Galeotti, L, Ceccherini, F, Domingo, D orcid.org/0000-0001-8276-6779 et al. (17 more authors) (2017) Association of the hOCT1/ABCB1 genotype with efficacy and tolerability of imatinib in patients affected by chronic myeloid leukemia. Cancer Chemotherapy and Pharmacology, 79 (4). pp. 767-773. ISSN 0344-5704
Abstract
Purpose
The present study was aimed at investigating whether imatinib pharmacogenetics is related to its pharmacodynamics in patients affected by chronic myeloid leukemia.
Methods
Through a procedure based on a sequence of classical statistics methods, we investigated the possible relationships between treatment efficacy/tolerability and combinations of time-independent variables as gender and genetic covariates in the form of single nucleotide polymorphisms (SNPs) or combinations thereof. Moreover, since the drug tolerability has a strong incidence on the discontinuation of the therapy, we investigated whether the time of manifestation of the most frequent toxic effects can be related to time-independent patients’ characteristics or not.
Results
We found that a combination of two polymorphisms, namely hOCT1 c.480C>G (rs683369) and ABCB1 c.3435C>T (rs1045642), seems to play the role of predictor for imatinib in both efficacy and toxicity. Furthermore, the time of manifestation of edema toxicity is found to be associated to a combination of gender and ABCB1 c.3435C>T, whereas the time of manifestation of cramp toxicity appears related to gender.
Conclusions
The novelty of this study is dual: the achievement of results that potentially have a significant clinical interest and the demonstration that the adoption of composed covariates may represent a unique tool to study different aspects of the treatment with imatinib.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Keywords: | Imatinib; hOCT1; ABCB1; Complete cytogenetic response; Tolerability; Factor analysis of mixed data |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Engineering & Physical Sciences (Leeds) > School of Mathematics (Leeds) > Statistics (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 10 Jul 2019 10:55 |
Last Modified: | 10 Jul 2019 10:56 |
Status: | Published |
Publisher: | Springer |
Identification Number: | 10.1007/s00280-017-3271-3 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:148357 |