Rob ter Heine
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View article: Optimizing lazertinib therapy through GSTM1 genotyping: a strategy to reduce excess drug exposure and potential toxicity
Optimizing lazertinib therapy through GSTM1 genotyping: a strategy to reduce excess drug exposure and potential toxicity Open
Purpose The combination of lazertinib and amivantamab has shown superior efficacy over first line osimertinib in EGFR-mutated metastatic non-small cell lung cancer, but is associated with significant toxicity and high costs. Lazertinib exp…
View article: Kinetics and hierarchy of TLR-4 mediated signaling leading to IL-6 release
Kinetics and hierarchy of TLR-4 mediated signaling leading to IL-6 release Open
Acute systemic inflammatory disorders, such as cytokine release syndrome or sepsis, remain among the leading causes of mortality. To better understand early inflammatory dynamics, we developed an ex vivo model using human peripheral blood …
View article: Eco Friendly and Budget Smart: An Economic and Environmental Evaluation of Alternative PD-1 and PD-L1 Inhibitor Dosing Regimens
Eco Friendly and Budget Smart: An Economic and Environmental Evaluation of Alternative PD-1 and PD-L1 Inhibitor Dosing Regimens Open
These findings suggest that optimizing dosing strategies can yield meaningful economic and environmental benefits in ICI therapy while maintaining drug exposure within levels defined by US Food and Drug Administration criteria or broader t…
View article: TDM-Based Tailored Dosing of Durvalumab in Lung Cancer Patients: A Comprehensive Population Pharmacokinetic–Pharmacoeconomic Evaluation
TDM-Based Tailored Dosing of Durvalumab in Lung Cancer Patients: A Comprehensive Population Pharmacokinetic–Pharmacoeconomic Evaluation Open
View article: Early pembrolizumab clearance as prognostic biomarker for non‐response in patients with advanced non‐small cell lung cancer
Early pembrolizumab clearance as prognostic biomarker for non‐response in patients with advanced non‐small cell lung cancer Open
Immune checkpoint inhibitors have improved survival rates in patients with advanced‐stage non‐small cell lung cancer; however, the majority obtain no long‐term benefits. We investigated pembrolizumab clearance as an early prognostic biomar…
View article: Model-Informed Precision Dosing of Eculizumab in Patients with Paroxysmal Nocturnal Hemoglobinuria
Model-Informed Precision Dosing of Eculizumab in Patients with Paroxysmal Nocturnal Hemoglobinuria Open
ClincialTrials.gov identifier: NCT04079257.
View article: Population pharmacokinetics and optimized dosing of cefuroxime in critically ill patients
Population pharmacokinetics and optimized dosing of cefuroxime in critically ill patients Open
Cefuroxime is a second‐generation cephalosporin widely used in the intensive care unit (ICU). ICU patients have high variability in interpatient pharmacokinetics (PK), but the extent of this variation is unclear. We performed an observatio…
View article: Folinic Acid Prophylaxis and Dose Adjustments Enable Safe Treatment with Pemetrexed in Patients with Renal Impairment
Folinic Acid Prophylaxis and Dose Adjustments Enable Safe Treatment with Pemetrexed in Patients with Renal Impairment Open
Pemetrexed is a cornerstone in chemo(immunotherapy) of non‐small cell lung cancer and mesothelioma; however, it is contraindicated in patients with renal impairment due to severe toxicity concerns. Therefore, a large proportion of patients…
View article: Ex vivo pembrolizumab pharmacology for personalized PD-1 inhibitor therapy reveals a critical gap between receptor occupancy and T cell functionality
Ex vivo pembrolizumab pharmacology for personalized PD-1 inhibitor therapy reveals a critical gap between receptor occupancy and T cell functionality Open
We highlight the importance of evaluating T cell functionality alongside PD-1 receptor occupancy. We identified PD-1-induced modulation of phosphorylation of proximal signalling molecules as potential predictors for ICI treatment response …
View article: Pharmacokinetic Study of Carboplatin Using Various Overweight-Correcting Dosing Algorithms and Biomarkers in Patients With Varying BMI Categories
Pharmacokinetic Study of Carboplatin Using Various Overweight-Correcting Dosing Algorithms and Biomarkers in Patients With Varying BMI Categories Open
Background: The Cockcroft–Gault (CG) formula is more likely to overestimate renal function and carboplatin dosing in patients who are overweight. In this prospective pharmacokinetic study, the use of an adjusted Cockcroft–Gault formula (aC…
View article: The Toxicity Profile of Pemetrexed in Non-Small Cell Lung Cancer Patients With Moderate Renal Impairment: A Retrospective Cohort Study
The Toxicity Profile of Pemetrexed in Non-Small Cell Lung Cancer Patients With Moderate Renal Impairment: A Retrospective Cohort Study Open
Pemetrexed treatment of NSCLC patients with moderate renal impairment was associated with high incidence of hematological toxicity, hospitalization, dose reduction, and treatment discontinuation. These results highlight the necessity of de…
View article: Opportunities for Precision Dosing of Cytotoxic Drugs in Non-Small Cell Lung Cancer: Bridging the Gap in Precision Medicine
Opportunities for Precision Dosing of Cytotoxic Drugs in Non-Small Cell Lung Cancer: Bridging the Gap in Precision Medicine Open
View article: Model-informed development of a cost-saving dosing regimen for enfortumab vedotin
Model-informed development of a cost-saving dosing regimen for enfortumab vedotin Open
Aim Enfortumab vedotin is an antibody-drug conjugate (ADC) that has been approved for locally advanced or metastatic urothelial cancer, as monotherapy and in combination with pembrolizumab, and has shown significant benefit in progression-…
View article: Model-informed repurposing of eliglustat for treatment and prophylaxis of Shiga toxin-producing Escherichia coli hemolytic-uremic syndrome (STEC-HUS) in children
Model-informed repurposing of eliglustat for treatment and prophylaxis of Shiga toxin-producing Escherichia coli hemolytic-uremic syndrome (STEC-HUS) in children Open
Background Shiga toxin-producing Escherichia coli hemolytic-uremic syndrome (STEC-HUS) is a severe illness predominantly affecting young children, with limited treatment options beyond supportive care. Eliglustat, approved for Gaucher dise…
View article: Very Early Health Technology Assessment for Potential Predictive Biomarkers in the Treatment of Advanced Non-Small Cell Lung Cancer
Very Early Health Technology Assessment for Potential Predictive Biomarkers in the Treatment of Advanced Non-Small Cell Lung Cancer Open
Our study highlights the importance of careful de-implementation of ICI-treatments in advanced NSCLC, balancing costs reductions and side effects without comprising survival. In the pembrolizumab-carboplatin-paclitaxel treatment regimen, t…
View article: Differential effects of C5 inhibition, C3 inhibition, and alternative pathway inhibition on bacterial killing in vitro
Differential effects of C5 inhibition, C3 inhibition, and alternative pathway inhibition on bacterial killing in vitro Open
Contains fulltext : 317901.pdf (Publisher’s version ) (Open Access)
View article: Long‐term effects of influenza and Bacille Calmette–Guérin vaccination on systemic inflammation
Long‐term effects of influenza and Bacille Calmette–Guérin vaccination on systemic inflammation Open
Objective Chronic systemic inflammation can lead to metabolic, cardiovascular and neurodegenerative complications, but the factors influencing it are incompletely understood. In this study, we evaluated several factors, including Bacille C…
View article: Patients in Clinical Trials are Sub‐Optimally Protected for Drug–Drug Interactions: A Call for Action
Patients in Clinical Trials are Sub‐Optimally Protected for Drug–Drug Interactions: A Call for Action Open
Contains fulltext : 320576.pdf (Publisher’s version ) (Open Access)
View article: Polyradiculitis as a Neurological Complication Associated with Adagrasib: A Case Report
Polyradiculitis as a Neurological Complication Associated with Adagrasib: A Case Report Open
Introduction: Adagrasib is an upcoming anticancer treatment for KRAS G12C-mutated non-small-cell lung carcinoma, colorectal cancer and potentially other solid tumors harboring this mutation. It is generally well-tolerated and reports of ne…
View article: Azithromycin in severe malaria bacterial co-infection in African children (TABS-PKPD): a phase II randomised controlled trial
Azithromycin in severe malaria bacterial co-infection in African children (TABS-PKPD): a phase II randomised controlled trial Open
Background African children with severe malaria are at increased risk of non-typhoidal salmonellae co-infection. Broad-spectrum antibiotics are recommended by guidelines but the optimal class and dose have not been established. We investig…
View article: Outcomes from the International Society of Nephrology Hemolytic Uremic Syndromes International Forum
Outcomes from the International Society of Nephrology Hemolytic Uremic Syndromes International Forum Open
View article: A comparison of the renal function biomarkers serum creatinine, pro-enkephalin and cystatin C to predict clearance of pemetrexed
A comparison of the renal function biomarkers serum creatinine, pro-enkephalin and cystatin C to predict clearance of pemetrexed Open
Introduction For drugs with a narrow therapeutic window, there is a delicate balance between efficacy and toxicity, thus it is pivotal to administer the right dose from the first administration onwards. Exposure of pemetrexed, a cytotoxic …
View article: Pharmacokinetic study of carboplatin using various overweight-correcting dosing algorithms and biomarkers in patients with varying BMI categories
Pharmacokinetic study of carboplatin using various overweight-correcting dosing algorithms and biomarkers in patients with varying BMI categories Open
PURPOSE In overweight patients, the Cockcroft-Gault (CG) formula is more likely to overestimate renal function and carboplatin dosing. In this prospective pharmacokinetic study, we evaluated the use of an adjusted Cockcroft-Gault formula (…
View article: Model-informed dose optimization of mycophenolic acid in pediatric kidney transplant patients
Model-informed dose optimization of mycophenolic acid in pediatric kidney transplant patients Open
Purpose We aimed to develop and evaluate a population PK model of mycophenolic acid (MPA) in pediatric kidney transplant patients to aid MPA dose optimization. Methods Data were collected from pediatric kidney transplant recipients from a …
View article: Development and validation of an ultra‐performance liquid chromatography–tandem mass spectrometry method to quantify the small molecule inhibitors adagrasib, alectinib, brigatinib, capmatinib, crizotinib, lorlatinib, selpercatinib, and sotorasib in human plasma
Development and validation of an ultra‐performance liquid chromatography–tandem mass spectrometry method to quantify the small molecule inhibitors adagrasib, alectinib, brigatinib, capmatinib, crizotinib, lorlatinib, selpercatinib, and sotorasib in human plasma Open
Small molecule inhibitors (SMIs) are increasingly being used in the treatment of non‐small cell lung cancer. To support pharmacokinetic research and clinical treatment monitoring, our aim was to develop and validate an ultra‐performance li…
View article: An Evidence-Based Rationale for Dose De-escalation of Subcutaneous Atezolizumab
An Evidence-Based Rationale for Dose De-escalation of Subcutaneous Atezolizumab Open
We have developed and evaluated two alternative dosing regimens that resulted in a cost reduction. Our weight-based dosing regimen can be directly implemented and complies with FDA guidelines for alternative dosing regimens of PD-L1 inhibi…
View article: A sub-pharmacological test dose does not predict individual docetaxel exposure in prostate cancer patients
A sub-pharmacological test dose does not predict individual docetaxel exposure in prostate cancer patients Open
View article: Model-Informed Development of a Cost-Saving Dosing Regimen for Sacituzumab Govitecan
Model-Informed Development of a Cost-Saving Dosing Regimen for Sacituzumab Govitecan Open
View article: Proactive monitoring of drug–drug interactions between direct oral anticoagulants and small-molecule inhibitors in patients with non-small cell lung cancer
Proactive monitoring of drug–drug interactions between direct oral anticoagulants and small-molecule inhibitors in patients with non-small cell lung cancer Open
Background Small-molecule inhibitors (SMIs) have revolutionised the treatment of non-small cell lung cancer (NSCLC). However, SMI-induced drug–drug interactions (DDIs) with frequently co-administered direct oral anticoagulants (DOACs), inc…
View article: Personalized Antifungal Therapy Through Model-Informed Precision Dosing of Posaconazole
Personalized Antifungal Therapy Through Model-Informed Precision Dosing of Posaconazole Open