Therapeutic Drug Monitoring of Oral Anticancer Drugs: The Dutch Pharmacology Oncology Group-Therapeutic Drug Monitoring Protocol for a Prospective Study

Stefanie L. Groenland; Ruben A.G. Van Eerden; Remy B. Verheijen; Stijn L.W. Koolen; Dirk Jan A.R. Moes; Ingrid M.E. Desar; Anna K.L. Reyners; Hans J. Gelderblom; Nielka P. Van Erp; Ron H.J. Mathijssen; Alwin D.R. Huitema; Neeltje Steeghs

doi:10.1097/ftd.0000000000000654

Therapeutic Drug Monitoring of Oral Anticancer Drugs: The Dutch Pharmacology Oncology Group-Therapeutic Drug Monitoring Protocol for a Prospective Study

Stefanie L. Groenland^*, Ruben A.G. Van Eerden, Remy B. Verheijen, Stijn L.W. Koolen, Dirk Jan A.R. Moes, Ingrid M.E. Desar, Anna K.L. Reyners, Hans J. Gelderblom, Nielka P. Van Erp, Ron H.J. Mathijssen, Alwin D.R. Huitema, Neeltje Steeghs

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

35 Citations (Scopus)

Abstract

Background: Oral anticancer drugs show a high interpatient variability in pharmacokinetics (PK), leading to large differences in drug exposure. For many of these drugs, exposure has been linked to efficacy and toxicity. Despite this knowledge, these drugs are still administered in a one-size-fits-all approach. Consequently, individual patients have a high probability to be either underdosed, which can lead to decreased antitumor efficacy, or overdosed, which could potentially result in increased toxicity. Therapeutic drug monitoring (TDM), personalized dosing based on measured drug levels, could be used to circumvent underdosing and overdosing and thereby optimize treatment outcomes. Methods: In this prospective clinical study (www.trialregister.nl; NL6695), the feasibility, tolerability, and efficacy of TDM of oral anticancer drugs will be evaluated. In total, at least 600 patients will be included for (at least) 23 different compounds. Patients starting regular treatment with one of these compounds at the approved standard dose can be included. PK sampling will be performed at 4, 8, and 12 weeks after the start of treatment and every 12 weeks thereafter. Drug concentrations will be measured, and trough concentrations (C_min) will be calculated. In cases where C_min falls below the predefined target and acceptable toxicity, a PK-guided intervention will be recommended. This could include emphasizing compliance, adapting concomitant medication (due to drug-drug interactions), instructing to take the drug concomitant with food, splitting intake moments, or recommending a dose increase.Discussion:Despite a strong rationale for the use of TDM for oral anticancer drugs, this is currently not yet widely adopted in routine patient care. This prospective study will be a valuable contribution to demonstrate the additional value of dose optimization on treatment outcome for these drugs.

Original language	English
Pages (from-to)	561-567
Number of pages	7
Journal	Therapeutic Drug Monitoring
Volume	41
Issue number	5
DOIs	https://doi.org/10.1097/ftd.0000000000000654
Publication status	Published - 1 Oct 2019

Bibliographical note

Funding Information:
Financial support for this study was received from Novartis, Pfizer, and Roche (unrestricted research grants). They had no role in the design of the study, the collection, analysis, and interpretation of the data, nor did they have any further roles in the analyses and reporting of the results. No material or other support was received for this study.

Publisher Copyright:
© 2019 Wolters Kluwer Health, Inc. All rights reserved.

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Groenland, S. L., Van Eerden, R. A. G., Verheijen, R. B., Koolen, S. L. W., Moes, D. J. A. R., Desar, I. M. E., Reyners, A. K. L., Gelderblom, H. J., Van Erp, N. P., Mathijssen, R. H. J., Huitema, A. D. R., & Steeghs, N. (2019). Therapeutic Drug Monitoring of Oral Anticancer Drugs: The Dutch Pharmacology Oncology Group-Therapeutic Drug Monitoring Protocol for a Prospective Study. Therapeutic Drug Monitoring, 41(5), 561-567. https://doi.org/10.1097/ftd.0000000000000654

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title = "Therapeutic Drug Monitoring of Oral Anticancer Drugs: The Dutch Pharmacology Oncology Group-Therapeutic Drug Monitoring Protocol for a Prospective Study",

abstract = "Background: Oral anticancer drugs show a high interpatient variability in pharmacokinetics (PK), leading to large differences in drug exposure. For many of these drugs, exposure has been linked to efficacy and toxicity. Despite this knowledge, these drugs are still administered in a one-size-fits-all approach. Consequently, individual patients have a high probability to be either underdosed, which can lead to decreased antitumor efficacy, or overdosed, which could potentially result in increased toxicity. Therapeutic drug monitoring (TDM), personalized dosing based on measured drug levels, could be used to circumvent underdosing and overdosing and thereby optimize treatment outcomes. Methods: In this prospective clinical study (www.trialregister.nl; NL6695), the feasibility, tolerability, and efficacy of TDM of oral anticancer drugs will be evaluated. In total, at least 600 patients will be included for (at least) 23 different compounds. Patients starting regular treatment with one of these compounds at the approved standard dose can be included. PK sampling will be performed at 4, 8, and 12 weeks after the start of treatment and every 12 weeks thereafter. Drug concentrations will be measured, and trough concentrations (Cmin) will be calculated. In cases where Cmin falls below the predefined target and acceptable toxicity, a PK-guided intervention will be recommended. This could include emphasizing compliance, adapting concomitant medication (due to drug-drug interactions), instructing to take the drug concomitant with food, splitting intake moments, or recommending a dose increase.Discussion:Despite a strong rationale for the use of TDM for oral anticancer drugs, this is currently not yet widely adopted in routine patient care. This prospective study will be a valuable contribution to demonstrate the additional value of dose optimization on treatment outcome for these drugs.",

author = "Groenland, {Stefanie L.} and {Van Eerden}, {Ruben A.G.} and Verheijen, {Remy B.} and Koolen, {Stijn L.W.} and Moes, {Dirk Jan A.R.} and Desar, {Ingrid M.E.} and Reyners, {Anna K.L.} and Gelderblom, {Hans J.} and {Van Erp}, {Nielka P.} and Mathijssen, {Ron H.J.} and Huitema, {Alwin D.R.} and Neeltje Steeghs",

note = "Funding Information: Financial support for this study was received from Novartis, Pfizer, and Roche (unrestricted research grants). They had no role in the design of the study, the collection, analysis, and interpretation of the data, nor did they have any further roles in the analyses and reporting of the results. No material or other support was received for this study. Publisher Copyright: {\textcopyright} 2019 Wolters Kluwer Health, Inc. All rights reserved.",

year = "2019",

month = oct,

day = "1",

doi = "10.1097/ftd.0000000000000654",

language = "English",

volume = "41",

pages = "561--567",

journal = "Therapeutic Drug Monitoring",

issn = "0163-4356",

publisher = "Lippincott Williams & Wilkins",

number = "5",

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Groenland, SL, Van Eerden, RAG, Verheijen, RB, Koolen, SLW, Moes, DJAR, Desar, IME, Reyners, AKL, Gelderblom, HJ, Van Erp, NP, Mathijssen, RHJ, Huitema, ADR & Steeghs, N 2019, 'Therapeutic Drug Monitoring of Oral Anticancer Drugs: The Dutch Pharmacology Oncology Group-Therapeutic Drug Monitoring Protocol for a Prospective Study', Therapeutic Drug Monitoring, vol. 41, no. 5, pp. 561-567. https://doi.org/10.1097/ftd.0000000000000654

Therapeutic Drug Monitoring of Oral Anticancer Drugs: The Dutch Pharmacology Oncology Group-Therapeutic Drug Monitoring Protocol for a Prospective Study. / Groenland, Stefanie L.; Van Eerden, Ruben A.G.; Verheijen, Remy B. et al.
In: Therapeutic Drug Monitoring, Vol. 41, No. 5, 01.10.2019, p. 561-567.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - Therapeutic Drug Monitoring of Oral Anticancer Drugs

T2 - The Dutch Pharmacology Oncology Group-Therapeutic Drug Monitoring Protocol for a Prospective Study

AU - Groenland, Stefanie L.

AU - Van Eerden, Ruben A.G.

AU - Verheijen, Remy B.

AU - Koolen, Stijn L.W.

AU - Moes, Dirk Jan A.R.

AU - Desar, Ingrid M.E.

AU - Reyners, Anna K.L.

AU - Gelderblom, Hans J.

AU - Van Erp, Nielka P.

AU - Mathijssen, Ron H.J.

AU - Huitema, Alwin D.R.

AU - Steeghs, Neeltje

N1 - Funding Information: Financial support for this study was received from Novartis, Pfizer, and Roche (unrestricted research grants). They had no role in the design of the study, the collection, analysis, and interpretation of the data, nor did they have any further roles in the analyses and reporting of the results. No material or other support was received for this study. Publisher Copyright: © 2019 Wolters Kluwer Health, Inc. All rights reserved.

PY - 2019/10/1

Y1 - 2019/10/1

N2 - Background: Oral anticancer drugs show a high interpatient variability in pharmacokinetics (PK), leading to large differences in drug exposure. For many of these drugs, exposure has been linked to efficacy and toxicity. Despite this knowledge, these drugs are still administered in a one-size-fits-all approach. Consequently, individual patients have a high probability to be either underdosed, which can lead to decreased antitumor efficacy, or overdosed, which could potentially result in increased toxicity. Therapeutic drug monitoring (TDM), personalized dosing based on measured drug levels, could be used to circumvent underdosing and overdosing and thereby optimize treatment outcomes. Methods: In this prospective clinical study (www.trialregister.nl; NL6695), the feasibility, tolerability, and efficacy of TDM of oral anticancer drugs will be evaluated. In total, at least 600 patients will be included for (at least) 23 different compounds. Patients starting regular treatment with one of these compounds at the approved standard dose can be included. PK sampling will be performed at 4, 8, and 12 weeks after the start of treatment and every 12 weeks thereafter. Drug concentrations will be measured, and trough concentrations (Cmin) will be calculated. In cases where Cmin falls below the predefined target and acceptable toxicity, a PK-guided intervention will be recommended. This could include emphasizing compliance, adapting concomitant medication (due to drug-drug interactions), instructing to take the drug concomitant with food, splitting intake moments, or recommending a dose increase.Discussion:Despite a strong rationale for the use of TDM for oral anticancer drugs, this is currently not yet widely adopted in routine patient care. This prospective study will be a valuable contribution to demonstrate the additional value of dose optimization on treatment outcome for these drugs.

AB - Background: Oral anticancer drugs show a high interpatient variability in pharmacokinetics (PK), leading to large differences in drug exposure. For many of these drugs, exposure has been linked to efficacy and toxicity. Despite this knowledge, these drugs are still administered in a one-size-fits-all approach. Consequently, individual patients have a high probability to be either underdosed, which can lead to decreased antitumor efficacy, or overdosed, which could potentially result in increased toxicity. Therapeutic drug monitoring (TDM), personalized dosing based on measured drug levels, could be used to circumvent underdosing and overdosing and thereby optimize treatment outcomes. Methods: In this prospective clinical study (www.trialregister.nl; NL6695), the feasibility, tolerability, and efficacy of TDM of oral anticancer drugs will be evaluated. In total, at least 600 patients will be included for (at least) 23 different compounds. Patients starting regular treatment with one of these compounds at the approved standard dose can be included. PK sampling will be performed at 4, 8, and 12 weeks after the start of treatment and every 12 weeks thereafter. Drug concentrations will be measured, and trough concentrations (Cmin) will be calculated. In cases where Cmin falls below the predefined target and acceptable toxicity, a PK-guided intervention will be recommended. This could include emphasizing compliance, adapting concomitant medication (due to drug-drug interactions), instructing to take the drug concomitant with food, splitting intake moments, or recommending a dose increase.Discussion:Despite a strong rationale for the use of TDM for oral anticancer drugs, this is currently not yet widely adopted in routine patient care. This prospective study will be a valuable contribution to demonstrate the additional value of dose optimization on treatment outcome for these drugs.

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U2 - 10.1097/ftd.0000000000000654

DO - 10.1097/ftd.0000000000000654

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C2 - 31568233

SN - 0163-4356

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JO - Therapeutic Drug Monitoring

JF - Therapeutic Drug Monitoring

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ER -

Therapeutic Drug Monitoring of Oral Anticancer Drugs: The Dutch Pharmacology Oncology Group-Therapeutic Drug Monitoring Protocol for a Prospective Study

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