Oral oncolytics imatinib (IMN), sunitinib (SNN) and pazopanib (PZN) show a high interpatient variability in pharmacokinetics. For IMN, SNN and PZN 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 (Cmin) after dose optimization in daily practice.
An observational study was performed in a cohort of patients treated with IMN, SNN or PZN of whom multiple drug levels were measured between August 2012 and April 2016. Patients' characteristics were collected by reviewing medical records. Drug levels were measured using LC-MS/MS and Cmin were estimated using the algorithm of Wang et al.
396 trough levels were determined in 109 patients. Median sample frequency per patient was 3. During the first measurement only 38% of patients showed Cmin within the predefined target ranges: 52% of the patients showed a drug level below and 10% above target range. Dose interventions were proposed in 72 (66%) patients and implemented in 41 (38%) patients. In 35 out of 41 patients (85%) dose interventions led to an adequate Cmin. Eventually, 64% of the total cohort reached an adequate Cmin.
|Characteristics||Imatinib||(n = 70)||Sunitinib||(n = 12)||Pazopanib||(n = 27)||Total||(n = 109)|
|Drug levels (n)||290||75||31||396|
|Drug levels per patient median (range)||3 (2-13)||2 (2-8)||3 (2-3)||3 (2-13)|
|Adequate Cmin n (%)||29 (41)||42 (60)||7 (26)||20 (74)||5 (42)||8 (67)||41 (38)||70 (64)|
|Patients with interventions n (%)||20 (29)||17 (63)||4 (33)||41 (38)|
|Patients with adequate Cmin after intervention n (%)||19 (95)||13 (76)||3 (75)||35 (85)|
This study shows that dose optimization is an effective tool to reach adequate Cmin for patients treated with IMN, SNN and PZN. Initially, only 38% of patients had an adequate Cmin. Of the patients undergoing dose intervention 85% reached an adequate Cmin. Plasma exposure awareness might add to the improvement of efficacy and toxicity of patients treated with IMN, SNN and PZN.
Clinical trial identification
Legal entity responsible for the study
Radboud University Medical Center
All authors have declared no conflicts of interest.