Major adverse cardiovascular events associated with VEGF-targeted anticancer tyrosine kinase inhibitors: a real-life study and proposed algorithm for proactive management.

BACKGROUND: Vascular endothelial growth factor receptor (VEGFR)-targeted tyrosine kinase inhibitors (TKIs) are widely used in cancer treatment and burdened by cardiovascular toxicity. The majority of data come from clinical trials, thus in selected populations. The aim of our study is to evaluate the cardiotoxicity profile of VEGFR-targeted TKIs and the impact of cardiovascular risk factors in a real-life population. PATIENTS AND METHODS: In this cohort, population-based study, patients treated with VEGFR-targeted TKIs, bevacizumab and trastuzumab between 2009 and 2014 were analyzed. A multi-source strategy for data retrieval through hospital, pharmaceutical and administrative databases of the Lombardy region, Italy, has been adopted. The primary endpoint was to determine the incidence and type of major adverse cardiovascular events (MACEs) along with their temporal trend. The secondary endpoint was to define the impact of cardiovascular risk factors in the occurrence of MACEs. RESULTS: A total of 829 patients were treated with VEGFR-targeted TKIs. Eighty-one MACEs occurred in the first year of follow-up [crude cumulative incidence (CCI): 9.79%] mainly consisting of arterial thrombotic events (ATEs, 31 events, CCI: 3.99%), followed by rhythm disorders (22 events, CCI: 2.66%), pulmonary embolisms and heart failures (13 events each, CCI: 1.57%). While the incidence of most MACEs showed a plateau after 6 months, ATEs kept increasing along the year of follow-up. Hypertension and dyslipidemia were associated with an increase in risk of ATEs [relative risk difference (RRD) +209.8% and +156.2%, respectively], while the presence of previous MACEs correlated with a higher risk of all MACEs in multivariate analysis (RRD 151.1%, 95% confidence interval 53.6% to 310.3%, P < 0.001). CONCLUSIONS: MACEs occur in a clinically significant proportion of patients treated with VEGFR-targeted TKIs, with ATEs being predominant, mainly associated with hypertension and dyslipidemia. A clinical algorithm for effective proactive management of these patients is warranted.

Diabetes mellitus and the risk of prostate cancer in Italy.

OBJECTIVE: We investigated the relation between diabetes and the risk of prostate cancer, as epidemiological results are controversial. METHODS: A hospital-based case-control study was conducted in Italy between 1991 and 2002. Cases were 1294 men, aged <75 years, with incident histologically confirmed prostate cancer, and controls were 1451 men, aged <75 years, admitted to hospital for acute non-neoplastic diseases. Odds ratios (OR) and the corresponding 95% confidence intervals (CI) were estimated using unconditional multiple logistic regression models. RESULTS: No material association between diabetes and prostate cancer was observed, with a multivariate OR of 1.02 (95%CI 0.75-1.40). Prostate cancer was not related to time since diagnosis of diabetes (OR 0.82 and 0.97 for <5 and >/=15 years since diagnosis respectively). The OR were respectively 1.63 (95%CI 0.70-3.81) and 0.96 (95%CI 0.68-1.34) in men diagnosed with diabetes at age <45 or >/=45 years. The risk estimates were similar across strata of age at interview, body mass index and, among cases, of Gleason score. CONCLUSIONS: This study shows no material association between diabetes and prostate cancer risk.

Fiber intake and risk of nonfatal acute myocardial infarction.

OBJECTIVE: To investigate the association between fiber intake and risk of acute myocardial infarction (AMI), also according to type and source of fiber, in a Mediterranean country. DESIGN: Hospital-based case-control study. SETTING: Northern Italy. SUBJECTS: A total of 507 cases of first nonfatal AMI and 478 controls in hospital for acute conditions. INTERVENTIONS: Subjects were interviewed with a questionnaire that included a validated food frequency section. Odds ratios (OR) were obtained using multiple logistic regression, and adjusted for several recognized risk factors for AMI. Fiber was measured as non-starch polysaccharides. RESULTS: Compared with the lowest one, the OR in the highest tertile was 0.72 for total fiber, 0.64 for soluble fiber, 0.77 for total insoluble fiber, 0.71 for cellulose, 0.81 for insoluble non-cellulosic polysaccharides, 0.82 for vegetable fiber, 0.64 for fruit fiber and 1.11 for cereal fiber, and the estimates were statistically significant for soluble and fruit fiber. When further adjusted for beta-carotene, vitamin C and vitamin E intake, the fruit fiber still showed the strongest inverse relation, although the association was no longer significant. The protective effect of fiber was more marked in, or restricted to, subjects with other AMI risk factors, such as smokers, diabetics and hypertensives. CONCLUSIONS: Though an inverse association between fiber intake and AMI risk appears established, the causality of this association is still open to debate. In this population, cereal fiber derives chiefly from refined grains, and this may explain the lack of protection by this type of fiber.

Does coffee protect against hepatocellular carcinoma?

We analysed the relation between coffee consumption and hepatocellular carcinoma in two case-control studies conducted between 1984 and 1998 in Italy and Greece, including 834 cases and 1912 controls. Compared to non coffee drinkers, the multivariate odds ratio was 0.7 for drinkers of three or more cups per day.

Cancer of the larynx in non-smoking alcohol drinkers and in non-drinking tobacco smokers.

The separate effect of alcohol and tobacco on laryngeal cancer was analysed in two case-control studies from Italy and Switzerland, comprising 40 non-smoking and 68 non-drinking cases, and 160 non-smoking and 161 non-drinking controls. The multivariate odds ratio was 2.46 for heavy drinkers non-smokers, and 9.38 for current smokers non-drinkers.

Alcohol, smoking, coffee and risk of non-fatal acute myocardial infarction in Italy.

OBJECTIVES: To assess the relation between cigarette smoking, alcohol, coffee, decaffeinated coffee and tea consumption, and the risk of non-fatal acute myocardial infarction (AMI). DESIGN AND SETTING: Hospital-based case-control study conducted in 1995-1999 in Milan, Italy. PATIENTS: 507 cases with a first episode of non-fatal AMI, and 478 controls admitted to hospital for acute diseases. METHODS: Information was collected by interviewer-administered questionnaires. Odds ratios (OR) and 95% confidence intervals (CI) were calculated by multiple logistic regression. RESULTS: Compared to alcohol non-drinkers the OR was 0.6 (95% CI: 0.4-0.9) in drinkers, and 0.5 in drinkers of > 3 drinks/day. The OR for > 1 drink/day of wine was 0.5, and those for beer, amari, grappa and spirits ranged between 0.4 and 0.6. Compared to never smokers, the OR was 2.2 (95% CI: 1.5-3.1) among current smokers, and 4.6 among current smokers of > or = 25 cigarettes/day. The risk was similar to that of never smokers > or = 5 years after cessation (OR: 1.1 after 5-9 years, 0.7 after > or = 10 years). The OR was 2.3 for low tar cigarettes and 2.0 for high tar ones. The OR for coffee intake (expresso and mocha) was around unity up to 3 cups/ day, but rose to 1.9 (95% CI: 1.1-3.3) for > or = 6 cups/ day. Moderate decaffeinated coffee and tea intake was not associated with AMI risk. Compared to non-smokers drinking < or = 3 cups of coffee/day, the OR was 1.6 among non-smokers drinking > 3 cups of coffee/ day and 3.3 (95% CI: 2.1-5.0) among current smokers drinking < or = 3 cups of coffee/day. Compared to alcohol drinkers with a coffee intake of < or = 3 cups/ day, alcohol non-drinkers with higher coffee intake had an OR of 2.2, and compared to non-smokers alcohol drinkers, the OR was 3.3 in current smokers alcohol non-drinkers. CONCLUSIONS: In this Italian population alcohol intake was inversely associated to AMI risk, while smoking and heavy (but not moderate) coffee drinking increased the risk.