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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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Title: Multicenter, Phase III, Randomized, Double-Blind, Placebo-Controlled Trial of Pravastatin Added to First-Line Standard Chemotherapy in Small-Cell Lung Cancer (LUNGSTAR)
Authors: Seckl, MJ
Ottensmeier, CH
Cullen, M
Schmid, P
Ngai, Y
Muthukumar, D
Thompson, J
Harden, S
Middleton, G
Fife, KM
Crosse, B
Taylor, P
Nash, S
Hackshaw, A
Item Type: Journal Article
Abstract: Purpose Treating 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 Methods Patients 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 progressionfree survival (PFS), response rate, and toxicity. Results Eight 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. Conclusion Pravastatin 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, placebocontrolled trials specifically designed to evaluate statin therapy in patients with cancer.
Issue Date: 27-Feb-2017
Date of Acceptance: 27-Feb-2017
URI: http://hdl.handle.net/10044/1/54190
DOI: https://dx.doi.org/10.1200/JCO.2016.69.7391
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology
Start Page: 1506
End Page: 1514
Journal / Book Title: Journal of Clinical Oncology
Volume: 35
Issue: 14
Copyright Statement: © 2017 by American Society of Clinical Oncology. Licensed under the Creative Commons Attribution 4.0 License
Sponsor/Funder: Imperial College Healthcare NHS Trust- BRC Funding
Funder's Grant Number: RDB01 79560
Keywords: Science & Technology
Life Sciences & Biomedicine
Oncology
POPULATION-BASED COHORT
STATIN USE
COLORECTAL-CANCER
PROSTATE-CANCER
HEPATOCELLULAR-CARCINOMA
INHIBITS PROLIFERATION
PLUS SIMVASTATIN
UP-REGULATION
APOPTOSIS
METAANALYSIS
Adult
Aged
Aged, 80 and over
Antineoplastic Combined Chemotherapy Protocols
Carboplatin
Cisplatin
Disease-Free Survival
Double-Blind Method
Etoposide
Female
Humans
Lung Neoplasms
Male
Middle Aged
Pravastatin
Response Evaluation Criteria in Solid Tumors
Small Cell Lung Carcinoma
Survival Rate
1112 Oncology And Carcinogenesis
Oncology & Carcinogenesis
Publication Status: Published
Appears in Collections:Division of Surgery
Division of Cancer
Faculty of Medicine



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