Plasma levels of polychlorinated biphenyls (PCB) and the risk of soft tissue sarcoma

Background::Soft tissue sarcoma (STS) is a heterogeneous group of rare neoplasms whose aetiology is largely unknown. Dioxin and dioxin-like compounds, including 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) and polychlorinated biphenyls (PCBs), are potential risk factors for STS.Objectives:To investigate the relation of 17 PCBs congeners, assessed in human plasma, with STS risk.Methods:We conducted a case-control study in Italy, including 52 STS cases and 99 hospital-based controls. Selected PCB were extracted by high-performance liquid chromatography (HPLC) and measured with gas chromatography-mass spectrometry (GC-MS). Odds ratios (OR), and the corresponding 95% confidence intervals (CI), were estimated through multivariate logistic regression models.Results:The most frequently detected PCB congeners were 138, 170, 180 and 149 (detected in 40-77% of controls). The OR for the sum of all 17 PCB congeners was 1.20 (95% CI 0.50-2.92). In categorical analysis no consistent association was found for individual congeners and for groups based on Wolff’s classification or the degree of chlorination. For continuous estimates, borderline positive associations emerged for Wolff’s groups 2A (OR 1.23, 95% CI 0.97-1.55), 2B (OR 1.34, 95% CI 1.00-1.77, and 3 (OR 1.19, 95% CI 0.96-1.49), for moderately (OR 1.20, 95% CI 0.96-1.51) and highly (OR 1.18, 95% CI 0.99-1.41) chlorinated PCBs, and for congeners 170 (OR 1.26, 95% CI 0.98-1.63), 180 (OR 1.26, 95% CI 0.97-1.64) and 138 (OR 1.45, 95% CI 1.02-2.04).Discussion:Most associations between PCBs and STS risk were not significant, but, given the limited sample size, we cannot exclude moderate associations.Key words: Soft tissue sarcoma, polychlorinated biphenyls, epidemiology, environmental risk factors, chemical contaminants, case-control study     

New drugs in early-stage clinical trials for allergic rhinitis

Introduction: Allergic rhinitis (AR) is the most common allergic disease, and it has a relevant impact on the quality of life of the patient. Treatment of AR includes a combination of strategies of proven efficacy and effectiveness; however, a relevant proportion of patients remain uncontrolled.

Areas covered: This review article summarizes emerging therapeutic approaches to AR; these approaches include nasal sprays, oral drugs, alternative allergen immunotherapy administration routes, and biologic agents.

Expert opinion: The agents discussed require further clinical trials to prove their efficacy in the treatment of AR. Some of these agents, in particular, allergen immunotherapies and biologics, have the potential to form crucial precision medicine approaches to AR. Those that prove their efficacy in clinical trials must also be evaluated from a pharmacoeconomic perspective, possibly in real-life studies; this will define which therapeutic strategies achieve the most convenient and cost-effective ratio, thus yielding a novel opportunity for the most severe and previously treatment-resistant allergic patients.     

Real‐world experience with decitabine as a first‐line treatment in 306 elderly acute myeloid leukaemia patients unfit for intensive chemotherapy

Despite widespread use of decitabine to treat acute myeloid leukaemia (AML), data on its effectiveness and safety in the real‐world setting are scanty. Thus, to analyze the performance of decitabine in clinical practice, we pooled together patient‐level data of three multicentric observational studies conducted since 2013 throughout Italy, including 306 elderly AML patients (median age 75 years), unfit for intensive chemotherapy, treated with first‐line decitabine therapy at the registered schedule of 20 mg/m²/iv daily for 5 days every 4 weeks. Overall response rate (ORR), overall survival (OS) curves, and multivariate hazard ratios (HRs) of all‐cause mortality were computed. Overall, 1940 cycles of therapy were administered (median, 5 cycles/patient). A total of 148 subjects were responders and, therefore, ORR was 48.4%. Seventy‐one patients (23.2%) had complete remission, 32 (10.5%) had partial remission, and 45 (14.7%) had haematologic improvement. Median OS was 11.6 months for patients with favourable‐intermediate cytogenetic risk and 7.9 months for those with adverse cytogenetic risk. Median relapse‐free survival after CR was 10.9 months (95% confidence interval [CI]: 8.7‐16.0). In multivariate analysis, mortality was higher in patients with adverse cytogenetic risk (HR=1.58; 95% CI: 1.13‐2.21) and increased continuously with white blood cell (WBC) count (HR=1.12; 95% CI: 1.06‐1.18). A total of 183 infectious adverse events occurred in 136 patients mainly (>90%) within the first five cycles of therapy. This pooled analysis of clinical care studies confirmed, outside of clinical trials, the effectiveness of decitabine as first‐line therapy for AML in elderly patients unfit for intensive chemotherapy. An adverse cytogenetic profile and a higher WBC count at diagnosis were, in this real life setting, unfavourable predictors of survival.