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Aspirin as adjuvant therapy for colorectal cancer—reinterpreting paradigms

Abstract

A high-quality body of evidence supports the use of aspirin in reducing sporadic and hereditary adenomatous polyps, and numerous observational studies point to a reduction in colorectal cancer (CRC) risk. However, using aspirin as an adjuvant therapy in established CRC was until recently inconceivable. Now, evidence from both observational and clinical trials of aspirin for other indications suggests that aspirin initiation after (or before) the diagnosis of CRC improves CRC-specific mortality. These exciting findings need to be confirmed in prospective randomized trials that are underway. The recent failure of adjuvant irinotecan, bevacizumab, and cetuximab clinical trials compels us to reconsider our assumptions and paradigms for treating CRC. In this Review, we summarize clinical and preclinical evidence supporting aspirin use in established CRC and outline a framework for better understanding aspirin activity in the pathogenesis of CRC. We describe the data supporting adjuvant aspirin in resected CRC, including the issues of dose, duration and toxicity, and discuss potential biomarkers that may help better select patients for aspirin therapy.

Key Points

  • Aspirin has an inverse association with colorectal cancer, and randomized placebo-controlled trials support the benefit of aspirin in reducing polyp burden

  • Recent observational and randomized studies with vascular end points have strongly indicated an adjuvant effect of aspirin in established cancers

  • Benefit is seen with doses as low as 80 mg daily, and magnitude of benefit is between 20% and 40%

  • Benefit seems to be greater for disease in the proximal bowel and when patients did not receive aspirin prior to cancer diagnosis

  • No benefit has been observed for other non-steroidal anti-inflammatory drugs

  • Prospective randomized adjuvant clinical trials are urgently required; one has been initiated and several more are being planned

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Figure 1: Aspirin exerts activity at multiple points along the colorectal carcinogenesis pathway.
Figure 2: Observational and randomized studies that do not stratify for aspirin use before cancer diagnosis may be vulnerable to confounding, due to development of biologically indolent tumours with lower metastatic potential.

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Acknowledgements

This review is written on behalf of the ASCOLT study group, which is currently undertaking a randomized adjuvant aspirin study in Asia.

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Correspondence to Whay Kuang Chia.

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Chia, W., Ali, R. & Toh, H. Aspirin as adjuvant therapy for colorectal cancer—reinterpreting paradigms. Nat Rev Clin Oncol 9, 561–570 (2012). https://doi.org/10.1038/nrclinonc.2012.137

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