Related Experiment Video
Updated: Sep 19, 2025
Detection of a Circulating MicroRNA Custom Panel in Patients with Metastatic Colorectal Cancer
Published on: March 14, 2019
Exploring the Association Between Intra-Patient Variability in Trough Concentration of Pazopanib and Clinical
Amy Rieborn1, Eline L Giraud1,2, Teun van Gelder1
1Department of Clinical Pharmacy & Toxicology, Leiden University Medical Center, Leiden, The Netherlands.
Abstract:
Pazopanib is an oral tyrosine kinase inhibitor used in patients with either metastatic renal cell carcinoma or soft tissue sarcoma. Pazopanib has a high interindividual variability in pharmacokinetics and pharmacodynamics and a well-established exposure-response relationship. Therefore, therapeutic drug monitoring is recommended to improve the efficacy-toxicity balance. Intra-patient variability in pazopanib pharmacokinetics is moderate with a mean of 24.7%. In other fields, such as transplantation medicine, a high intra-patient variability of immunosuppressive drugs has previously been associated with worse outcomes. Whether this also applies to therapeutic modalities in oncology is unknown. The aim of this study was to explore the relationship between pazopanib intra-patient variability and clinical outcomes. Data from patients diagnosed with either metastatic renal cell carcinoma or soft tissue sarcoma treated with pazopanib guided by routine therapeutic drug monitoring with at least three available pazopanib trough concentrations were retrieved. Non-dose corrected estimated trough concentrations were used to calculate intra-patient variability. Among 144 patients, median intra-patient variability was 30.2%. The high intra-patient variability group (intra-patient variability > 30.2%) was at risk for worse progression-free survival (HR 1.42; 95% CI 0.85-2.35) and overall survival (HR 2.17; 95% CI 1.10-4.29) in patients with renal cell carcinoma. No association between a high intra-patient variability and clinical outcomes for patients with soft tissue sarcoma could be established. Our results show that high intra-patient variability is associated with poorer treatment outcomes. A high intra-patient variability urges the treating clinician to address therapy adherence, drug-drug and food-drug interactions, and improve chances for optimal treatment outcome.
Insights
High intra-patient variability in pazopanib pharmacokinetics is linked to worse survival outcomes in renal cell carcinoma patients. This highlights the need to address adherence and interactions for better treatment results.
Area of Science:
- Pharmacology
- Oncology
- Clinical Therapeutics
Background:
- Pazopanib, an oral tyrosine kinase inhibitor, treats metastatic renal cell carcinoma and soft tissue sarcoma.
- It exhibits significant inter-individual variability in pharmacokinetics and pharmacodynamics, with a known exposure-response relationship.
- Therapeutic drug monitoring is recommended for pazopanib to optimize efficacy and minimize toxicity.
Purpose of the Study:
- To investigate the association between intra-patient variability in pazopanib pharmacokinetics and clinical outcomes in cancer patients.
- To determine if high intra-patient variability, previously linked to poor outcomes in transplantation, affects cancer treatment.
- To explore this relationship specifically in patients with metastatic renal cell carcinoma and soft tissue sarcoma.
Main Methods:
- Retrospective analysis of 144 patients with metastatic renal cell carcinoma or soft tissue sarcoma treated with pazopanib.
- Utilized routine therapeutic drug monitoring data, requiring at least three pazopanib trough concentrations per patient.
- Calculated intra-patient variability using non-dose-corrected estimated trough concentrations.
Main Results:
- Median intra-patient variability in pazopanib levels was 30.2%.
- Patients with high intra-patient variability ( > 30.2%) showed increased risk for worse progression-free survival and overall survival in renal cell carcinoma.
- No significant association was found between high intra-patient variability and clinical outcomes in soft tissue sarcoma patients.
Conclusions:
- High intra-patient variability in pazopanib pharmacokinetics is associated with poorer survival outcomes in renal cell carcinoma.
- This finding suggests that clinicians should investigate adherence, drug-drug, and food-drug interactions when high variability is observed.
- Addressing these factors may improve treatment outcomes for patients receiving pazopanib.
More Related Videos
12:22The Use of Reverse Phase Protein Arrays RPPA to Explore Protein Expression Variation within Individual Renal Cell Cancers
Published on: January 22, 2013
09:29Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies
Published on: September 30, 2016
Related Concept Videos
01:29Factors Affecting Protein-Drug Binding: Patient-Related Factors
Age stands as a key determinant in protein-drug binding. Neonates, characterized by low albumin content, experience heightened concentrations of unbound drugs such as phenytoin and...
02:50Combination Therapies and Personalized Medicine
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
01:09Factors Affecting Renal Clearance: Drug Distribution and Drug Interactions
One important factor is the relationship between renal clearance and the apparent volume of distribution. Renal clearance tends to be inversely proportional to the apparent volume of distribution. Drugs with an extensive distribution volume or those...