Circulating tumor DNA-guided treatment decision in metastatic castration-resistant prostate cancer patients: a cost-effectiveness analysis.

Background: The androgen receptor pathway inhibitors (ARPI), abiraterone acetate and enzalutamide, are commonly used in first-line treatment of patients with metastatic castration-resistant prostate cancer (mCRPC). However, early resistance to ARPI treatment occurs frequently. Traditionally, the response is evaluated 3-6 months after the start of treatment.

Dose selection of novel anticancer drugs: exposing the gap between selected and required doses.

Historically, dose selection of anticancer drugs has mainly been based on establishing the maximum tolerated dose in phase 1 clinical trials with a traditional 3 plus 3 design. In the era of targeted therapies and immune-modulating agents, this approach does not necessarily lead to selection of the most favourable dose. This strategy can introduce potentially avoidable toxicity or inconvenience for patients.

A Prospective Randomised Trial to Determine the Effect of a Reduced Versus Standard Dose of Enzalutamide on Side Effects in Frail Patients with Prostate Cancer.

Background And Objective: Enzalutamide is a potent androgen receptor signalling inhibitor, effectively used for the treatment of different stages of prostate cancer. Side effects occur frequently at the registered dose, whilst a lower dose might be equally effective. Therefore, the aim of this study is to determine the effect of a reduced dose of enzalutamide on side effects in frail patients with prostate cancer.

Prognostic Value of Nivolumab Clearance in Non-Small Cell Lung Cancer Patients for Survival Early in Treatment.

Introduction: Immune checkpoint inhibitors improved survival of advanced stage non-small cell lung cancer patients, but the overall response rate remains low. A biomarker that identifies non-responders would be helpful to allow treatment decisions. Clearance of immune checkpoint inhibitors is related to treatment response, but its prognostic potential early in treatment remains unknown.

Clinical Pharmacokinetics and Pharmacodynamics of the Next Generation Androgen Receptor Inhibitor-Darolutamide.

Darolutamide is a next-generation androgen receptor signaling inhibitor (ARSI) currently approved for the treatment of nonmetastatic castration-resistant prostate cancer (nmCRPC) and metastatic hormone sensitive prostate cancer (mHSPC). Studies suggest that darolutamide also has the potential to be used to treat other stages of prostate cancer (PC), suggesting that its indications will broaden in the near future. Since ARSIs show similar efficacy for the treatment of PC, pharmacokinetic properties of these drugs and patient characteristics could help physicians decide which drug to select.

Unintentional combining enzalutamide with a moderate CYP2C8 inhibitor in a patient with metastatic castration-resistant prostate cancer: a case report.

Background: Enzalutamide, registered for the treatment of metastatic castration-resistant prostate cancer (mCRPC), is an inducer of multiple CYP-enzymes. Enzalutamide itself is mainly converted by CYP2C8 to the active metabolite N-desmethylenzalutamide (NDME). Due to a pharmacokinetic interaction, combining enzalutamide with a moderate CYP2C8 inhibitor might result in higher enzalutamide concentrations.

RNA Biomarkers as a Response Measure for Survival in Patients with Metastatic Castration-Resistant Prostate Cancer.

Treatment evaluation in metastatic castration-resistant prostate cancer is challenging. There is an urgent need for biomarkers to discriminate short-term survivors from long-term survivors, shortly after treatment initiation. Thereto, the added value of early RNA biomarkers on predicting progression-free survival (PFS) and overall survival (OS) were explored.

Management of drug-drug interactions of targeted therapies for haematological malignancies and triazole antifungal drugs.

Over the past 10 years, the number of targeted therapies for haematological malignancies has substantially increased, and many new drugs have entered the market. Many of these therapies have shown improved disease-free survival and reduced toxicity compared with existing treatments, especially in older patients. However, most of these new drugs undergo extensive hepatic metabolism and exhibit moderate to severe drug-drug interactions with triazole antifungal agents, which are essential for the prophylaxis and long-term treatment of invasive fungal infections.

The effect of chemotherapy on the exposure-response relation of abiraterone in metastatic castration-resistant prostate cancer.

Aims: To assess whether the exposure-response relation for abiraterone is different in pre-chemotherapy patients compared to post-chemotherapy patients with metastatic castration-resistant prostate cancer (mCRPC).

Methods: Data were collected from three clinical studies in mCRPC patients treated with abiraterone acetate. Cox regression analysis was used to determine the relation between abiraterone exposure and survival (progression-free survival [PFS] and overall survival [OS]).

Deep and ongoing response of castrate-resistant prostate cancer on very low-dose enzalutamide in an elderly chemotherapy-naïve patient: a case report.

Background: Enzalutamide is an orally administered drug that blocks signaling in the androgen receptor with clinical activity in both chemotherapy-naive and post-chemotherapy patients with castrate-resistant prostate cancer (CRPC). Enzalutamide is generally well-tolerated, but dose reductions are nonetheless needed in case of side effects.

Case: An 82-year-old patient with chemotherapy-naive metastatic castration-resistant prostate cancer was treated with a very low dose of 40 mg enzalutamide once daily.

Liquid biopsy reveals KLK3 mRNA as a prognostic marker for progression free survival in patients with metastatic castration-resistant prostate cancer undergoing first-line abiraterone acetate and prednisone treatment.

Circulating RNAs extracted from liquid biopsies represent a promising source of cancer- and therapy-related biomarkers. We screened whole blood from patients with metastatic castration-resistant prostate cancer (mCRPC) following their first-line treatment with abiraterone acetate and prednisone (AA-P) to identify circulating RNAs that may correlate with progression-free survival (PFS). In a prospective multicenter observational study, 53 patients with mCRPC were included after they started first-line AA-P treatment.

A Systematic Review and Meta-Analysis on the Predictive Value of Cell-Free DNA-Based Androgen Receptor Copy Number Gain in Patients With Castration-Resistant Prostate Cancer.

Purpose: It has been suggested that androgen receptor copy number gain ( gain) detected in cell-free DNA (cfDNA) can predict treatment response to androgen receptor signaling inhibitors (ARSIs) in patients with castration-resistant prostate cancer (CRPC). But it is unclear whether cfDNA-based gain is a true resistance mechanism to ARSIs or mainly a reflection of the tumor burden. In this systematic review, we aim to summarize current literature and comment on the potential of cfDNA-based gain as a predictive biomarker to guide therapy choices.

Prognostic Value of Novel Liquid Biomarkers in Patients with Metastatic Castration-Resistant Prostate Cancer Treated with Enzalutamide: A Prospective Observational Study.

Background: Several treatment options were recently added for metastatic castration-resistant prostate cancer (mCRPC). However, response to therapy is variable, and biomarkers that can guide treatment selection and response evaluation are lacking. Circulating RNAs are a promising source of biomarkers.

Clinical utility of emerging biomarkers in prostate cancer liquid biopsies.

: Prostate cancer (PCa) is one of the most common malignancies in men and a major cause of cancer deaths among men worldwide. Prostate specific antigen (PSA) monitoring and histopathological examination of tumor biopsies remain gold standards in PCa diagnostics. These clinical parameters are not well suited for patient stratification, predicting and monitoring treatment response.

[Drug-facilitated sexual assault; frequently used substances, symptoms and toxicological investigation].

Drug-facilitated sexual assault (DFSA) is a term used to describe incidents of sexual assault in which the victim is incapacitated and/or unable to provide consent to the sexual act as a result of drug or alcohol consumption. There are two types: 'proactive' in which the victim is covertly administered an incapacitating or disinhibiting substance by an assailant for the purpose of sexual assault; and 'opportunistic' in which a perpetrator engages in sexual activity with a victim who is profoundly intoxicated by his or her actions, to the point of near or actual unconsciousness. Alcohol is the drug most commonly found in alleged sexual assault cases.

A non-interventional retrospective cohort study of the interaction between methotrexate and proton pump inhibitors or aspirin.

Introduction: Methotrexate (MTX) is an antifolate drug, which is frequently used in the treatment of cancer. Proton pump inhibitors (PPIs) could delay the elimination of plasma MTX in high-dose MTX therapy by inhibition of tubular secretion, which could lead to MTX toxicity. However, the evidence of the clinical relevance of this drug-drug interaction is inconsistent.

[Overdenture prostheses on implants versus complete dentures].

Objective: To establish the treatment outcome of implant retained overdentures (IRD) versus complete dentures (CD) in which the outcome assessment focuses on the patient's subjective evaluation ('denture-satisfaction and chewing ability').

Design: A multicenter randomized clinical trial (prospective).

Setting: The department of Oral Function and Prosthetic Dentistry of the University of Nijmegen, the department of Oral and Maxillofacial Surgery of the University Hospital Nijmegen and the department of Oral and Maxillofacial Surgery and Maxillofacial Prosthodontics of the University Hospital Groningen.

[Comparison of dental implant systems for mandibular overdentures].

Objective: To compare three implant systems in patients with severely resorbed mandibles 1 year after insertion of the mandibular denture.

Design: A prospective multicenter randomized clinical trial.

Setting: Centers at University of Nijmegen and Groningen.

Construction of a clinical implant performance scale for implant systems with overdentures with the Delphi method.

Statement Of Problem: The success of an implant system is often judged on the survival rate of the separate implants. This does not give a complete view of the "real" success of a system. To make that possible the total clinical performance, surgical and prosthetic, has to be considered.

A controlled clinical trial of implant-retained mandibular overdentures: clinical aspects.

In a controlled clinical trial, treatment effects of mandibular overdentures on two different implant-systems in edentulous patients were compared one year after insertion of the new dentures. The implant-systems used were the Brånemark system (Brå) and the IMZ-system. Treatment was randomly assigned to 60 patients according to a balanced allocation method.