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Optimizing the dose in cancer patients treated with imatinib, sunitinib and pazopanib
Nienke A G Lankheet1, Ingrid M E Desar2, Sasja F Mulder2
1Department of Pharmacy, Radboud University Medical Center, Nijmegen, Netherlands.
Aim:
Fixed dose oral tyrosine kinase inhibitors imatinib, sunitinib and pazopanib show a high interpatient variability in plasma exposure. A relationship between plasma exposure and treatment outcome has been established, which supports the rationale for dose optimization of these drugs. The aim of this study was to monitor how many patients reached adequate trough levels after therapeutic drug monitoring-based dose optimization in daily practice.
Methods:
A cohort study was performed in patients treated with imatinib, sunitinib or pazopanib of whom follow-up drug levels were measured between August 2012 and April 2016. Patients' characteristics were collected by reviewing electronic patient records. Drug levels were measured using high-performance liquid chromatography coupled with tandem mass spectrometry and trough levels were estimated using a predefined algorithm. Dose interventions were proposed based on trough levels.
Results:
In total, 396 trough levels were determined in 109 patients. Median sample frequency per patient was 3. During the first measurement only 38% of patients showed trough levels within the predefined target ranges despite standard dosing; 52% of the patients showed drug levels below and 10% above the target range. In 35 out of 41 patients (85%) dose interventions led to adequate trough levels. Eventually, 64% of the total cohort reached adequate trough levels.
Conclusions:
Dose optimization proved an effective tool to reach adequate trough levels in patients treated with imatinib, sunitinib and pazopanib. The percentage of patients with adequate trough levels increased from 38 to 64%. Therapeutic drug monitoring may add to the improvement of efficacy and reduction of toxicity and costs of these treatments.
Insights
Therapeutic drug monitoring and dose optimization increased adequate drug trough levels in patients receiving imatinib, sunitinib, and pazopanib from 38% to 64%. This approach enhances treatment efficacy and safety.
Area of Science:
- Pharmacology
- Oncology
- Clinical Pharmacy
Background:
- Tyrosine kinase inhibitors (TKIs) like imatinib, sunitinib, and pazopanib exhibit significant interpatient variability in plasma exposure.
- Established links between plasma exposure and treatment outcomes necessitate dose optimization for these TKIs.
Purpose of the Study:
- To evaluate the effectiveness of therapeutic drug monitoring (TDM)-guided dose optimization in achieving adequate trough plasma levels for patients on imatinib, sunitinib, and pazopanib in routine clinical practice.
Main Methods:
- A cohort study involving 109 patients treated with imatinib, sunitinib, or pazopanib.
- Measurement of drug trough levels using high-performance liquid chromatography coupled with tandem mass spectrometry.
- Dose adjustments were proposed based on TDM results.
Main Results:
- Initially, only 38% of patients achieved target trough levels with standard dosing.
- Following dose optimization, the percentage of patients reaching adequate trough levels increased to 64%.
- 85% of patients who underwent dose interventions achieved adequate trough levels.
Conclusions:
- Dose optimization guided by TDM is an effective strategy for reaching therapeutic trough levels in patients on imatinib, sunitinib, and pazopanib.
- TDM can potentially improve treatment efficacy, reduce toxicity, and lower healthcare costs associated with TKI therapy.
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