Use of Statins and Outcome of BCG Treatment for Bladder Cancer

Hoffmann, Paul; Roumeguère, Thierry; Schulman, Claude; Velthoven, Roland Van

doi:10.1056/nejmc062714

Cited by 66 publications

(48 citation statements)

References 5 publications

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“…Based on these comprehensive findings, many studies have investigated antitumor activity of statins with or without cytotoxic chemotherapeutic agents for overcoming drug resistance or potentiating cytotoxicity. Indeed, statins have been found to have anticancer activity in various cell types, including colorectal [8], bladder [9], prostate [10], and multiple myeloma [11], though it should be validated in clinical trials.…”

Section: Introductionmentioning

confidence: 99%

Simvastatin enhances irinotecan-induced apoptosis in human non-small cell lung cancer cells by inhibition of proteasome activity

et al. 2010

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Simvastatin, a potent inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA) is known to stimulate apoptotic cell death and induce cell cycle arrest through inhibition of proteasome. The purpose of this study is to investigate whether simvastatin would be synergistic with irinotecan against human non-small cell lung cancer (NSCLC) cells. Antitumor effect was measured by growth inhibition of cells and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The cytotoxic interaction between irinotecan and simvastatin was assessed using the combination index. Effects on cell cycle distribution and apoptosis were determined by flow cytometry and DNA fragmentation. Proteasome activity was measured by ELISA quantification of 20S proteasome. NF-κB activation was determined using TransAM™ NF-κB p65 Transcription Factor Assay Kit. IκB-α was measured by immunoblot. A combination of irinotecan with simvastatin showed significantly enhanced cell growth inhibition compared with irinotecan alone, which resulted in a synergistic cytotoxicity. Irinotecan and simvastatin combination treatment of A549 and H460 cells increased G(1) phase arrest, which was associated with up-regulation of p21(WAF1/CIP) and p53 compared with irinotecan alone. In addition, simvastatin combination treatment increased irinotecan-related apoptosis as determined by fluorescence microscopy and flow cytometric analysis. We also found that combination therapy showed superior proteasome inhibitory activity leading to effectively suppress NF-κB transcription factor activation. Consistently, this effect was associated with up-regulation of IκB-α. These findings suggest that simvastatin enhances irinotecan-induced apoptosis in human NSCLC cells through inhibition of proteasome activity.

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Section: Introductionmentioning

confidence: 99%

Simvastatin enhances irinotecan-induced apoptosis in human non-small cell lung cancer cells by inhibition of proteasome activity

et al. 2010

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“…Although these drugs have a potential negative effect on the immune response to BCG treatment, neither had an effect on the clinical efficacy of BCG therapy in multiple clinical studies. [27][28][29][30][31][32] Other relative contraindications are prosthetic valves or orthopaedic hardware. However, a large phase II study with BCG combination therapy reported no infectious complications in the absence of prophylactic anti biotics, suggesting this population represents a lowrisk setting.…”

Section: Practical Issues Of Bcg Administrationmentioning

confidence: 99%

Consensus statement on best practice management regarding the use of intravesical immunotherapy with BCG for bladder cancer

et al. 2015

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| Multiple clinical trials have demonstrated that intravesical Bacillus Calmette-Guérin (BCG) treatment reduces recurrences and progression in patients with non-muscle-invasive bladder cancer (NMIBC). However, although BCG has been in use for almost 40 years, this agent is often underutilized and practice patterns of administration vary. This neglect is most likely caused by uncertainties about the optimal use of BCG, including unawareness of optimal treatment schedules and about patient populations that most benefit from BCG treatment. To address this deficit, a focus group of specialized urologic oncologists (urologists, medical oncologists and radiation oncologists) reviewed the current guidelines and clinical evidence, discussed their experiences and formed a consensus regarding the optimal use of BCG in the management of patients with NIMBC. The experts concluded that continuing therapy with 3-week BCG maintenance is superior to induction treatment only and is the single most important factor in improving outcomes in patients with NMIBC. They also concluded that a reliable alternative to radical cystectomy in truly BCG-refractory disease remains the subject of clinical trials. In addition, definitions for common terms of BCG failure, such as BCG-refractory and BCG-intolerant, have been formulated.

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“…In a 2006 observational study, Hoffmann et al [21] initially reported adverse clinical outcomes with statin use in a cohort of 84 patients who received BCG for NMIBC. They reported that patients concomitantly using statins were more likely to undergo radical cystectomy [odds ratio (OR) = 4.5, p = 0.01] and experience tumor progression (OR = 4.9, p = 0.004), suggesting that discontinuation of statins during BCG therapy may improve outcomes.…”

Section: Statinsmentioning

confidence: 99%

“…Aside from their cholesterol-lower mechanism via inhibition of 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase, statins have also independently demonstrated immunomodulatory properties by inhibiting T H 1-cell activation and development while promoting anti-inflammatory T H 2 cytokine secretion [14,15]. Concomitant use of anti-inflammatory agents or fibrin clot inhibitors with intravesical BCG has generated conflicting reports regarding the resultant efficacy of BCG in treating NMIBC, owing to the hypothesized interference with BCG's fibronectin-mediated uptake [16][17][18] and subsequent immunomodulatory effects [19][20][21][22][23]. In the present study, we sought to evaluate whether the use of anti-inflammatory agents affects oncologic outcomes in patients receiving intravesical BCG therapy for high-grade (HG) NMIBC.…”

Section: Introductionmentioning

confidence: 99%

Anti-inflammatory use may not negatively impact oncologic outcomes following intravesical BCG for high-grade non-muscle-invasive bladder cancer

et al. 2016

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Use of Statins and Outcome of BCG Treatment for Bladder Cancer

Cited by 66 publications

References 5 publications

Simvastatin enhances irinotecan-induced apoptosis in human non-small cell lung cancer cells by inhibition of proteasome activity

Simvastatin enhances irinotecan-induced apoptosis in human non-small cell lung cancer cells by inhibition of proteasome activity

Consensus statement on best practice management regarding the use of intravesical immunotherapy with BCG for bladder cancer

Anti-inflammatory use may not negatively impact oncologic outcomes following intravesical BCG for high-grade non-muscle-invasive bladder cancer

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