Association Between Statin Use After Diagnosis of Esophageal Cancer and Survival: A Population-Based Cohort Study

Alexandre, Leo; Clark, Allan; Bhutta, Hina Y.; Chan, Simon; Lewis, Michael P.; Hart, Andrew

doi:10.1053/j.gastro.2015.12.039

Cited by 45 publications

(47 citation statements)

References 25 publications

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“…The only previous study (9) to investigate statin use after diagnosis and esophageal cancerspecific mortality used Clinical Practice Research Datalink data from England (based upon GP prescribing data and linked cancer registry data and national mortality data). This study concluded that statins were associated with large and significant reductions in esophageal cancer specific mortality.…”

Section: Discussionmentioning

confidence: 99%

“…The only previous epidemiological study to investigate statin use after diagnosis in esophageal cancer patients concluded that statins were associated with large and significant reductions in cancer-specific and all-cause mortality. (9) The association between statin use and esophageal cancer-specific mortality is of importance because it will inform the decision to conduct clinical trials of statins as adjuvant cancer therapy in esophageal cancer patients. Therefore, to clarify this association we investigated whether statin use after cancer diagnosis was associated with reduced esophageal cancerspecific and all-cause mortality in a population-based cohort of esophageal cancer patients.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Statin use after esophageal cancer diagnosis and survival: A population based cohort study

Cardwell

Spence

Hughes

et al. 2017

Cancer Epidemiology

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Statin use after esophageal cancer diagnosis and survival: A population based cohort study

Cardwell

Spence

Hughes

et al. 2017

Cancer Epidemiology

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“…Specifically, Statins, well-known inhibitors of HMGCR, have been clinically correlated to prolonged survival expectancy among cancer sufferers, such as endometrial cancer [155] and esophageal adenocarcinoma [156]. Moreover, lower risk of tumor initiation or dissemination have been observed in a variety of cancer types following the administration of Statins, revealing a great possibility to expand its therapeutic indications towards tumorous field.…”

Section: Functions Of Ampk Signaling Components In Tumorigenesismentioning

confidence: 99%

Functional characterization of AMP-activated protein kinase signaling in tumorigenesis

Cheng

Zhang

et al. 2016

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

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AMP-activated protein kinase (AMPK) is a ubiquitously expressed metabolic sensor among various species. Specifically, cellular AMPK is phosphorylated and activated under certain stressful conditions, such as energy deprivation, in turn to activate diversified downstream substrates to modulate the adaptive changes and maintain metabolic homeostasis. Recently, emerging evidences have implicated the potential roles of AMPK signaling in tumor initiation and progression. Nevertheless, a comprehensive description on such topic is still in scarcity, especially in combination of its biochemical features with mouse modeling results to elucidate the physiological role of AMPK signaling in tumorigenesis. Hence, we performed this thorough review by summarizing the tumorigenic role of each component along the AMPK signaling, comprising of both its upstream and downstream effectors. Moreover, their functional interplay with the AMPK heterotrimer and exclusive efficacies in carcinogenesis were chiefly explained among genetically altered mice models. Importantly, the pharmaceutical investigations of AMPK relevant medications have also been highlighted. In summary, in this review, we not only elucidate the potential functions of AMPK signaling pathway in governing tumorigenesis, but also potentiate the future targeted strategy aiming for better treatment of aberrant metabolism-associated diseases, including cancer.

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“…The magnitude of the effects found by these studies, along with study size, show why they attracted attention: a 22% reduction in cancer deaths among 146,326 women, 13 no effect on breast cancer incidence among 79,518 women, 14 40% reduction in prostate deaths among 22,110 high-risk patients with prostate cancer, 15 14% reduction in all-cause mortality in 2,142 patients with pancreatic cancer, 16 18% reduction in recurrence and/or deaths in 8,010 patients with breast cancer, 17 and 29% reduction in breast cancer mortality from a meta-analysis of 12 studies covering 87,951 patients with breast cancer. 18 There have also been other large studies that have reported that statins, usually when still taken after diagnosis, can reduce recurrence or mortality in patients with esophageal, 19 colorectal, 20 and lung cancer, 21 and all tumors combined, 22 with further evidence from meta-analyses of all cancers, 23 and prostate (postradiotherapy) 24,25 and colorectal cancer. 26 However, all studies were observational and none established a dose-response for statin efficacy.…”

Section: Introductionmentioning

confidence: 98%

Multicenter, Phase III, Randomized, Double-Blind, Placebo-Controlled Trial of Pravastatin Added to First-Line Standard Chemotherapy in Small-Cell Lung Cancer (LUNGSTAR)

Seckl

Ottensmeier

Cullen

et al. 2017

JCO

111

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PurposeTreating small-cell lung cancer (SCLC) remains a therapeutic challenge. Experimental studies show that statins exert additive effects with agents, such as cisplatin, to impair tumor growth, and observational studies suggest that statins combined with anticancer therapies delay relapse and prolong life in several cancer types. To our knowledge, we report the first large, randomized, placebo-controlled, double-blind trial of a statin with standard-of-care for patients with cancer, specifically SCLC.Patients and MethodsPatients with confirmed SCLC (limited or extensive disease) and performance status 0 to 3 were randomly assigned to receive daily pravastatin 40 mg or placebo, combined with up to six cycles of etoposide plus cisplatin or carboplatin every 3 weeks, until disease progression or intolerable toxicity. Primary end point was overall survival (OS), and secondary end points were progression-free survival (PFS), response rate, and toxicity.ResultsEight hundred forty-six patients from 91 United Kingdom hospitals were recruited. The median age of recruited patients was 64 years of age, 43% had limited disease, and 57% had extensive disease. There were 758 deaths and 787 PFS events. No benefit was found for pravastatin, either in all patients or in several subgroups. For pravastatin versus placebo, the 2-year OS rate was 13.2% (95% CI, 10.0 to 16.7) versus 14.1% (95% CI, 10.9 to 17.7), respectively, with a hazard ratio of 1.01 (95% CI, 0.88 to 1.16; P = .90. The median OS was 10.7 months v 10.6 months, respectively. The median PFS was 7.7 months v 7.3 months, respectively. The median OS (pravastatin v placebo) was 14.6 months in both groups for limited disease and 9.1 months versus 8.8 months, respectively, for extensive disease. Adverse events were similar between groups.ConclusionPravastatin 40 mg combined with standard SCLC therapy, although safe, does not benefit patients. Our conclusions are the same as those found in all four much smaller, randomized, placebo-controlled trials specifically designed to evaluate statin therapy in patients with cancer.

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Association Between Statin Use After Diagnosis of Esophageal Cancer and Survival: A Population-Based Cohort Study

Cited by 45 publications

References 25 publications

Statin use after esophageal cancer diagnosis and survival: A population based cohort study

Statin use after esophageal cancer diagnosis and survival: A population based cohort study

Functional characterization of AMP-activated protein kinase signaling in tumorigenesis

Multicenter, Phase III, Randomized, Double-Blind, Placebo-Controlled Trial of Pravastatin Added to First-Line Standard Chemotherapy in Small-Cell Lung Cancer (LUNGSTAR)

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