Moving towards dose individualization of tyrosine kinase inhibitors

Heinz-Josef Klümpen, Caroline F. Samer, Ron H. J. Mathijssen, Jan H. M. Schellens, Howard Gurney

Research output: Contribution to journalReview articleAcademicpeer-review

Abstract

Molecular targeted therapies with tyrosine kinase inhibitors (TKIs) have been a recent breakthrough in cancer treatment. These small molecules are mainly used at a fixed dose ignoring the possible need for dose individualization. Fixed dosing may indeed result in suboptimal treatment or excessive toxicity considering the high inter-individual variability in the pharmacokinetics (PK) of these therapies. The PK, toxicity and efficacy of ten commonly used molecular targeted anti-cancer therapies were reviewed in order to optimize their prescription. A wide interpatient variability in the pharmacokinetics of these small molecules is demonstrated. Moreover associations between certain toxicities and the treatment efficacy have also been demonstrated for some agents, such as erlotinib and skin rash, that may be used as a surrogate marker. Other biomarkers intended to substitute for a clinical endpoint have been described for some TKIs and may be useful for dose individualization. Promising alternatives to fixed dosing were explored such as therapeutic drug monitoring, genotype and phenotype adjusted dosing, and toxicity-adjusted dosing. Prospective studies are needed to validate these methods so that dosing algorithms may be developed in the near future in order to personalize therapeutics to the individual needs of each cancer patient. © 2010 Elsevier Ltd.
Original languageEnglish
Pages (from-to)251-260
JournalCancer Treatment Reviews
Volume37
Issue number4
DOIs
Publication statusPublished - 2011
Externally publishedYes

Cite this

Klümpen, H-J., Samer, C. F., Mathijssen, R. H. J., Schellens, J. H. M., & Gurney, H. (2011). Moving towards dose individualization of tyrosine kinase inhibitors. Cancer Treatment Reviews, 37(4), 251-260. https://doi.org/10.1016/j.ctrv.2010.08.006
Klümpen, Heinz-Josef ; Samer, Caroline F. ; Mathijssen, Ron H. J. ; Schellens, Jan H. M. ; Gurney, Howard. / Moving towards dose individualization of tyrosine kinase inhibitors. In: Cancer Treatment Reviews. 2011 ; Vol. 37, No. 4. pp. 251-260.
@article{b0b74d5bc0174a7293d8a8174b2b2987,
title = "Moving towards dose individualization of tyrosine kinase inhibitors",
abstract = "Molecular targeted therapies with tyrosine kinase inhibitors (TKIs) have been a recent breakthrough in cancer treatment. These small molecules are mainly used at a fixed dose ignoring the possible need for dose individualization. Fixed dosing may indeed result in suboptimal treatment or excessive toxicity considering the high inter-individual variability in the pharmacokinetics (PK) of these therapies. The PK, toxicity and efficacy of ten commonly used molecular targeted anti-cancer therapies were reviewed in order to optimize their prescription. A wide interpatient variability in the pharmacokinetics of these small molecules is demonstrated. Moreover associations between certain toxicities and the treatment efficacy have also been demonstrated for some agents, such as erlotinib and skin rash, that may be used as a surrogate marker. Other biomarkers intended to substitute for a clinical endpoint have been described for some TKIs and may be useful for dose individualization. Promising alternatives to fixed dosing were explored such as therapeutic drug monitoring, genotype and phenotype adjusted dosing, and toxicity-adjusted dosing. Prospective studies are needed to validate these methods so that dosing algorithms may be developed in the near future in order to personalize therapeutics to the individual needs of each cancer patient. {\circledC} 2010 Elsevier Ltd.",
author = "Heinz-Josef Kl{\"u}mpen and Samer, {Caroline F.} and Mathijssen, {Ron H. J.} and Schellens, {Jan H. M.} and Howard Gurney",
year = "2011",
doi = "10.1016/j.ctrv.2010.08.006",
language = "English",
volume = "37",
pages = "251--260",
journal = "Cancer Treatment Reviews",
issn = "0305-7372",
publisher = "W.B. Saunders Ltd",
number = "4",

}

Moving towards dose individualization of tyrosine kinase inhibitors. / Klümpen, Heinz-Josef; Samer, Caroline F.; Mathijssen, Ron H. J.; Schellens, Jan H. M.; Gurney, Howard.

In: Cancer Treatment Reviews, Vol. 37, No. 4, 2011, p. 251-260.

Research output: Contribution to journalReview articleAcademicpeer-review

TY - JOUR

T1 - Moving towards dose individualization of tyrosine kinase inhibitors

AU - Klümpen, Heinz-Josef

AU - Samer, Caroline F.

AU - Mathijssen, Ron H. J.

AU - Schellens, Jan H. M.

AU - Gurney, Howard

PY - 2011

Y1 - 2011

N2 - Molecular targeted therapies with tyrosine kinase inhibitors (TKIs) have been a recent breakthrough in cancer treatment. These small molecules are mainly used at a fixed dose ignoring the possible need for dose individualization. Fixed dosing may indeed result in suboptimal treatment or excessive toxicity considering the high inter-individual variability in the pharmacokinetics (PK) of these therapies. The PK, toxicity and efficacy of ten commonly used molecular targeted anti-cancer therapies were reviewed in order to optimize their prescription. A wide interpatient variability in the pharmacokinetics of these small molecules is demonstrated. Moreover associations between certain toxicities and the treatment efficacy have also been demonstrated for some agents, such as erlotinib and skin rash, that may be used as a surrogate marker. Other biomarkers intended to substitute for a clinical endpoint have been described for some TKIs and may be useful for dose individualization. Promising alternatives to fixed dosing were explored such as therapeutic drug monitoring, genotype and phenotype adjusted dosing, and toxicity-adjusted dosing. Prospective studies are needed to validate these methods so that dosing algorithms may be developed in the near future in order to personalize therapeutics to the individual needs of each cancer patient. © 2010 Elsevier Ltd.

AB - Molecular targeted therapies with tyrosine kinase inhibitors (TKIs) have been a recent breakthrough in cancer treatment. These small molecules are mainly used at a fixed dose ignoring the possible need for dose individualization. Fixed dosing may indeed result in suboptimal treatment or excessive toxicity considering the high inter-individual variability in the pharmacokinetics (PK) of these therapies. The PK, toxicity and efficacy of ten commonly used molecular targeted anti-cancer therapies were reviewed in order to optimize their prescription. A wide interpatient variability in the pharmacokinetics of these small molecules is demonstrated. Moreover associations between certain toxicities and the treatment efficacy have also been demonstrated for some agents, such as erlotinib and skin rash, that may be used as a surrogate marker. Other biomarkers intended to substitute for a clinical endpoint have been described for some TKIs and may be useful for dose individualization. Promising alternatives to fixed dosing were explored such as therapeutic drug monitoring, genotype and phenotype adjusted dosing, and toxicity-adjusted dosing. Prospective studies are needed to validate these methods so that dosing algorithms may be developed in the near future in order to personalize therapeutics to the individual needs of each cancer patient. © 2010 Elsevier Ltd.

UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=79953077853&origin=inward

UR - https://www.ncbi.nlm.nih.gov/pubmed/20833478

U2 - 10.1016/j.ctrv.2010.08.006

DO - 10.1016/j.ctrv.2010.08.006

M3 - Review article

VL - 37

SP - 251

EP - 260

JO - Cancer Treatment Reviews

JF - Cancer Treatment Reviews

SN - 0305-7372

IS - 4

ER -