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,

doi:10.3390/cancers13246281

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Developing a Nationwide Infrastructure for Therapeutic Drug Monitoring of Targeted Oral Anticancer Drugs: The ON-TARGET Study Protocol

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³,

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Stefanie L. Groenland

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¹⁶,

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^1,* and for the ON-TARGET Study Consortium^†

Department of Clinical Pharmacy and Biochemistry, Institute of Pharmacy, Freie Universität Berlin, 12169 Berlin, Germany

Graduate Research Training Program PharMetrX, 12169 Berlin, Germany

Department of Clinical Pharmacy, Institute of Pharmacy, University of Bonn, 53121 Bonn, Germany

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Institute of Pharmacy and Food Chemistry, Julius-Maximilians-Universität Würzburg, 97074 Würzburg, Germany

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Department of Pharmaceutical and Medical Chemistry, Clinical Pharmacy, University of Muenster, 48149 Muenster, Germany

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The Netherlands Cancer Institute, Department of Clinical Pharmacology, Division of Medical Oncology, 1066 CX Amsterdam, The Netherlands

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The Netherlands Cancer Institute, Department of Pharmacy & Pharmacology, 1066 CX Amsterdam, The Netherlands

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Department of Clinical Pharmacy, University Medical Center, Utrecht University, 3584 CX Utrecht, The Netherlands

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Department of Pharmacology, Princess Máxima Center for Pediatric Oncology, 3584 CX Utrecht, The Netherlands

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Onkologie UnterEms, 26789 Leer, Germany

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Onkologische Schwerpunktpraxis Heidelberg, 69115 Heidelberg, Germany

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Klinik für Hämatologie, Onkologie, und Palliativmedizin, Klinikum Stuttgart, 70174 Stuttgart, Germany

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Cantonal Hospital St. Gallen, Department of Medical Oncology & Hematology, CH-9000 St. Gallen, Switzerland

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Praxis und Tagesklinik, Prof. Dr. Helmut Oettle und Prof. Dr. Dr. Frank Mayer, 88045 Friedrichshafen, Germany

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Department I of Pharmacology, Faculty of Medicine and University Hospital Cologne, Center for Pharmacology, University of Cologne, 50923 Cologne, Germany

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German Heart Center Munich, Technical University Munich, Institute of Laboratory Medicine, 80636 Munich, Germany

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^†

There are more individuals involved on the ON-TARGET study consortium. The authors named here have contributed a substantial amount of work and should represent the whole study consortium.

Academic Editor: Birandra K. Sinha

Cancers 2021, 13(24), 6281; https://doi.org/10.3390/cancers13246281

Received: 10 November 2021 / Revised: 10 December 2021 / Accepted: 12 December 2021 / Published: 14 December 2021

(This article belongs to the Special Issue Therapeutic Monitoring of Anti-cancer Agents)

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Relationships 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.

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), 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. View Full-Text

Keywords: therapeutic drug monitoring; oral anticancer drugs; renal cell carcinoma; volumetric absorptive microsampling

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MDPI and ACS Style

Mc Laughlin, A.M.; Schmulenson, E.; Teplytska, O.; Zimmermann, S.; Opitz, P.; Groenland, S.L.; Huitema, A.D.R.; Steeghs, N.; Müller, L.; Fuxius, S.; Illerhaus, G.; Joerger, M.; Mayer, F.; Fuhr, U.; Holdenrieder, S.; Hempel, G.; Scherf-Clavel, O.; Jaehde, U.; Kloft, C.; for the ON-TARGET Study Consortium. Developing a Nationwide Infrastructure for Therapeutic Drug Monitoring of Targeted Oral Anticancer Drugs: The ON-TARGET Study Protocol. Cancers 2021, 13, 6281. https://doi.org/10.3390/cancers13246281

AMA Style

Mc Laughlin AM, Schmulenson E, Teplytska O, Zimmermann S, Opitz P, Groenland SL, Huitema ADR, Steeghs N, Müller L, Fuxius S, Illerhaus G, Joerger M, Mayer F, Fuhr U, Holdenrieder S, Hempel G, Scherf-Clavel O, Jaehde U, Kloft C, for the ON-TARGET Study Consortium. Developing a Nationwide Infrastructure for Therapeutic Drug Monitoring of Targeted Oral Anticancer Drugs: The ON-TARGET Study Protocol. Cancers. 2021; 13(24):6281. https://doi.org/10.3390/cancers13246281

Chicago/Turabian Style

Mc Laughlin, Anna M., Eduard Schmulenson, Olga Teplytska, Sebastian Zimmermann, Patrick Opitz, Stefanie L. Groenland, Alwin D.R. Huitema, Neeltje Steeghs, Lothar Müller, Stefan Fuxius, Gerald Illerhaus, Markus Joerger, Frank Mayer, Uwe Fuhr, Stefan Holdenrieder, Georg Hempel, Oliver Scherf-Clavel, Ulrich Jaehde, Charlotte Kloft, and for the ON-TARGET Study Consortium. 2021. "Developing a Nationwide Infrastructure for Therapeutic Drug Monitoring of Targeted Oral Anticancer Drugs: The ON-TARGET Study Protocol" Cancers 13, no. 24: 6281. https://doi.org/10.3390/cancers13246281

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