A5019741685- Colorectal Cancer Treatments and Studies
- Pancreatic and Hepatic Oncology Research
- Cancer therapeutics and mechanisms
- Biochemical and Molecular Research
- Cancer Treatment and Pharmacology
- Lung Cancer Treatments and Mutations
- Hepatocellular Carcinoma Treatment and Prognosis
- Gastric Cancer Management and Outcomes
- Intraperitoneal and Appendiceal Malignancies
- Esophageal Cancer Research and Treatment
- Drug Transport and Resistance Mechanisms
- Appendicitis Diagnosis and Management
- Lung Cancer Research Studies
- Chemotherapy-related skin toxicity
- Ovarian cancer diagnosis and treatment
- Gastrointestinal Tumor Research and Treatment
- Neutropenia and Cancer Infections
- Pharmacogenetics and Drug Metabolism
- Lymphoma Diagnosis and Treatment
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Prostate Cancer Treatment and Research
- PI3K/AKT/mTOR signaling in cancer
- Esophageal and GI Pathology
- Frailty in Older Adults
- Medical Imaging Techniques and Applications
Erasmus MC Cancer Institute
2016-2025
Erasmus MC
2015-2025
Amsterdam UMC Location University of Amsterdam
2017
Sint Franciscus Gasthuis
2017
The Netherlands Cancer Institute
2017
Leiden University Medical Center
2017
Astellas Pharma (Netherlands)
2015
In clinical practice, 25–30% of the patients treated with fluoropyrimidines experience severe fluoropyrimidine‐related toxicity. Extensively clinically validated DPYD genotyping tests are available to identify at risk toxicity due decreased activity dihydropyrimidine dehydrogenase (DPD), rate limiting enzyme in fluoropyrimidine metabolism. April 2020, European Medicines Agency recommended that, as an alternative for genotype‐based testing DPD deficiency, also phenotype based on pretreatment...
DPYD-guided fluoropyrimidine dosing improves patient safety in carriers of DPYD variant alleles. However, the impact on treatment outcome these patients is largely unknown. Therefore, progression-free survival (PFS) and overall (OS) were compared between treated with a reduced dose wild-type controls receiving full retrospective matched-pair analysis.Data from prospective multicenter study (ClinicalTrials.gov identifier: NCT02324452) which received 25% (c.1236G>A c.2846A>T) or 50% (DPYD*2A...
Abstract Background Despite the implementation of DPYD genotype‐guided dosing, approximately 1 in 3 patients receiving fluoropyrimidine‐containing chemotherapy continues to experience severe toxicity. While clinical studies have demonstrated a favorable tolerance among highly selected fit older adults, real‐world shown an increased risk Objective To identify predictors toxicity or treatment deintensification wild‐type adults chemotherapy. Method Patients wild type for four tested variants,...
Abstract Background Patients with colorectal peritoneal metastases who are not eligible for cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) owing to extensive disease have a poor prognosis. It was hypothesized that these patients may benefit from the addition of irinotecan standard palliative systemic chemotherapy. Methods This classical 3 + phase I dose-escalation trial in were CRS-HIPEC. Intraperitoneal administered every 2 weeks, concomitantly FOLFOX...
Introduction Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) has become standard of care for patients with peritoneal metastases colorectal origin a low/moderate abdominal disease load. In case cancer index (PCI) score >20, CRS-HIPEC is not considered to be beneficial. Patients PCI >20 are currently offered palliative systemic chemotherapy. Previous studies have shown that less effective against than it haematogenous spread cancer. It suggested may...
Abstract Background The Alpe-DPD study (NCT02324452) demonstrated that prospective genotyping and dose-individualization using four alleles in DPYD ( *2A/rs3918290, c.1236G > A/rs75017182, c.2846A T/rs67376798 c.1679 T G/rs56038477) can mitigate the risk of severe fluoropyrimidine toxicity. However, this could not prevent all toxicities. goal was to identify additional genetic variants, both inside outside , may contribute Methods Biospecimens data from were used. Exon sequencing...
Preclinical data suggests that protein and calorie restriction (PCR) might improve treatment tolerability without impairing antitumor efficacy. Therefore, we have studied the influence of PCR on irinotecan pharmacokinetics toxicity. In this crossover trial, patients with liver metastases solid tumors were included randomized to preceded by 5 days (~ 30% caloric ~ 70% restriction) during first cycle a second normal diet or vice versa. Pharmacokinetic blood sampling biopsies both healthy...
Regorafenib exposure could potentially be influenced by an interaction with acid‐reducing drugs. In this crossover trial, patients were randomized into two sequence groups consisting of three phases: regorafenib intake alone, concomitant esomeprazole, and esomeprazole 3 hours prior. The primary end point was the relative difference ( RD ) in geometric means for 0–24‐hour area under concentration‐time curve AUC 0–24h analyzed a linear mixed model 14 patients. alone 55.9 μg·hour/mL...
Background: Capecitabine is generally dosed based on body surface area (BSA). This dosing strategy has several limitations; however, evidence for alternative strategies lacking. Therefore, we analyzed the toxicity and effectiveness of fixed-dose capecitabine compared this with a BSA-based dose in large set patients. Methods: Patients treated between 2003 2015 were studied. A comparable group patients, BSA, was chosen as control cohort. total two combined scores used: capecitabine-specific...
For imatinib, a relationship between systemic exposure and clinical outcome has been suggested. Importantly, imatinib concentrations are not stable decrease over time, for which several mechanisms have In this study, we investigated if in alpha-1 acid glycoprotein (AGP) is the main cause of lowering time.We prospectively measured trough concentration (C min) values 28 patients with gastrointestinal stromal tumours, at 1, 3 12 months after start treatment. At same time points, AGP levels were...
Many patients have advanced esophageal cancer at diagnosis. However, the most optimal treatment has not been identified. Therefore, we evaluated a weekly regimen of carboplatin (area under curve (AUC)) 4 and paclitaxel 100 mg/m2 as an induction or palliative treatment. All with (gastro)esophageal treated this between 2002–2018 were included. Exclusion criteria previous radiotherapy elsewhere. Data on toxicity, response, survival collected. Analyses performed in two groups: (iCT) chemotherapy...
Retrospective data suggest that gastric acid reduction by proton pump inhibitors (PPIs) impairs the dissolution and subsequent absorption of capecitabine, thus potentially reduces capecitabine exposure. Therefore, we examined prospectively effect esomeprazole on pharmacokinetics capecitabine. In this randomized crossover study, patients with cancer were assigned to 2 sequence groups, each consisting 3 phases: administration hours before (phase A), alone B), concomitant cola co‐administration...
Background: Data from previous work suggests that there is no correlation between systemic (plasma) paclitaxel exposure and efficacy in patients treated for esophageal cancer. In this trial, we investigated ATP-binding cassette efflux transporter expression intratumoral pharmacokinetics of to identify changes which could be a first sign chemoresistance. Methods: Patients with cancer carboplatin (± concomitant radiotherapy) were included. During the last cycle weekly paclitaxel, blood samples...
Around 20%-30% of patients treated with fluoropyrimidines develop severe treatment-related adverse events (AEs). These are mainly caused by deficiency dihydropyrimidine dehydrogenase, its main metabolizing enzyme. The DPYD*7 variant allele contains a frameshift mutation that leads to absence dehydrogenase. Clinical studies on this in lacking because low minor allelic frequency. However, the frequency is 56-times higher Dutch compared global population. This allowed us evaluate...
Background: The aim of this study was to investigate whether pretransplant tacrolimus (Tac) dose requirements patients scheduled undergo living donor kidney transplantation correlate with posttransplantation requirements. Methods: predictive value Tac (defined as the ratio predose concentration, C0, divided by total daily dose, D) pretransplantation on same parameter assessed retrospectively in a cohort 57 AB0-incompatible transplant recipients. These started immunosuppressive therapy 14...
3574 Background: Irinotecan is commonly used in the treatment of advanced colorectal and pancreatic cancer. The polymorphisms UGT1A1*28 (7 TA repeats) UGT1A1*93 (SNP -3156G > A) are significantly associated with increased systemic exposure irinotecan’s active metabolite SN-38 subsequently severe irinotecan-associated adverse-events (AEs) including (febrile) neutropenia diarrhea. Severe AEs may lead to hospitalization, loss quality life, delay and/or discontinuation. Nonetheless,...
Inter-individual variability in paclitaxel pharmacokinetics may play a role the response to chemotherapy. Therefore, we studied association between clearance and treatment patients with esophageal cancer. All who received (plus carboplatin) for cancer 2007 2013 were included. The was given as neoadjuvant chemoradiotherapy (nCRT), induction chemotherapy (iCT), or palliative (pCT). assessed by tumor regression grade (TRG) RECIST1.1 criteria, respectively. unbound (CL) estimated NONMEM....