Systemic Treatment Strategies and Outcomes of Patients With Synchronous Peritoneal Metastases of Gastric Origin: A Nationwide Population-Based Study.

Background: Palliative systemic treatment is currently standard of care for metastatic gastric cancer. However, patients with peritoneal metastases of gastric origin are often underrepresented in clinical studies due to unmeasurable radiologic disease. This study describes the systemic treatment strategies and outcomes in patients with peritoneal metastases in a nationwide real-world setting.

Evaluating the Clinical Impact and Feasibility of Therapeutic Drug Monitoring of Pazopanib in a Real-World Soft-Tissue Sarcoma Cohort.

Introduction And Objective: Pazopanib is registered for metastatic renal cell carcinoma and soft-tissue sarcoma (STS). Its variable pharmacokinetic (PK) characteristics and narrow therapeutic range provide a strong rationale for therapeutic drug monitoring (TDM). Prior studies have defined target levels of drug exposure (≥ 20.

Reasons for non-feasibility of therapeutic drug monitoring of oral targeted therapies in oncology - an analysis of the closed cohorts of a multicentre prospective study.

Background: Therapeutic drug monitoring (TDM) - performing dose adjustments based on measured drug levels and established pharmacokinetic (PK) targets - could optimise treatment with drugs that show large interpatient variability in exposure. We evaluated the feasibility of TDM for multiple oral targeted therapies. Here we report on drugs for which routine TDM is not feasible.

The OCT2/MATE1 Interaction Between Trifluridine, Metformin and Cimetidine: A Crossover Pharmacokinetic Study.

Background And Objectives: Trifluridine/tipiracil, registered for the treatment of patients with metastatic gastric and colorectal cancer, is a substrate and inhibitor for the organic cation transporter 2 (OCT2) and the multidrug and toxin extrusion protein 1 (MATE1), which raises the potential for drug-drug interactions with other OCT2/MATE1 modulators. Therefore, we prospectively examined the effect of an OCT2/MATE1 inhibitor (cimetidine) and substrate (metformin) on the pharmacokinetics of trifluridine.

Methods: In this three-phase crossover study, patients with metastatic colorectal or gastric cancer were sequentially treated with trifluridine/tipiracil alone (phase A), trifluridine/tipiracil concomitant with metformin (phase B) and trifluridine/tipiracil concomitant with cimetidine (phase C).

Sunitinib for the treatment of metastatic gastrointestinal stromal tumors: the effect of TDM-guided dose optimization on clinical outcomes.

Background: Sunitinib is an oral anticancer drug approved for the treatment of among others gastrointestinal stromal tumor (GIST). Previous analyses demonstrated an exposure-response relationship at the standard dose, and minimum target levels of drug exposure have been defined above which better treatment outcomes are observed. Therapeutic drug monitoring (TDM) could be used as a tool to optimize the individual dose, aiming at sunitinib trough concentrations ≥37.

Intraperitoneal pharmacokinetics of systemic oxaliplatin, 5-fluorouracil and bevacizumab in patients with colorectal peritoneal metastases.

Background: Peritoneal metastases (PM) commonly occur in colorectal cancer patients. Systemic chemotherapy yields poor outcomes for these patients. It is hypothesised that traditional systemic chemotherapy is not very effective for this patient population.

Intraperitoneal chemotherapy for peritoneal metastases of gastric origin: a systematic review and meta-analysis.

Background: Gastric cancer with peritoneal metastases is associated with a dismal prognosis. Normothermic catheter-based intraperitoneal chemotherapy and normothermic pressurized intraperitoneal aerosol chemotherapy (PIPAC) are methods to deliver chemotherapy intraperitoneally leading to higher intraperitoneal concentrations of cytotoxic drugs compared to intravenous administration. We reviewed the effectiveness and safety of different methods of palliative intraperitoneal chemotherapy.

Staging laparoscopy in gastric cancer patients: From a Dutch nationwide Delphi consensus towards a standardized protocol.

Background: Staging laparoscopy is a common diagnostic tool in gastric cancer, but its performance varies widely. The aim of this study was to gain Dutch nationwide consensus regarding the indications for and execution of staging laparoscopy in patients with gastric cancer.

Methods: All surgeons in the Netherlands specialized in gastric cancer surgery (n = 52) were asked to participate in a Delphi consensus study.

Intraperitoneal irinotecan with concomitant FOLFOX and bevacizumab for patients with unresectable colorectal peritoneal metastases: protocol of the multicentre, open-label, phase II, INTERACT-II trial.

Introduction: The peritoneum is the second most affected organ for the dissemination of colorectal cancer (CRC). Patients with colorectal peritoneal metastases (CPM) face a poor prognosis, despite the majority of patients being treated with palliative systemic therapy. The efficacy of palliative systemic therapy is limited due to the plasma-peritoneum barrier.

Pharmacokinetic boosting of olaparib: A randomised, cross-over study (PROACTIVE-study).

Background: Pharmacokinetic (PK) boosting is the intentional use of a drug-drug interaction to enhance systemic drug exposure. PK boosting of olaparib, a CYP3A-substrate, has the potential to reduce PK variability and financial burden. The aim of this study was to investigate equivalence of a boosted, reduced dose of olaparib compared to the non-boosted standard dose.

Therapeutic Drug Monitoring of Kinase Inhibitors in Oncology.

Although kinase inhibitors (KI) frequently portray large interpatient variability, a 'one size fits all' regimen is still often used. In the meantime, relationships between exposure-response and exposure-toxicity have been established for several KIs, so this regimen could lead to unnecessary toxicity and suboptimal efficacy. Dose adjustments based on measured systemic pharmacokinetic levels-i.

CYP3A4*22 Genotype-Guided Dosing of Kinase Inhibitors in Cancer Patients.

Introduction: A genetic variant explaining a part of the exposure of many kinase inhibitors (KIs) is the single nucleotide polymorphism (SNP) CYP3A4*22, resulting in less CYP3A4 enzyme activity. The primary aim of this study was to investigate if the systemic exposure is non-inferior after a dose reduction of KIs metabolized by CYP3A4 in CYP3A4*22 carriers compared to patients without this SNP (i.e.

Intraperitoneal Chemotherapy for Unresectable Peritoneal Surface Malignancies.

Malignancies of the peritoneal cavity are associated with a dismal prognosis. Systemic chemotherapy is the gold standard for patients with unresectable peritoneal disease, but its intraperitoneal effect is hampered by the peritoneal-plasma barrier. Intraperitoneal chemotherapy, which is administered repeatedly into the peritoneal cavity through a peritoneal implanted port, could provide a novel treatment modality for this patient population.

Feasibility of therapeutic drug monitoring of sorafenib in patients with liver or thyroid cancer.

Introduction: Sorafenib is a tyrosine-kinase inhibitor approved for the treatment of renal cell carcinoma, hepatocellular carcinoma, thyroid carcinoma, and desmoid fibromatosis. As high inter-individual variability exists in exposure, there is a scientific rationale to pursue therapeutic drug monitoring (TDM). We investigated the feasibility of TDM in patients on sorafenib and tried to identify sub-groups in whom pharmacokinetically (PK) guided-dosing might be of added value.

Intraperitoneal paclitaxel for patients with primary malignant peritoneal mesothelioma: a phase I/II dose escalation and safety study-INTERACT MESO.

Introduction: Malignant peritoneal mesothelioma (MPM) is a rare, aggressive tumour arising primarily from the peritoneum. The only potentially curative treatment is cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). However, the majority of patients are not eligible to undergo this treatment.

Characteristics of COVID-19 infection and antibody formation in patients known at a tertiary immunology department.

Background: Knowledge about COVID-19 infections is expanding, although knowledge about the disease course and antibody formation in patients with an auto-immune disease or immunodeficiency is not fully unraveled yet. It could be hypothesized that immunodeficient patients, due to immunosuppressive drugs or their disease, have a more severe disease course due to their immunocompromised state. However, it could also be hypothesized that some of the immunosuppressive drugs protect against a hyperinflammatory state.

The value of anti-neutrophil cytoplasmic antibodies (ANCA) testing for the diagnosis of ANCA-associated vasculitis, a systematic review and meta-analysis.

The testing of anti-neutrophil cytoplasmic antibodies (ANCA) takes an important place in the diagnostic workup to ANCA-associated vasculitis (AAV). Nowadays, it is recommended to screen for the presence of PR3 and MPO specific antibodies first using immunoassay, without the need for ANCA measurement by indirect immunofluorescence (IIF). A literature search was performed to assess the diagnostic test value of ANCA IIF and PR3- and MPO-antibody immunoassay to diagnose AAV.