Statin Use and Survival with Early-Stage Hepatocellular Carcinoma

Jeon, Christie Y.; Goodman, Marc T.; Sundaram, Vinay

doi:10.1158/1055-9965.epi-15-1040

Cited by 15 publications

(15 citation statements)

References 21 publications

(24 reference statements)

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“…46 Immortal time bias occurs when there is a length of time between the start of follow-up and a subsequent start of statin therapy, which is counted in the total follow-up time for a participant—but during which the participant is actually unexposed—and, thus, it seems that this participant has survived longer than a control (nonstatin user). Jeon et al 47 show how this bias can spuriously create an association by using studies of patients with liver cancer in which the OS HR for statin use versus nonuse was 0.84 ( P = .047) before and 0.98 ( P = .82) after allowance for this bias. Randomized controlled trials, such as LUNGSTAR, avoid these issues.…”

Section: Discussionmentioning

confidence: 99%

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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Section: Discussionmentioning

confidence: 99%

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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“…Of these, 22 were further excluded because six studies did not include HCC patients, four studies did not valuate statin use as exposure, seven studies did not evaluate mortality or recurrence outcomes in HCC patients, two studies did not contain available data for the multivariate adjusted association between statin use and clinical outcomes in HCC patients, and the remaining three were abstracts of already included studies. Finally, nine studies were included [11][12][13][14][15][16][17]25,26].…”

Section: Literature Searchmentioning

confidence: 99%

“…Since two studies reported data according to HBV infection status of the patients [11,12], and one of them also reported stratified data according to the TNM stages of the tumor [11], these datasets were included separately. Overall, nine retrospective cohort studies including 62,273 HCC patients from China [11,12,16,25], Japan [14,15], Korea [26], and the United States [13,17] were included. The mean age of the included patients varied from 54 to 67 years, with proportions of male ranging from 64% to 99%.…”

Section: Study Characteristics and Quality Evaluationmentioning

confidence: 99%

Statin use and the prognosis of patients with hepatocellular carcinoma: a meta-analysis

Li¹,

Liu²,

Hu³

2020

Bioscience Reports

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Background: Association between statin use and prognosis in patients with hepatocellular carcinoma (HCC) remains unknown. We performed a meta-analysis of follow-up studies to systematically evaluate the influence of statin use on clinical outcome in HCC patients. Methods: Studies were obtained via systematic search of PubMed, Cochrane’s Library, and Embase databases. A randomized-effect model was used to pool the results. Subgroup analyses were performed to evaluate the influence of study characteristics on the association. Results: Nine retrospective cohort studies were included. Overall, statin use was associated with a reduced all-cause mortality in HCC patients (risk ratio [RR]: 0.81, 95% CI: 0.74–0.88, P < 0.001; I2 = 63%). Subgroup analyses showed similar results for patients with stage I-III HCC (RR: 0.83, 0.79, and 0.90 respectively, P all < 0.01) and patients after palliative therapy for HCC (RR: 0.80, P < 0.001), but not for patents with stage IV HCC (RR: 0.91, P = 0.28) or those after curative therapy (RR: 0.92, P = 0.20). However, the different between subgroups were not significant (both P > 0.05). Moreover, statin use was associated with reduced HCC-related mortality (RR: 0.78, P = 0.001) in overall patient population and HCC recurrence in patients after curative therapies (RR: 0.55, P < 0.001). Conclusions: Satin use is associated with reduced mortality and recurrence of HCC. These results should be validated in prospective cohort studies and randomized controlled trials.

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“…The data in this context are limited and controversial. While recently published findings analyzing early stage HCC patients showed no significant difference in survival related to statin treatment (20), the additional effect of statins on chemotherapy as well as transarterial chemoembolization (TACE) treatment could be beneficial in HCC patients (22).…”

mentioning

confidence: 99%

Rationale for the use of statins in liver disease

Schierwagen

Uschner

Magdaleno

et al. 2017

American Journal of Physiology-Gastrointestinal and Liver Physi

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The evolution of chronic liver injuries from benign and manageable dysfunction to life threatening end-stage liver disease with severe complications renders chronic liver disease a global health burden. Because of the lack of effective medication, transplantation remains the only and final curative option for end-stage liver disease. Since the demand for organ transplants by far exceeds the supply, other treatment options are urgently required to prevent progression and improve end-stage liver disease. Statins are primarily cholesterol-lowering drugs used for primary or secondary prevention of cardiovascular diseases. In addition to the primary effect, statins act beneficially through different pleiotropic mechanisms on inflammation, fibrosis, endothelial function, thrombosis, and coagulation to improve chronic liver diseases. However, concerns remain about the efficacy and safety of statin treatment because of their potential hepatotoxic risks, and as of now, these risks impede broader use of statins in the treatment of chronic liver diseases. The aim of this review is to comprehensively describe the mechanisms by which statins improve prospects for different chronic liver diseases with special focus on the pathophysiological rationale and the clinical experience of statin use in the treatment of liver diseases.

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Statin Use and Survival with Early-Stage Hepatocellular Carcinoma

Cited by 15 publications

References 21 publications

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

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

Statin use and the prognosis of patients with hepatocellular carcinoma: a meta-analysis

Rationale for the use of statins in liver disease

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