Prognostic value of statins and beta-blockers in ovarian cancer

Despite improvement in cancer therapies, the prognosis of ovarian cancer remains quite poor with a relative 5-years survival of about 40% in European countries. Therefore, new treatment perspectives are required. One is to repurpose drugs to fight cancer. In this context, preclinical studies have shown that statins and -blockers could be promising. In order to analyse if these two classes of drugs can improve ovarian cancer survival, we performed population-based studies, clinical series and meta-analyses. All results were consistent and showed that statin users had a better survival. For β-blockers, analyses were more complex because β-blockers are prescribed for various pathologies that can be potentially serious and impact survival. However, our results show that the survival of β-blockers users is, at least, not worse than that of nonusers. Therefore, statins and β-blockers should be continued after a diagnosis of ovarian cancer.(MED - Sciences médicales) -- UCL, 202

Beta-blocker use and mortality following ovarian cancer diagnosis: a population-based study.

BACKGROUND: Preclinical studies suggest that β-blockers could exhibit anticancer properties in ovarian cancer. Similar effects have also been reported in observational studies, but their results remain inconsistent and could be impaired by methodological limitations. This study aimed to investigate whether β-blocker use is associated with improved survival in ovarian cancer patients at the Belgian population level. METHODS: We conducted a population-based study by linking data of the Belgian Cancer Registry with medical claims data of the health insurance companies for patients diagnosed with ovarian cancer between 2004 and 2014. Information on ovarian-cancer-specific deaths was retrieved from mortality records collected by regional governments. Use of β-blockers was modelled as a time-varying covariate in Cox regression models to calculate adjusted hazards ratios (HRs) and 95% confidence intervals (95%CIs) for the association between postdiagnostic β-blocker exposure and overall or cancer-specific survival (OS and CSS, respectively). Adjustments were made for age at diagnosis, year of diagnosis, comorbidities, cancer stage, and cancer treatments. RESULTS: In our population of 6197 patients, 2373 patients (38%) had at least one prescription of β-blockers in the 5 years following diagnosis. Postdiagnostic exposure to β-blockers was associated with a significant decrease in OS (adjusted HR, 1.21, 95%CI 1.12;1.30, p < 0.001) and CSS (adjusted HR, 1.17, 95%CI 1.07;1.29, p < 0.001). Moreover, this association remained similar in dose-response analyses, in subgroup analyses (including by β-blocker selectivity types), and in sensitivity analyses. CONCLUSION: In this large nationwide cohort of ovarian cancer patients, β-blocker users had reduced survival

Impact of metformin on gastric adenocarcinoma survival: A Belgian population based study

Background: Preclinical studies have shown anticancer activities of metformin in gastric cancer and a recent epidemiological study showed a decrease in recurrence and mortality of gastric cancer in metformin users. This study aimed to assess the impact of metformin on gastric cancer survival in diabetic patients at a Belgian population level. Methods: We conducted an observational, population-based study by linking data of the Belgian Cancer Registry with medical claims data coming from the health insurance companies for patients diagnosed with stage I to III gastric adenocarcinoma between 2006 and 2012. Information on gastric cancer-specific deaths was retrieved from mortality records collected by regional governments. Time-dependent Cox regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CI) for overall survival (OS) and cancer-specific mortality (CSS). Results: In our population of 371 patients, a reduction in all-cause mortality was observed in metformin users (adjusted HR=0.73, 95% CI: [0.52; 1.01], p=0.06) but not for cancer specific mortality (adjusted HR=0.86, 95% CI: [0.56; 1.33], p=0.50). Pre-diagnosis exposure to metformin was associated with a significant improvement in OS (adjusted HR=0.75, 95% CI: [0.57; 0.98], p=0.04) that was not significant for CSS (adjusted HR=0.89, 95% CI: [0.62; 1.28], p=0.52). Moreover, no dose-response relationship between metformin use and either all-cause or cancer-specific mortality was observed. Conclusion: In the first population based study of metformin use in gastric cancer adenocarcinoma patients with previous diabetes, our findings suggest that metformin use might improve overall mortality. However, no such association was found for cancer-specific survival. Additional studies in other populations are required

Statin use after diagnosis is associated with an increased survival in esophageal cancer patients: a Belgian population-based study

PURPOSE: Preclinical studies have shown that statins reduce proliferation in esophageal cancer. Three recent observational studies have shown encouraging results but suffered from limitations. This work aimed to assess at the Belgian population level whether statin usage was associated with a decreased mortality in esophageal cancer patients. METHODS: We conducted an observational, population-based study by linking data of the Belgian Cancer Registry (BCR) with medical claims data coming from health insurance companies and mortality records collected by regional governments for patients diagnosed with esophageal cancer between 2004 and 2014. Using time-dependent Cox regression models, hazard ratios (HRs) and 95% confidence intervals (CI) for overall and cancer-specific mortality were calculated. RESULTS: Of 6,238 patients with stage I-III esophageal cancer, post-diagnostic use of statins was found in 1,628 (26%) patients. Statins use after diagnosis was associated with a reduction in overall mortality (adjusted HR = 0.84, 95% CI [0.77; 0.92]) and cancer-specific mortality (adjusted HR = 0.87, 95% CI [0.78; 0.97]). Similar association were also seen for pre-diagnostic statin use in overall (adjusted HR = 0.83, 95% CI [0.76-0.91]) and cancer-specific analysis (adjusted HR = 0.86, 95% CI [0.77-0.96]). CONCLUSIONS: In this large cohort of Belgian patients with esophageal cancer, statins use after diagnosis was associated with a decreased mortality

Statin use is associated with improved survival in ovarian cancer: A retrospective population-based study

<div><p>Background</p><p>Preclinical in vitro and in vivo studies suggest that statins could exhibit anticancer properties in ovarian cancer. Similar effects have also been reported in observational studies but their results remain inconsistent and could be impaired by methodological limitations. This study aimed to investigate whether statin use is associated with improved survival in ovarian cancer patients at the Belgian population-level.</p><p>Methods</p><p>All patients with invasive epithelial ovarian cancer diagnosed between 2004 and 2012 were identified from the Belgian Cancer Registry. Vital statuses were obtained from the Crossroads Bank for Social Security and ovarian cancer-specific deaths were identified from death certificates provided by regional administrations. Information on cancer treatments and statin use were retrieved from health insurance databases. Statin use was modelled as a time-varying covariate in Cox regression models to calculate adjusted hazards ratios (HR) and 95% confidence intervals (95%CI) for the association between postdiagnostic exposure to statins and overall- or ovarian cancer-specific mortality within three years after diagnosis. Adjustments were made for age at diagnosis, year of diagnosis, comorbidities, cancer stage, and cancer treatments.</p><p>Results</p><p>A total of 5,416 patients with epithelial ovarian cancer met the inclusion criteria. Of these 1,255 (23%) had at least one statin prescription within three years after diagnosis. Postdiagnostic use of statins was associated with a reduced risk of overall mortality (adjusted HR = 0.81, 95%CI:0.72–0.90, p<0.001). In analyses by statin type, this association was only significant for simvastatin (adjusted HR = 0.86, 95%CI:0.74–0.99, p = 0.05) or rosuvastatin (adjusted HR = 0.71, 95%CI:0.55–0.92, p = 0.01). In subgroup analyses by statin prediagnostic use, the protective association for postdiagnostic statin use was only observed in patients who were also using statins before diagnosis (adjusted HR = 0.73, 95%CI:0.64–0.83, p<0.001). Similar results were observed for ovarian cancer-specific mortality.</p><p>Conclusion</p><p>In this large nation-wide cohort of ovarian cancer patients postdiagnostic use of statins was associated with improved survival.</p></div

Sensitivity analysis of association between statin use and overall mortality in patients with ovarian cancer.

<p>Sensitivity analysis of association between statin use and overall mortality in patients with ovarian cancer.</p

Association between statin use after diagnosis and overall mortality in patients with ovarian cancer.^*

<p>Association between statin use after diagnosis and overall mortality in patients with ovarian cancer.^{<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0189233#t002fn001" target="_blank">*</a>}</p

Flowchart of patients.

<p>NSSN stands for the National Social Security Number in Belgium.</p

Characteristics of ovarian cancer patients by statin use after diagnosis.

<p>Characteristics of ovarian cancer patients by statin use after diagnosis.</p