Evidence of Recurrence-Free, Disease-Free, and Overall Survival Benefit of Aspirin and COX‑2 Inhibitor Use in Stage III Colon Cancer


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Kimmie Ng, MD, MPH

Aspirin/COX-2 Inhibitors and Colon Cancer

[T]his observational study of stage III colon cancer patients found statistically significant associations between aspirin and COX-2 inhibitor use and reduced cancer recurrence and mortality…. Further exploration of predictive biomarkers of aspirin and COX-2 inhibitor activity is warranted.

—Kimmie Ng, MD, MPH, and colleagues

In an analysis from the Cancer and Leukemia Group B (CALGB) 89803 adjuvant trial reported in the Journal of the National Cancer Institute, Kimmie Ng, MD, MPH, of Dana-Farber Cancer Institute, Boston, and colleagues found consistent trends suggesting benefit of aspirin use and cyclo-oxygenase-2 (COX-2) inhibitor use on recurrence-free, disease-free, and overall survival in patients with stage III colon cancer.1

Study Details

This prospective observational study involved 799 patients in the CALGB 89803 trial evaluating the addition of irinotecan to adjuvant fluorouracil-leucovorin. The trial showed no difference in outcomes between the study groups.

A self-administered questionnaire assessing diet, lifestyle, and medication use was conducted midway through chemotherapy and 6 months after chemotherapy. In the current analysis, consistent aspirin use was defined as any aspirin use reported at both time points, and COX-2 inhibitor use was defined as any use reported at the second time point.

Multivariate analysis was adjusted for age (continuous variable), sex, race, adjuvant treatment in the trial, family history of colorectal cancer, performance status, depth of tumor invasion through the bowel wall, number of positive lymph nodes, tumor grade, body mass index at 6 months after chemotherapy, and physical activity at 6 months after chemotherapy.

Overall, 9.4% of patients were aspirin users and 7.0% were COX-2 inhibitor users. Aspirin users were older and more likely to be male, and COX-2 inhibitor users were less likely to have a family history of cancer, had higher body mass index, and reported more acetaminophen use.

Aspirin Use

Recurrence-free, disease-free, and overall mortality events were observed in 182, 214, and 156 of 724 patients with nonconsistent aspirin use and in 12, 19, and 14 of 75 consistent aspirin users. On multivariate analysis, hazard ratios (HRs) for consistent aspirin use vs nonconsistent use were 0.51 (95% confidence interval [CI] = 0.28–0.95) for recurrence-free survival, 0.68 (95% CI = 0.42–1.11) for disease-free survival, and 0.63 (95% CI = 0.35–1.12) for overall survival. In an analysis censored at 5 years to minimize the effects of noncancer deaths, hazard ratios were 0.61 (95% CI = 0.36–1.04) for disease-free survival and 0.48 (95% CI = 0.23–0.99) for overall survival.

COX-2 Inhibitor Use

Recurrence-free, disease-free, and overall mortality events were observed in 198, 237, and 179 of 784 patients not using COX-2 inhibitors and in 9, 12, and 7 of 59 COX-2 inhibitor users. On multivariate analysis, hazard ratios for COX-2 inhibitor users vs nonusers were 0.53 (95% CI = 0.27–1.04) for recurrence-free survival, 0.60 (95% CI = 0.33–1.08) for disease-free survival, and 0.50 (95% CI = 0.23-1.07) for overall survival. In an analysis censored at 5 years, hazard ratios were 0.47 (95% CI = 0.24–0.91) for disease-free survival and 0.26 (95% CI = 0.08–0.81) for overall survival.

The ongoing phase III Alliance for Clinical Trials in Oncology CALGB 80702 trial and the Aspirin for Dukes C and High Risk Dukes B Colorectal Cancers study (ASCOLT) are examining the effects of celecoxib and aspirin in colorectal cancer, but results will not be available for several years.

The investigators concluded: “This observational study of stage III colon cancer patients found statistically significant associations between aspirin and COX-2 inhibitor use and reduced cancer recurrence and mortality. Results from the ongoing CALGB 80702 and ASCOLT trials are eagerly awaited. Further exploration of predictive biomarkers of aspirin and COX-2 inhibitor activity is warranted.” ■

Disclosure: The study was supported by the National Cancer Institute, Conquer Cancer Foundation of the American Society of Clinical Oncology, Damon Runyan Cancer Research Foundation, and the Pharmacia and Upjohn Company, now Pfizer Oncology. For full disclosures of the study authors, visit jnci.oxfordjournals.org.

Reference

1. Ng K, Meyerhardt JA, Chan AT, et al: Aspirin and COX-2 inhibitor use in patients with stage III colon cancer. J Natl Cancer Inst 107(1):dju345, 2015.

Alfred I. Neugut, MD, PhD, of the Herbert Irving Comprehensive Cancer Center, Columbia University College of Physicians and Surgeons, offers his perspective on the CALGB 89803 trial discussed above.


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