Abstract
BackgroundPre-clinical studies have shown that furosemide slows cancer cell growth by acting on the Na-K-2Cl transporter, particularly for gastric cancer cells. However, epidemiological studies have not investigated furosemide use and mortality in gastroesophageal cancer patients. Consequently, we conducted a population-based study to investigate whether furosemide use is associated with reduced cancer-specific mortality in esophageal/gastric cancer patients.MethodsA cohort of patients newly diagnosed with esophageal or gastric cancer between 1998 and 2013 were identified from English cancer registries and linked to the Clinical Practice Research Datalink to provide prescription records and the Office of National Statistics to provide death data up to September 2015. Time-dependant Cox-regression models were used to calculate hazard ratios (HRs) comparing cancer-specific mortality in furosemide users with non-users. Analyses were repeated restricting to patients with common furosemide indications (heart failure, myocardial infarction, edema or hypertension) to reduce potential confounding.ResultsThe cohort contained 2708 esophageal cancer patients and 2377 gastric cancer patients, amongst whom 1844 and 1467 cancer-specific deaths occurred, respectively. Furosemide use was not associated with reduced cancer-specific mortality overall (adjusted HR in esophageal cancer = 1.28, 95% CI 1.10, 1.50 and in gastric cancer = 1.27, 95% CI 1.08, 1.50) or when restricted to patients with furosemide indications before cancer diagnosis (adjusted HR in esophageal cancer = 1.07, 95% CI 0.88, 1.30 and in gastric cancer = 1.18, 95% CI 0.96, 1.46).ConclusionsIn this large population-based cohort study, furosemide was not associated with reduced cancer-specific mortality in patients with esophageal or gastric cancer.
Highlights
Pre-clinical studies have shown that furosemide slows cancer cell growth by acting on the Na-K-2Cl transporter, for gastric cancer cells
Liu et al BMC Cancer (2019) 19:1017 found with two subtypes, ubiquitous NKCC1 and kidney-specific NKCC2, both of which are sensitive to furosemide [9]
An in-vitro cell study found that NKCC1 expression was three times higher in poorly differentiated compared with moderately differentiated gastric adenocarcinoma cells [12]
Summary
Pre-clinical studies have shown that furosemide slows cancer cell growth by acting on the Na-K-2Cl transporter, for gastric cancer cells. We conducted a population-based study to investigate whether furosemide use is associated with reduced cancer-specific mortality in esophageal/gastric cancer patients. This study showed that furosemide reduced cell growth in poorly differentiated gastric adenocarcinoma cells, and suggested this action was via the inhibition of NKCC [12]. NKCC1 was found to have higher expression in more poorly differentiated esophageal squamous-cell carcinoma (SCC) cases and depletion of NKCC1 inhibited cell proliferation [13]. Despite this preclinical evidence suggesting furosemide could slow gastroesophageal cancer progression, no studies have been conducted to investigate a potential association in humans
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