Cost-effectiveness analysis of ribociclib plus fulvestrant for hormone receptor-positive/human EGF receptor 2-negative breast cancer.

Aim: To evaluate the cost-effectiveness of ribociclib plus fulvestrant versus fulvestrant in hormone receptor-positive/human EGF receptor 2-negative advanced breast cancer. Materials & methods: A three-state Markov model was developed to evaluate the costs and effectiveness over 10 years. Direct costs and utility values were obtained from previously published studies. We calculated incremental cost-effectiveness ratio to evaluate the cost-effectiveness at a willingness-to-pay threshold of $150,000 per additional quality-adjusted life year. Results: The incremental cost-effectiveness ratio was $1,073,526 per quality-adjusted life year of ribociclib plus fulvestrant versus fulvestrant. Conclusions: Ribociclib plus fulvestrant is not cost-effective versus fulvestrant in the treatment of advanced hormone receptor-positive/human EGF receptor 2-negative breast cancer. When ribociclib is at 10% of the full price, ribociclib plus fulvestrant could be cost-effective.

Developing an isotope dilution UHPLC-MS/MS method to quantify linezolid in human plasma: application to therapeutic drug monitoring.

Aim: To optimize clinical efficacy and reduce the drug-exposure-related toxicity of linezolid, whose concentrations show wide inter-variabilities, a simple and reliable quantitative assay for therapeutic drug monitoring is necessary. Results: A UHPLC-MS/MS assay has been established for determination of linezolid in human plasma and fully validated according to the US FDA guidelines. After a simple, isotope-dilluted precipitation with methanol, the analytes were separated by a straightforward isocratic mode and the MS/MS was conducted under the ESI+ mode fitted with SRM. The calibration curves proved acceptable linearity in the range of 0.1-30.0 µg/ml. Conclusion: The present assay is currently used in routine clinical practice, being applied to therapeutic drug monitoring and helps to optimize individual dosing regimens and manage adverse effects in ICU patients.

Association of glucose-lowering medications with cardiovascular outcomes: an umbrella review and evidence map.

BACKGROUND: Considering the global burden of diabetes and associated cardiovascular disease, an urgent need exists for the best treatment, which should be based on the best available evidence. We examined the association between glucose-lowering medications and a broad range of cardiovascular outcomes, and assessed the strength of evidence for these associations. METHODS: For this umbrella review we searched PubMed, Embase, and the Cochrane Library to identify systematic reviews and meta-analyses of randomised controlled trials examining the cardiovascular safety of glucose-lowering medications. Cardiovascular outcomes examined included major adverse cardiovascular events, cardiovascular death, myocardial infarction, stroke, heart failure, unstable angina, and atrial fibrillation. For each meta-analysis, we estimated the relative risk (RR) and 95% CI. We also created an evidence map showing the plausible benefits or harms of each intervention and the certainty of the evidence. FINDINGS: We examined 232 meta-analyses evaluating ten classes of diabetes drugs. We identified six risk and 38 protective associations showing a high strength of evidence. Six associations increased the risk of cardiovascular disease, including glimepiride (stroke [RR 2·01; 95% CI 1·02-3·98]), rosiglitazone (myocardial infarction [1·28; 1·02-1·62] and heart failure [1·72, 1·31-2·27]), and pioglitazone (heart failure [1·40; 1·16-1·69]). 38 associations decreased the risk of cardiovascular disease, including glucagon-like peptide-1 receptor agonists as a class (major adverse cardiovascular events [RR 0·88; 95% CI 0·84-0·92], death from cardiovascular disease [0·87; 0·81-0·94], myocardial infarction [0·92; 0·86-0·99], stroke [0·84; 0·77-0·93], and heart failure [0·90; 0·83-0·99]), albiglutide (major adverse cardiovascular events [0·81; 0·68-0·96], myocardial infarction [0·77; 0·64-0·92], and heart failure [0·71; 0·55-0·93]), dulaglutide (stroke [0·78; 0·64-0·96]), exenatide (major adverse cardiovascular events [0·91; 0·83-1·00]), liraglutide (major adverse cardiovascular events [0·86; 0·77-0·96]), semaglutide (major adverse cardiovascular events [0·76; 0·62-0·92] and stroke [0·67; 0·45-1·00]), sodium-glucose co-transporter-2 inhibitors as a class (major adverse cardiovascular events [0·87; 0·82-0·93], death from cardiovascular disease [0·82; 0·75-0·90], myocardial infarction [0·86; 0·78-0·94], and heart failure [0·68; 0·63-0·73]), canagliflozin (major adverse cardiovascular events [0·84; 0·75-0·93], death from cardiovascular disease [0·82; 0·71-0·96], and heart failure [0·65; 0·54-0·78]), dapagliflozin (heart failure [0·70; 0·60-0·82]), empagliflozin (major adverse cardiovascular events [0·85; 0·77-0·94], death from cardiovascular disease [0·62; 0·50-0·78], and heart failure [0·64; 0·53-0·77]), and pioglitazone (major adverse cardiovascular events [0·84; 0·74-0·96], myocardial infarction [0·80; 0·67-0·95], and stroke [0·79; 0·65-0·95]). INTERPRETATION: We found varied levels of evidence for the associations between diabetes drugs and cardiovascular outcomes; some drugs raised the risk of cardiovascular disease, whereas others showed benefit. FUNDING: None.

Risk of adverse events in lymphoma patients treated with brentuximab vedotin: a systematic review and meta-analysis.

Objectives: To assess the risk of adverse events (AEs) associated with brentuximab vedotin in lymphoma patients.Methods: Articles were retrieved from PubMed, Cochrane, and Clinicaltrials Databases to identify randomized controlled trials (RCTs) comparing brentuximab vedotin with non-brentuximab vedotin in lymphoma patients.Results: A total of 2225 patients from 4 RCTs were included. Compared with the non-brentuximab vedotin group, the brentuximab vedotin group significantly increased the risk of all-grade AEs (RR 1.05, 95% CI: 1.00-1.10), and high-grade AEs (risk ratio [RR] 1.27, 95% confidence intervals [CI]: 1.01-1.58). The brentuximab vedotin group significantly increased the risk of all-grade peripheral sensory neuropathy (RR 2.29, 95% CI: 1.23-4.26), pyrexia (RR 1.23, 95% CI: 1.05-1.44), nausea (RR 1.51, 95% CI: 1.05-2.18), vomiting (RR 1.54, 95% CI: 1.08-2.19), diarrhea (RR 1.69, 95% CI: 1.44-1.98), and alopecia (RR 1.18, 95% CI: 1.00-1.39), respectively. The brentuximab vedotin group significantly increased the risk of high-grade sensory neuropathy (RR 4.79, 95% CI: 1.46-15.75), neutropenia (RR 1.48, 95% CI: 1.01-2.18), nausea (RR 2.65, 95% CI: 1.37-5.12), vomiting (RR 2.2, 95% CI: 1.17-4.12), and diarrhea (RR 1.85, 95% CI: 1.21-2.85).Conclusion: Brentuximab vedotin increased the risk of certain AEs in lymphoma patients.

Amphiphilic Copolymeric Micelles for Doxorubicin and Curcumin Co-Delivery to Reverse Multidrug Resistance in Breast Cancer.

Development of multidrug resistance against chemotherapeutic drugs is one of the major obstacles to successful cancer therapy in the clinic. Thus far, amphiphilic polymeric micelles and chemosensitizers have been used to overcome multidrug resistance in cancer. The goals of this study were to prepare poly(ethylene glycol)-bock-poly(lactide) (PEG(2k)-PLA(5k)) micelles for co-delivery of the chemotherapeutic drug doxorubicin (DOX) with a chemosensitizer curcumin (CUR), investigate the potential of the dual drug-loaded micelles ((DOX+CUR)-Micelles) to reverse multidrug resistance, and explore the underlying mechanisms. (DOX + CUR)-Micelles were prepared using an emulsion solvent evaporation method. The cellular uptake, drug efflux, down-regulation of P-glycoprotein expression and inhibition of ATP activity of (DOX+ CUR)-Micelles were studied in drug-resistant MCF-7/ADR cells. In vitro analyses demonstrated that (DOX + CUR)-Micelles were superior to free DOX, free drug combination (DOX + CUR), and DOX-loaded micelles in inhibiting proliferation of MCF-7/ADR cells. This effect of (DOX + CUR)-Micelles was partially attributable to their highest cellular uptake, lowest efflux rate of DOX, and strongest effects on down-regulation of P-glycoprotein and inhibition of ATP activity. Additionally, (DOX+CUR)-Micelles showed increased tumor accumulation and strong inhibitory effect on tumor growth in the xenograft model of drug-resistant MCF-7/ADR cells compared to that of other drug formulations. These results indicate that (DOX + CUR)-Micelles display potential for application in the therapy of drug-resistant breast carcinoma.

Quercetin and doxorubicin co-encapsulated biotin receptor-targeting nanoparticles for minimizing drug resistance in breast cancer.

The combination of a chemotherapeutic drug with a chemosensitizer has emerged as a promising strategy for cancers showing multidrug resistance (MDR). Herein we describe the simultaneous targeted delivery of two drugs to tumor cells by using biotin-decorated poly(ethylene glycol)-b-poly(ε-caprolactone) nanoparticles encapsulating the chemotherapeutic drug doxorubicin and the chemosensitizer quercetin (BNDQ). Next, the potential ability of BNDQ to reverse MDR in vitro and in vivo was investigated. Studies demonstrated that BNDQ was more effectively taken up with less efflux by doxorubicin-resistant MCF-7 breast cancer cells (MCF-7/ADR cells) than by the cells treated with the free drugs, single-drug-loaded nanoparticles, or non-biotin-decorated nanoparticles. BNDQ exhibited clear inhibition of both the activity and expression of P-glycoprotein in MCF-7/ADR cells. More importantly, it caused a significant reduction in doxorubicin resistance in MCF-7/ADR breast cancer cells both in vitro and in vivo, among all the groups. Overall, this study suggests that BNDQ has a potential role in the treatment of drug-resistant breast cancer.