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- Title
Association of the hOCT1/ABCB1 genotype with efficacy and tolerability of imatinib in patients affected by chronic myeloid leukemia.
- Authors
Galeotti, Laura; Ceccherini, Francesco; Domingo, Dario; Laurino, Marco; Polillo, Marialuisa; Di Paolo, Antonello; Baratè, Claudia; Fava, Carmen; D'Avolio, Antonio; Cervetti, Giulia; Guerrini, Francesca; Fontanelli, Giulia; Ciabatti, Elena; Grassi, Susanna; Arrigoni, Elena; Danesi, Romano; Petrini, Mario; Cornolti, Fulvio; Saglio, Giuseppe; Galimberti, Sara
- Abstract
<bold>Purpose: </bold>The present study was aimed at investigating whether imatinib pharmacogenetics is related to its pharmacodynamics in patients affected by chronic myeloid leukemia.<bold>Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusions: </bold>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.
- Subjects
TREATMENT of chronic myeloid leukemia; CHRONIC myeloid leukemia; IMATINIB; ORGANIC cation transporters; DRUG efficacy; DRUG toxicity; SINGLE nucleotide polymorphisms; PATIENTS; ANTINEOPLASTIC agents; EDEMA; FACTOR analysis; GENETIC polymorphisms; GLYCOPROTEINS; HUMAN reproduction; PHARMACOGENOMICS; PROGNOSIS; PROTEINS; MUSCLE cramps; GENOTYPES
- Publication
Cancer Chemotherapy & Pharmacology, 2017, Vol 79, Issue 4, p767
- ISSN
0344-5704
- Publication type
journal article
- DOI
10.1007/s00280-017-3271-3