Paolo Chiodini

Metabolic Syndrome and Risk of Cancer A systematic review and meta-analysis

OBJECTIVE Available evidence supports the emerging hypothesis that metabolic syndrome may be associated with the risk of some common cancers. We did a systematic review and meta-analysis to assess the association between metabolic syndrome and risk of cancer at different sites. RESEARCH DESIGN AND METHODS We conducted an electronic search for articles published through October 2011 without restrictions and by reviewing reference lists from retrieved articles. Every included study was to report risk estimates with 95% CIs for the association between metabolic syndrome and cancer. RESULTS We analyzed 116 datasets from 43 articles, including 38,940 cases of cancer. In cohort studies in men, the presence of metabolic syndrome was associated with liver (relative risk 1.43, P < 0.0001), colorectal (1.25, P < 0.001), and bladder cancer (1.10, P = 0.013). In cohort studies in women, the presence of metabolic syndrome was associated with endometrial (1.61, P = 0.001), pancreatic (1.58, P < 0.0001), breast postmenopausal (1.56, P = 0.017), rectal (1.52, P = 0.005), and colorectal (1.34, P = 0.006) cancers. Associations with metabolic syndrome were stronger in women than in men for pancreatic (P = 0.01) and rectal (P = 0.01) cancers. Associations were different between ethnic groups: we recorded stronger associations in Asia populations for liver cancer (P = 0.002), in European populations for colorectal cancer in women (P = 0.004), and in U.S. populations (whites) for prostate cancer (P = 0.001). CONCLUSIONS Metabolic syndrome is associated with increased risk of common cancers; for some cancers, the risk differs betweens sexes, populations, and definitions of metabolic syndrome.

Chemotherapy-induced neutropenia and treatment efficacy in advanced non-small-cell lung cancer: a pooled analysis of three randomised trials

BACKGROUND Chemotherapy is the standard treatment for advanced non-small-cell lung cancer, and myelosuppression is a common side-effect. We aimed to assess whether haematological toxic effects could be a biological measure of drug activity and a marker of efficacy. METHODS We analysed data for 1265 patients who received chemotherapy (vinorelbine, gemcitabine, gemcitabine and vinorelbine, cisplatin and vinorelbine, or cisplatin and gemcitabine) within three randomised trials. Primary landmark analyses were restricted to 436 patients who received all six planned chemotherapy cycles and who were alive 180 days after randomisation. Neutropenia was categorised on the basis of worst WHO grade during chemotherapy: absent (grade 0), mild (grade 1-2), or severe (grade 3-4). All statistical analyses were stratified by treatment allocation. Analyses were repeated in the out-of-landmark group (829 patients), stratifying by treatment allocation and number of chemotherapy cycles. The primary endpoint was overall survival. FINDINGS In the landmark group, hazard ratios of death were 0.65 (0.46-0.93) for patients with severe neutropenia and 0.74 (0.56-0.98) for those with mild neutropenia. Median survival after the landmark time of 180 days was 31.4 weeks (95% CI 25.7-39.6) for patients without neutropenia compared with 42.0 weeks (32.7-59.7) for patients with severe neutropenia, and with 43.7 weeks (36.6-66.0) for those with mild neutropenia (severe vs mild vs no neutropenia p=0.0118). Findings were much the same for the out-of-landmark group. INTERPRETATION Neutropenia during chemotherapy is associated with increased survival of patients with advanced non-small-cell lung cancer, and its absence might be a result of underdosing. Prospective trials are needed to assess whether drug dosing guided by the occurrence of toxic effects could improve efficacy of standard regimens.

Carboplatin- or Cisplatin-Based Chemotherapy in First-Line Treatment of Small-Cell Lung Cancer: The COCIS Meta-Analysis of Individual Patient Data

PURPOSE Since treatment efficacy of cisplatin- or carboplatin-based chemotherapy in the first-line treatment of small-cell lung cancer (SCLC) remains contentious, a meta-analysis of individual patient data was performed to compare the two treatments. PATIENTS AND METHODS A systematic review identified randomized trials comparing cisplatin with carboplatin in the first-line treatment of SCLC. Individual patient data were obtained from coordinating centers of all eligible trials. The primary end point was overall survival (OS). All statistical analyses were stratified by trial. Secondary end points were progression-free survival (PFS), objective response rate (ORR), and treatment toxicity. OS and PFS curves were compared by using the log-rank test. ORR was compared by using the Mantel-Haenszel test. RESULTS Four eligible trials with 663 patients (328 assigned to cisplatin and 335 to carboplatin) were included in the analysis. Median OS was 9.6 months for cisplatin and 9.4 months for carboplatin (hazard ratio [HR], 1.08; 95% CI, 0.92 to 1.27; P = .37). There was no evidence of treatment difference between the cisplatin and carboplatin arms according to sex, stage, performance status, or age. Median PFS was 5.5 and 5.3 months for cisplatin and carboplatin, respectively (HR, 1.10; 95% CI, 0.94 to 1.29; P = .25). ORR was 67.1% and 66.0%, respectively (relative risk, 0.98; 95% CI, 0.84 to 1.16; P = .83). Toxicity profile was significantly different for each of the arms: hematologic toxicity was higher with carboplatin, and nonhematologic toxicity was higher with cisplatin. CONCLUSION Our meta-analysis of individual patient data suggests no differences in efficacy between cisplatin and carboplatin in the first-line treatment of SCLC, but there are differences in the toxicity profile.

Fruit, vegetables, and olive oil and risk of coronary heart disease in Italian women: the EPICOR Study

BACKGROUND Many observational studies support the recommendation to eat sufficient amounts of fruit and vegetables as part of a healthy diet. OBJECTIVE The present study aimed to investigate the association between consumption of fruit, vegetables, and olive oil and the incidence of coronary heart disease (CHD) in 29,689 women enrolled between 1993 and 1998 in 5 European Prospective Investigation into Cancer and Nutrition (EPIC) cohorts in northern (Turin and Varese), central (Florence), and southern (Naples and Ragusa) Italy. DESIGN Baseline dietary, anthropometric, and lifestyle characteristics were collected. Major events of CHD (fatal and nonfatal myocardial infarction and coronary revascularization) were identified through a review of clinical records. Analyses were stratified by center and adjusted for hypertension, smoking, education, menopause, physical activity, anthropometric measures, nonalcohol energy, alcohol, total meat, vegetables in analyses for fruit, and fruit in analyses for vegetables. RESULTS During a mean follow-up of 7.85 y, 144 major CHD events were identified. A strong reduction in CHD risk among women in the highest quartile of consumption of leafy vegetables (hazard ratio: 0.54; 95% CI: 0.33, 0.90; P for trend = 0.03) and olive oil (hazard ratio: 0.56; 95% CI: 0.31, 0.99; P for trend = 0.04) was found. In contrast, no association emerged between fruit consumption and CHD risk. CONCLUSION An inverse association between increasing consumption of leafy vegetables and olive oil and CHD risk emerged in this large cohort of Italian women.

Dietary Glycemic Load and Index and Risk of Coronary Heart Disease in a Large Italian Cohort: The EPICOR Study

BACKGROUND Dietary glycemic load (GL) and glycemic index (GI) in relation to cardiovascular disease have been investigated in a few prospective studies with inconsistent results, particularly in men. The present EPICOR study investigated the association of GI and GL with coronary heart disease (CHD) in a large and heterogeneous cohort of Italian men and women originally recruited to the European Prospective Investigation into Cancer and Nutrition study. METHODS We studied 47 749 volunteers (15 171 men and 32 578 women) who completed a dietary questionnaire. Multivariate Cox proportional hazards modeling estimated adjusted relative risks (RRs) of CHD and 95% confidence intervals (CIs). RESULTS During a median of 7.9 years of follow-up, 463 CHD cases (158 women and 305 men) were identified. Women in the highest carbohydrate intake quartile had a significantly greater risk of CHD than did those in the lowest quartile (RR, 2.00; 95% CI, 1.16-3.43), with no association found in men (P = .04 for interaction). Increasing carbohydrate intake from high-GI foods was also significantly associated with greater risk of CHD in women (RR, 1.68; 95% CI, 1.02-2.75), whereas increasing the intake of low-GI carbohydrates was not. Women in the highest GL quartile had a significantly greater risk of CHD than did those in the lowest quartile (RR, 2.24; 95% CI, 1.26-3.98), with no significant association in men (P = .03 for interaction). CONCLUSION In this Italian cohort, high dietary GL and carbohydrate intake from high-GI foods increase the overall risk of CHD in women but not men.

Individual Patient Data Meta-Analysis of Docetaxel Administered Once Every 3 Weeks Compared With Once Every Week Second-Line Treatment of Advanced Non–Small-Cell Lung Cancer

PURPOSE Although several randomized trials have been performed comparing weekly docetaxel (wD) with standard docetaxel once every 3 weeks (3wD) as second-line treatment of advanced non-small-cell lung cancer (NSCLC), no single trial had sufficient power to detect clinically relevant differences in survival. METHODS We performed a meta-analysis based on individual patient data from all identified randomized trials comparing wD with 3wD as second-line treatment of advanced NSCLC. Baseline characteristics, treatment assigned, and outcome data were collected for each patient. The primary end point was overall survival. All statistical analyses were stratified by trial. RESULTS Five eligible trials were identified for a total of 865 patients: 433 patients had been assigned to 3wD, and 432 patients had been assigned to wD. Median age was 62 years (range, 26 to 80 years). Performance status was 0 in 23%, 1 in 58%, and 2 in 16% of patients; 91% of the patients had received previous platinum, and 14% had received previous paclitaxel. With 733 deaths recorded (85%), median survival was 27.4 weeks for patients treated with 3wD, and 26.1 weeks for patients treated with wD (P = .24, log-rank test). There was no significant heterogeneity among the five trials. No relevant differential effect was detected in subgroup analyses. Significantly less severe and febrile neutropenia was reported with wD (P < .00001 for both), whereas no significant differences were observed for anemia, thrombocytopenia, and nonhematologic toxicity. CONCLUSION wD shows similar efficacy compared with 3wD, and represents an alternative for second-line treatment of advanced NSCLC.

Efficacy of Insulin Analogs in Achieving the Hemoglobin A1c Target of <7% in Type 2 Diabetes: Meta-analysis of randomized controlled trials

OBJECTIVE Insulin analogs are increasingly used in patients with type 2 diabetes. We compared the effect of basal, biphasic, prandial, and basal-bolus insulin regimens with insulin analogs to reach the hemoglobin A1c (HbA1c) target of <7% in people with type 2 diabetes. RESEARCH DESIGN AND METHODS We conducted an electronic search for randomized controlled trials (RCTs) involving insulin analogs. RCTs were included if they lasted at least 12 weeks, reported the proportion of diabetic patients reaching the HbA1c target of <7% (primary outcome), and the number of patients in any arm was >30. RESULTS We found 16 RCTs, with 20 comparisons and 7,759 patients. A greater proportion of patients achieved the HbA1c goal of <7% with both biphasic (odds ratio 1.88 [95% CI 1.38–2.55]) and prandial (2.07 [1.16–3.69]) insulin compared with basal insulin; this was associated for biphasic insulin with greater hypoglycemia (event/patient/30 days, mean difference, 0.34 [range 0–0.69]) and weight gain in kg (1.0 kg [0.28–1.73]). Compared with biphasic insulin, the basal-bolus regimen was associated with a greater chance to reach the HbA1c goal (odds ratio 1.75 [95% CI 1.11–2.77]), with no greater hypoglycemia or weight gain. The effect of insulin analogs on long-term diabetes complications is still lacking. CONCLUSIONS A greater proportion of type 2 diabetic patients can achieve the HbA1c goal <7% with biphasic or prandial insulin compared with basal insulin; in absolute terms, the basal-bolus regimen was best for the attainment of the HbA1c goal.

A Priori–Defined Dietary Patterns Are Associated with Reduced Risk of Stroke in a Large Italian Cohort

Stroke is a major cause of death. Several foods and nutrients have been linked to stroke, but their effects may be best investigated considering the entire diet. In the present EPICOR study, we investigated the association between stroke and adherence to 4 a priori-defined dietary patterns: Healthy Eating Index 2005 (HEI-2005), Dietary Approaches to Stop Hypertension (DASH), Greek Mediterranean Index, and Italian Mediterranean Index. We followed 40,681 volunteers and estimated the HR and 95%CI for stroke according to dietary pattern by using multivariate Cox models with adjustment for risk factors. During a mean follow-up of 7.9 y, 178 stroke cases were diagnosed (100 ischemic, 47 hemorrhagic). Scores of 3 dietary patterns (not HEI) were inversely associated with risk of all types of stroke, with the strongest association for the Italian Index [HR = 0.47 (95%CI = 0.30-0.75); third vs. first tertile]. All patterns were significantly inversely associated with ischemic stroke except the Greek Index, with the strongest association for the Italian Index [HR = 0.37 (95%CI = 0.19-0.70); third vs. first tertile]. Only the Italian Index tended to be inversely associated with hemorrhagic stroke [HR = 0.51 (95%CI = 0.22-1.20); P = 0.07)]. These epidemiological findings suggest that adherence to any one dietary pattern investigated would protect against at least one type of stroke. For our Italian population, a diet with a high score on the Italian Index was associated with the greatest risk reduction, probably because it was conceived to capture healthy eating in the context of foods typically available in Italy.

Proportion of patients at HbA1c target <7% with eight classes of antidiabetic drugs in type 2 diabetes: systematic review of 218 randomized controlled trials with 78 945 patients

Aim: We assessed the efficacy of eight classes of diabetes medications used in current clinical practice [metformin, sulphonylureas, α‐glucosidase inhibitors, thiazolidinediones, glinides, dipeptidyl peptidase‐4 inhibitors, glucagon‐like peptide‐1 (GLP‐1) analogues and insulin analogues] to reach the HbA1c target <7% in type 2 diabetes.

Dipeptidyl peptidase-4 inhibitors and HbA1c target of <7% in type 2 diabetes: meta-analysis of randomized controlled trials

Aim: We assessed the efficacy of dipeptidyl peptidase‐4 (DPP‐4) inhibitors vildagliptin, sitagliptin, saxagliptin and alogliptin to reach the haemoglobin HbA1c target of <7% in people with type 2 diabetes.