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Updated: Sep 6, 2025
Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia
Published on: September 18, 2013
Relevance of Therapeutic Drug Monitoring of Tyrosine Kinase Inhibitors in Routine Clinical Practice: A Pilot Study
Vanesa Escudero-Ortiz1,2, Vanessa Domínguez-Leñero3, Ana Catalán-Latorre1
1Plataforma de Oncología, Hospital Quirónsalud Torrevieja, 03184 Torrevieja, Spain.
Introduction:
The main goal of treatment in cancer patients is to achieve the highest therapeutic effectiveness with the least iatrogenic toxicity. Tyrosine kinase inhibitors (TKIs) are anticancer oral agents, usually administered at fixed doses, which present high inter- and intra-individual variability due to their pharmacokinetic characteristics. Therapeutic drug monitoring (TDM) can be used to optimize the use of several types of medication.
Objective:
We evaluated the use of TDM of TKIs in routine clinical practice through studying the variability in exposure to erlotinib, imatinib, lapatinib, and sorafenib and dose adjustment.
Materials And Methods:
We conducted a retrospective analytical study involving patients who received treatment with TKIs, guided by TDM and with subsequent recommendation of dose adjustment. The quantification of the plasma levels of the different drugs was performed using high-performance liquid chromatography (HPLC). The Clinical Research Ethics Committee of the Hospital Quirónsalud Torrevieja approved this study.
Results:
The inter-individual variability in the first cycle and in the last monitored cycle was 46.2% and 44.0% for erlotinib, 48.9 and 50.8% for imatinib, 60.7% and 56.0% for lapatinib and 89.7% and 72.5% for sorafenib. Relationships between exposure and baseline characteristics for erlotinib, imatinib, lapatinib and sorafenib were not statistically significant for any of the variables evaluated (weight, height, body surface area (BSA), age and sex). Relationships between height (p = 0.021) and BSA (p = 0.022) were statistically significant for sorafenib. No significant relationships were observed between Ctrough and progression-free survival (PFS) or overall survival (OS) for any drug, except in the case of sunitinib (correlation between Ctrough and PFS p = 0.023) in the exposure-efficacy analysis.
Conclusions:
Erlotinib, imatinib, lapatinib and sorafenib show large inter-individual variability in exposure. TDM entails a significant improvement in exposure and enables more effective and safe use of TKIs in routine clinical practice.
Insights
Therapeutic drug monitoring (TDM) of tyrosine kinase inhibitors (TKIs) reveals significant inter-individual variability in drug exposure. TDM optimizes TKI therapy, improving effectiveness and safety in cancer treatment.
Area of Science:
- Pharmacology
- Oncology
- Clinical Pharmacy
Background:
- Tyrosine kinase inhibitors (TKIs) are oral anticancer agents with significant inter- and intra-individual pharmacokinetic variability.
- Optimizing cancer treatment effectiveness while minimizing toxicity is a primary clinical goal.
- Therapeutic drug monitoring (TDM) is a strategy to personalize medication use.
Purpose of the Study:
- To assess the clinical utility of TDM for four TKIs: erlotinib, imatinib, lapatinib, and sorafenib.
- To evaluate the variability in drug exposure and the impact of dose adjustments guided by TDM.
- To explore relationships between TKI exposure, patient characteristics, and clinical outcomes.
Main Methods:
- A retrospective analytical study of patients undergoing TKI treatment with TDM-guided dose adjustments.
- Quantification of plasma drug levels using high-performance liquid chromatography (HPLC).
- Ethical approval obtained from the Hospital Quirónsalud Torrevieja Clinical Research Ethics Committee.
Main Results:
- High inter-individual variability in drug exposure was observed for all studied TKIs, with sorafenib showing the highest (up to 89.7%).
- No statistically significant relationships were found between baseline patient characteristics (weight, height, BSA, age, sex) and TKI exposure, except for height and BSA with sorafenib.
- No significant correlation between trough concentrations (Ctrough) and progression-free survival (PFS) or overall survival (OS) was observed for most TKIs, with a noted exception for sunitinib and PFS.
Conclusions:
- Erlotinib, imatinib, lapatinib, and sorafenib exhibit substantial inter-individual variability in patient exposure.
- TDM significantly improves TKI exposure, leading to more effective and safer clinical application.
- TDM is a valuable tool for optimizing the use of TKIs in routine cancer care.
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