Journal
BRITISH JOURNAL OF CANCER
Volume 117, Issue 2, Pages 210-219Publisher
SPRINGERNATURE
DOI: 10.1038/bjc.2017.175
Keywords
colorectal cancer; radiotherapy; adjunct; tumour regression; therapy response; aspirin; statins; metformin
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Funding
- Royal College of Surgeons of England Research Scholarship - Rosetrees Trust
- MRC Clinical Research Training Fellowship
- The David Telling Charitable Trust
- The Above & Beyond Charitable Trust
- John James Foundation
- Cancer Research UK
- MRC [MR/N001494/1] Funding Source: UKRI
- Cancer Research UK [11975] Funding Source: researchfish
- Medical Research Council [MR/N001494/1] Funding Source: researchfish
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Background: Complete tumour response (pCR) to neo-adjuvant chemo-radiotherapy for rectal cancer is associated with a reduction in local recurrence and improved disease-free and overall survival, but is achieved in only 20-30% of patients. Drug repurposing for anti-cancer treatments is gaining momentum, but the potential of such drugs as adjuncts, to increase tumour response to chemo-radiotherapy in rectal cancer, is only just beginning to be recognised. Methods: A systematic literature search was conducted and all studies investigating the use of drugs to enhance response to neoadjuvant radiation in rectal cancer were included. 2137 studies were identified and following review 12 studies were extracted for full text review, 9 studies were included in the final analysis. Results: The use of statins or aspirin during neo-adjuvant therapy was associated with a significantly higher rate of tumour downstaging. Statins were identified as a significant predictor of pCR and aspirin users had a greater 5-year progression-free survival and overall survival. Metformin use was associated with a significantly higher overall and disease-free survival, in a subset of diabetic patients. Conclusions: Aspirin, metformin and statins are associated with increased downstaging of rectal tumours and thus may have a role as adjuncts to neoadjuvant treatment, highlighting a clear need for prospective randomised controlled trials to determine their true impact on tumour response and overall survival.
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