Aspirin and cancer: has aspirin been overlooked as an adjuvant therapy?

Abstract

Aspirin inhibits the enzyme cyclooxygenase (Cox), and there is a significant body of epidemiological evidence demonstrating that regular aspirin use is associated with a decreased incidence of developing cancer. Interest focussed on selective Cox-2 inhibitors both as cancer prevention agents and as therapeutic agents in patients with proven malignancy until concerns were raised about their toxicity profile. Aspirin has several additional mechanisms of action that may contribute to its anti-cancer effect. It also influences cellular processes such as apoptosis and angiogenesis that are crucial for the development and growth of malignancies. Evidence suggests that these effects can occur through Cox-independent pathways questioning the rationale of focussing on Cox-2 inhibition alone as an anti-cancer strategy. Randomised studies with aspirin primarily designed to prevent cardiovascular disease have demonstrated a reduction in cancer deaths with long-term follow-up. Concerns about toxicity, particularly serious haemorrhage, have limited the use of aspirin as a cancer prevention agent, but recent epidemiological evidence demonstrating regular aspirin use after a diagnosis of cancer improves outcomes suggests that it may have a role in the adjuvant setting where the risk:benefit ratio will be different.

Figure 1

Aspirin mechanisms of action and pathophysiological effects. Black block arrows indicate known mechanisms. Dotted black arrows indicate potential mechanisms that could contribute to anti-cancer effects. Cox=cyclooxygenase; NFκB=nuclear factor-κB.

Figure 2

(A–C) Randomised trials of aspirin vs no aspirin/placebo in which colorectal cancer outcomes are available. (A) Includes trials designed to assess aspirin as a primary prevention agent against cancer and the first evidence from the long-term follow-up of trials primarily designed to improve cardiovascular outcomes. (B) Includes recent data from a meta-analysis of cardiovascular trials from which cancer incidence data were obtained. (C) Trials designed as secondary prevention against colorectal cancer. (D) Trials in which aspirin was used as a therapeutic agent against cancer with overall survival as the primary outcome measure. Details of the trials are given in Table 1.