Subcutaneous Administration of Monoclonal Antibodies: Pharmacology, Delivery, Immunogenicity, and Learnings From Applications to Clinical Development.

Subcutaneous (s.c.) administration of monoclonal antibodies (mAbs) can reduce treatment burden for patients and healthcare systems compared with intravenous (i.

Dose Optimization in Oncology Drug Development: The Emerging Role of Pharmacogenomics, Pharmacokinetics, and Pharmacodynamics.

Drugs' safety and effectiveness are evaluated in randomized, dose-ranging trials in most therapeutic areas. However, this is only sometimes feasible in oncology, and dose-ranging studies are mainly limited to Phase 1 clinical trials. Moreover, although new treatment modalities (e.

Machine learning-guided covariate selection for time-to-event models developed from a small sample of real-world patients receiving bevacizumab treatment.

Therapeutic outcomes in patients with metastatic colorectal cancer (mCRC) receiving bevacizumab treatment are highly variable, and a reliable predictive factor is not available. Progression-free survival (PFS) and overall survival (OS) were recorded from an observational, prospective study after 5 years of follow-up, including 46 patients with mCRC receiving bevacizumab treatment. Three vascular endothelial growth factor (VEGF)-A and two intercellular adhesion molecule-1 genes polymorphisms, age, gender, weight, dosing scheme, and co-treatments were collected.

Lurbinectedin-induced thrombocytopenia: the role of body surface area.

Lurbinectedin is an alkylating agent approved for the second-line treatment of small cell lung cancer. Although initial studies showed no association between body surface area (BSA) and drug clearance, the recommended dose is 3.2 mg/m every 3 weeks.

Quantifying self-rated age.

Chronological age, in conjunction with population life tables, is widely used for estimating future life expectancy. The aims of this study are to estimate a subjective ageing indicator, namely self-rated age, and to evaluate its concurrent validity in comparison with other age indicators: subjective survival probabilities, subjective age, and biological age. We use data from the Wave 6 of the Survey of Health, Ageing and Retirement in Europe, Wave 12 of the Health and Retirement Study in the United States, and life tables from the Human Mortality Database.

The Urinary Microbiome and Bladder Cancer: Susceptibility and Immune Responsiveness.

Bladder cancer is a highly prevalent disease worldwide and is associated with a high mortality rate. Across all stages of bladder cancer, immunotherapy has now become the cornerstone of treatment. The commensal microbiome has become a major focus of research given its impact on numerous states of human health and disease.

In Reply.

This letter to the editor responds to Le Louedec et al. regarding the recently published article on the correlation between bevacizumab exposure and survival in patients with metastatic colorectal cancer.

Pharmacogenomics, Pharmacokinetics and Circulating Proteins as Biomarkers for Bevacizumab Treatment Optimization in Patients with Cancer: A Review.

Bevacizumab is a monoclonal antibody that targets VEGF-A and inhibits tumor angiogenesis. Bevacizumab is approved for the treatment of various cancer, including metastatic colorectal cancer (mCRC), ovarian cancer, lung cancer, and others. Thus, it is widely used in oncology, but contrary to other therapeutic classes, there is still a lack of validating predictive factors for treatment outcomes with these agents.

Pharmacogenetics in Model-Based Optimization of Bevacizumab Therapy for Metastatic Colorectal Cancer.

Vascular endothelial growth factor A (VEGF-A) and intercellular adhesion molecule 1 (ICAM-1) are significant regulators of angiogenesis, an important biological process involved in carcinogenesis. Bevacizumab, an anti-VEGF monoclonal antibody (MAB), is approved for the treatment of metastatic Colorectal cancer (mCRC), however clinical outcomes are highly variable. In the present study, we developed a pharmacokinetic (PK), a simplified quasi-steady state (QSS) and a pharmacokinetic/pharmacodynamic (PK/PD) model to identify potential sources of variability.

Correlation Between Bevacizumab Exposure and Survival in Patients with Metastatic Colorectal Cancer.

Background: Bevacizumab treatment is subject to large interpatient variability in efficacy, which may partly be explained by differences in complex bevacizumab pharmacokinetic characteristics that influence bevacizumab exposure. Exposure-response relationships have been identified for other monoclonal antibodies. We aimed to identify possible exposure-survival relationships in bevacizumab-treated patients with metastatic colorectal cancer (mCRC).

Do we need to adopt antifungal stewardship programmes?

Background: Although antimicrobial stewardship programmes are one of the highest priorities in healthcare systems and many articles have been published, few refer to the implementation of antifungal stewardship and highlight specific points on which efforts should be focused.

Objective: To assess the percentage of patients with confirmed candidaemia in whom de-escalation was conducted, and the economic impact of step-down or step-up antifungal therapy. Additionally, we attempted to estimate the potential increase in drug minimum inhibitory concentrations or to detect resistant strains of species.

and Gene Polymorphisms as Predictors of Clinical Outcome to First-Line Bevacizumab-Based Treatment in Metastatic Colorectal Cancer.

Bevacizumab is used to treat metastatic colorectal cancer (mCRC). However, there are still no available predictors of clinical outcomes. We investigated selected single nucleotide polymorphisms (SNPs) in the genes involved in VEGF-dependent and -independent angiogenesis pathways and other major intracellular signaling pathways involved in the pathogenesis of mCRC as an attempt to find predictors of clinical outcome.

Direct oral anticoagulant considerations in solid organ transplantation: A review.

For more than 60 years, warfarin was the only oral anticoagulation agent available for use in the United States. In many recent clinical trials, several direct oral anticoagulants (DOACs) demonstrated similar efficacy with an equal or superior safety profile, with some other notable benefits. The DOACs have lower inter- and intrapatient variability, much shorter half-lives, and less known drug-drug and drug-food interactions as compared to warfarin.

Drug Utilization Patterns and Costs of Erythropoiesis-Stimulating Agents in an Outpatient Setting in Greece.

Unlabelled: Anemia in the elderly is often related to a higher prevalence of chronic diseases such as chronic kidney failure, arthritis, and malignancy. Erythropoiesis-stimulating agents (ESAs) have been used for years to effectively treat anemia and when used appropriately can substantially improve the health status and quality of life of older adults. Following the 2008 recession in Greece, the government introduced ESA price control restrictions, but no prescribing restrictions, in an effort to reduce drug expenditure.

Personalizing chemotherapy dosing using pharmacological methods.

Purpose: Given the toxic nature and narrow therapeutic index of traditional chemotherapeutics, better methods of dose and therapy selection are critical. Pharmacological methods, including pharmacogenomics and pharmacokinetics, offer a practical method to enrich drug exposure, reduce toxicity, and improve quality of life for patients.

Methods: PubMed and key abstracts from the American Society of Clinical Oncology (ASCO) and American Association for Cancer Research (AACR) were searched until July 2015 for clinical data relating to pharmacogenomic- and/or pharmacokinetic-guided dosing of anticancer drugs.

Antibody-drug conjugates: a mini-review. The synopsis of two approved medicines.

Targeted drug delivery is a method of delivering bioactive compounds to a patient in a manner that increases the therapeutic index. The main goal of a targeted drug delivery system is to prolong, localize, target and have a protected drug interaction with the diseased tissue. Antibody-drug conjugates (ADC) represent an innovative therapeutic application that combines the unique properties of monoclonal antibodies with the potent cell killing activity of cytotoxic bioactive compounds.

Liposomal forms of anticancer agents beyond anthracyclines: present and future perspectives.

Liposomes are widely used as delivery systems of cytotoxic drugs. The encapsulation into liposomes improves pharmacological properties and as a result therapeutic index and outcomes. To date, liposomal vincristine and cytarabine are approved and marketed for intravenous and intrathecal administration, respectively.