The effect of NSAIDs on tumor response and prognosis of stage IV colorectal cancer

Abstract

Background: Colorectal cancer (CRC) is the third most frequent cancer in Korea, and it is continuously increasing in prevalence. Despite improved survival rates, the five-year survival in stage IV CRC is less than 10%. There have been many studies which have suggested that there is a protective and adjuvant therapeutic effect on CRC from the regular use of non-steroidal anti-inflammatory drugs (NSAIDs) including aspirin. However, recently accumulating data suggest that CRCs have different responses to NSAIDs, depending on the timing of initiation, duration of therapy or target groups. In particular, the data about the effect of NSAIDs on stage IV CRC patients have been limited. The aim of this study was to evaluate the effect of NSAIDs on tumor response and prognosis of stage IV CRC.Methods: From January 2005 to December 2010, patients who were diagnosed with stage IV CRC and received chemotherapy at Severance Hospital and who had underlying hypertension (HTN), coronary artery disease (CAD), angina or rheumatoid arthritis (RA) (diseases associated with NSAID use) were recruited, and their medical records were retrospectively analyzed. The NSAIDs non-user group was defined as never having used NSAIDs or patients who took NSAIDs for less than one month, and the prediagnostic NSAID-user group was defined as patients who took NSAIDs over the 12 consecutive months before diagnosis with stage IV CRC. The two groups were compared in terms of baseline characteristics, tumor response, overall survival (OS), cancer-specific survival (CSS), progression-free survival (PFS) and disease-free survival (DFS).Results: Compared with the NSAID non-user group (N=137), the prediagnostic NSAID-user group (N=29) was not different in terms of baseline characteristics, except for CAD prevalence, which was higher in the prediagnostic NSAID-user group (p=0.004). There was no significant difference in tumor response between the NSAID non-user group and the prediagnostic NSAID-user group based on use of NSAIDs during chemotherapy (p=0.304). The OS, PFS and DFS were significantly different in univariate analysis between the NSAID non-user group and the prediagnostic NSAID-user group (OS: 20.48 months vs. 27.03 months, p=0.035, PFS: 8.55 months vs. 13.26 months, p=0.048, DFS: 11.20 months vs. 25.60 months, p=0.031). In multivariate analysis, the OS and CSS of the NSAID non-user group were better than those of the prediagnostic NSAID-user group (overall mortality: HR, 0.478; 95% CI 0.234-0.974; p=0.042, cancer-specific mortality: HR, 0.386; 95% CI 0.163-0.910; p=0.030). Conclusion: Long-term NSAID use before diagnosis with stage IV CRC could be a negative prognostic factor.