Potentiating the effects of radiotherapy in rectal cancer: the role of aspirin, statins and metformin as adjuncts to therapy
Abstract
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 neo-adjuvant 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.
How strong is the evidence?
Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid.
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