reported at various congresses throughout 2010.

2010 GI Cancers Symposium Abstract 284