Developing a Nationwide Infrastructure for Therapeutic Drug Monitoring of Targeted Oral Anticancer Drugs: The ON-TARGET Study Protocol
Mc Laughlin, Anna M; Schmulenson, Eduard; Teplytska, Olga; Zimmermann, Sebastian; Opitz, Patrick; Groenland, Stefanie L; Huitema, Alwin D R; Steeghs, Neeltje; Müller, Lothar; Fuxius, Stefan; Illerhaus, Gerald; Joerger, Markus; Mayer, Frank; Fuhr, Uwe; Holdenrieder, Stefan; Hempel, Georg; Scherf-Clavel, Oliver; Jaehde, Ulrich; Kloft, Charlotte; For The On-Target Study Consortium
(2021) Cancers, volume 13, issue 24
(Article)
Abstract
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),
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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.
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Keywords: Oral anticancer drugs, Renal cell carcinoma, Therapeutic drug monitoring, Volumetric absorptive microsampling, Oncology, Cancer Research, Journal Article
ISSN: 2072-6694
Publisher: Multidisciplinary Digital Publishing Institute (MDPI)
Note: Funding Information: Conflicts of Interest: C.K. reports grants from an industry consortium (AbbVie Deutschland GmbH & Co. KG, AstraZeneca Ltd., Boehringer Ingelheim Pharma GmbH & Co. KG, Grünenthal GmbH, F. Hoffmann‐La Roche Ltd., Merck KGaA and Sanofi) for the PharMetrX Graduate Research Train‐ ing program and grants for DDMore within the Innovative Medicines Initiative‐Joint Undertaking. O.S. reports endowed professorship grant (Horphag research Ltd.) and funding for the project ‘In‐ dividualized cancer therapy with kinase inhibitors using drug monitoring–optimization by mini‐ mally invasive at‐home sampling’ (Hector Stiftung II gGmbH). NS reports research grants for the institute from GSK, Merck, Novartis, Pfizer and Roche for the Dutch DPOG‐TDM study, further NS provided consultation or attended advisory boards for AIMM Therapeutics, Boehringer Ingelheim, Ellipses Pharma and NS received research grants for the institute from AB Science, Abbvie, Actuate Funding Information: Funding: This research is financially supported by the Eva Mayr‐Stihl Foundation. Open Access Funding provided by Freie Universität Berlin. Funding Information: This research is financially supported by the Eva Mayr-Stihl Foundation. Open Access Funding provided by Freie Universit?t Berlin. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
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