Abstract
Simple SummaryRelationships between drug concentrations in blood and efficacy and/or toxicity have been reported for up to 80% of oral anticancer drugs (OADs). Most OADs exhibit highly variable drug concentrations at the approved dose. This may result in a significant proportion of patients with suboptimal drug concentrations. Therapeutic Drug Monitoring (TDM), which is dose optimization based on measured drug concentrations, can be used to personalize drug dosing with the overall goal to improve the benefit-risk ratio of anticancer drug treatment. The ON-TARGET study aims to investigate the feasibility of TDM in patients receiving either axitinib or cabozantinib for the treatment of renal-cell carcinoma with the main objective to improve severe tyrosine kinase inhibitor associated toxicity. Additionally, the feasibility of volumetric absorptive microsampling (VAMS), a novel minimally invasive and easy to handle blood sampling technique, for TDM sample collection is investigated.Exposure-efficacy and/or exposure-toxicity relationships have been identified for up to 80% of oral anticancer drugs (OADs). Usually, OADs are administered at fixed doses despite their high interindividual pharmacokinetic variability resulting in large differences in drug exposure. Consequently, a substantial proportion of patients receive a suboptimal dose. Therapeutic Drug Monitoring (TDM), i.e., dosing based on measured drug concentrations, may be used to improve treatment outcomes. The prospective, multicenter, non-interventional ON-TARGET study (DRKS00025325) aims to investigate the potential of routine TDM to reduce adverse drug reactions in renal cell carcinoma patients receiving axitinib or cabozantinib. Furthermore, the feasibility of using volumetric absorptive microsampling (VAMS), a minimally invasive and easy to handle blood sampling technique, for sample collection is examined. During routine visits, blood samples are collected and sent to bioanalytical laboratories. Venous and VAMS blood samples are collected in the first study phase to facilitate home-based capillary blood sampling in the second study phase. Within one week, the drug plasma concentrations are measured, interpreted, and reported back to the physician. Patients report their drug intake and toxicity using PRO-CTCAE-based questionnaires in dedicated diaries. Ultimately, the ON-TARGET study aims to develop a nationwide infrastructure for TDM for oral anticancer drugs.
Highlights
The development of targeted oral anticancer drugs has significantly improved the number of treatment options, and the prognosis for many tumor entities
We previously identified a lack of experience and a missing infrastructure as an obstacle to the implementation of Therapeutic Drug Monitoring (TDM) for oral anticancer drugs as part of clinical routine [3]
Measured drug concentration is within the interquartile range (IQR) (A): The measured concentration is in the xth (25th–75th) percentile of the concentrations that can be expected for axitinib/cabozantinib, considering the dosing regimen and relevant covariates of the patient
Summary
The development of targeted oral anticancer drugs has significantly improved the number of treatment options, and the prognosis for many tumor entities. The route of administration has changed from intravenous to oral This comes with several advantages, such as reduced patient burden due to venipuncture as well as reduction of healthcare costs and a higher flexibility for the patients, as they have to visit their treatment center less often. Even though exposure-response or exposure-toxicity relationships have been identified for up to 80% of the compounds [3], dosing still mostly follows a “onedose-fits-all” approach. This fixed dosing results in a significant risk for patients to receive suboptimal (i.e., too high or too low) doses [3,4,5]. To prevent therapeutic failure, selecting optimal individual drug doses is crucial
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