Chemoprevention of esophageal adenocarcinoma

Abstract

Esophageal adenocarcinoma (EAC) is a major cause of cancer-related death, particularly in Western populations, and is rapidly rising in Asian populations at this time. Virtually all EACs develop from the precursor lesion Barrett’s esophagus (BE), which is the most significant risk factor for EAC. However, the rates of progression from BE to EAC are low and patients with BE are asymptomatic. Thus, any strategy for EAC prevention must carry a low risk of harm in order to be clinically useful. Since current EAC-screening and BE-surveillance methods carry some procedural risk and are burdensome, there is an opportunity for chemoprevention, i.e. medications or dietary factors that may prevent BE from progressing to EAC. A variety of candidate chemoprevention therapies have been assessed to date. Proton-pump inhibitors (PPIs) are the best studied and have modest EAC-chemoprevention efficacy in BE patients, with a recent randomized trial showing that high-dose PPI may be more effective than low-dose PPI. Aspirin and other non-steroidal anti-inflammatory drugs have moderate quality observational and randomized-trial evidence for preventing progression of BE to EAC, but their risks for harm have precluded their routine clinical use. Other therapies (statins, metformin, female sex hormones) generally do not have strong evidence to support their use in EAC chemoprevention. Although progress has been made in this field, there is still a need for more effective and safe chemoprevention therapies for EAC.

Chemopreventive Effects of Concomitant or Individual Use of Statins, Aspirin, Metformin, and Angiotensin Drugs: A Study Using Claims Data of 23 Million Individuals

“…The prostate cancer risk among statin users, as opposed to non-users, remains inconclusive, suggested to be reduced [ 5 ], increased [ 6 ], or not significantly associated with use of statins [ 7 ]. Aspirin, a cyclooxygenase and thromboxane inhibitor indicated for pain, inflammation, and CVDs, has shown associations with lowered risks of gastrointestinal cancers, including esophageal [ 8 , 9 ], stomach [ 10 ], liver [ 11 ], and colorectal [ 12 ] cancers. The chemopreventive effect of aspirin against pancreatic cancer could be nonsignificant [ 13 , 14 ] or marginal [ 15 ] in general, albeit significant in postmenopausal women [ 16 ].…”

Chronic acid-suppressant use and risk of Oesophageal cancer: protocol for a longitudinal study using a large population based cohort

“…COX inhibitors (which may lower OAC risk) 17 7. Metformin (which may lower OAC risk) 15 8. HRT (in female only, may lower OAC risk) 15 All predictor variables will be based on the latest coded information recorded in the GP record prior to entry to the cohort.…”

“…It also provides an opportunity to explore risks associated with long-term medication use. For example, we can explore risks associated with proton pump inhibitors which are used to treat chronic reflux symptoms which could also potentially mask development of oesophageal cancer; use of NSAIDs which tend to increase reflux symptoms and use of medications such as aspirin 14 15 or statins 15 which may lower risk of oesophageal cancer on their own or in combination with PPI 16 or cyclo-oxygenase inhibitors 15,17…”

Cancer Prevention in Patients with GERD and Barrett’s Esophagus—Medicine

“…Other agents include metformin, tamoxifen, ursodeoxycholic acid (UCDA), melatonin, and hormone replacement therapy. 120,121 For each of these drugs there are pharmacological activities suggesting a potential chemopreventive activity. The available evidence is however indirect and robust clinical data are lacking.…”