Aspirin, metformin and statins: Promising targeted adjuncts in rectal cancer
Aspirin, metformin and statins demonstrate utility as adjuncts to neoadjuvant treatment in rectal cancer, resulting in increased downstaging of rectal tumours, according to a recent study.
Researchers performed a systematic literature search of studies investigating the use of drugs to enhance response to neoadjuvant radiation in rectal cancer. Of the 2,137 studies identified, only nine studies were included in the final review. A narrative review was conducted due to the limited number of randomized controlled trials and the heterogeneity of relevant trials.
Results showed that the use of statins or aspirin during neoadjuvant therapy led to a significantly higher rate of tumour downstaging. Statins particularly emerged as a significant predictor of complete tumour response, whereas aspirin was associated with a greater 5-year progression-free survival and overall survival.
Meanwhile, metformin use was associated with a significantly higher overall and disease-free survival, especially in a subset of rectal cancer patients with diabetes.
The results highlight a clear need for prospective randomized controlled trials to determine the true impact of statins, aspirin and metformin as adjuncts, singularly or in combination, and whether they confer an increase in response to neoadjuvant therapy or a long-term effect on survival, researchers said.
In rectal cancer, complete tumour response to neoadjuvant chemoradiotherapy has been reported to reduce the risk of local recurrence and improve disease-free and overall survival. However, such response is achieved in only 20 to 30 percent of patients. [Dis Colon Rectum 2015;58:32–44; J Clin Oncol 2009;27:5124–5130; Surg Oncol Clin N Am 2010;19:829–845]
Optimizing response to treatment is now fundamental to improving outcomes from rectal cancer, in both early and locally advanced stages, especially because malignancies (as they develop) acquire both epigenetic and genetic changes that promote therapy resistance and evasion of apoptosis—an important hallmark of cancer. [Br J Surg 2014;101:1299–1309; Cell 2011;144:646–674]