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Impact of ABCG2 and ABCB1 Polymorphisms on Imatinib Plasmatic Exposure: An Original Work and Meta-Analysis.
Dalle Fratte, Chiara; Polesel, Jerry; Gagno, Sara; Posocco, Bianca; De Mattia, Elena; Roncato, Rossana; Orleni, Marco; Puglisi, Fabio; Guardascione, Michela; Buonadonna, Angela; Toffoli, Giuseppe; Cecchin, Erika.
Affiliation
  • Dalle Fratte C; Experimental and Clinical Pharmacology, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081 Aviano, Italy.
  • Polesel J; Unit of Cancer Epidemiology, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081 Aviano, Italy.
  • Gagno S; Experimental and Clinical Pharmacology, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081 Aviano, Italy.
  • Posocco B; Experimental and Clinical Pharmacology, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081 Aviano, Italy.
  • De Mattia E; Experimental and Clinical Pharmacology, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081 Aviano, Italy.
  • Roncato R; Experimental and Clinical Pharmacology, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081 Aviano, Italy.
  • Orleni M; Experimental and Clinical Pharmacology, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081 Aviano, Italy.
  • Puglisi F; Doctoral School in Pharmacological Sciences, University of Padua, 35131 Padova, Italy.
  • Guardascione M; Department of Medical Oncology, Unit of Medical Oncology and Cancer Prevention, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081 Aviano, Italy.
  • Buonadonna A; Department of Medicine, University of Udine, 33100 Udine, Italy.
  • Toffoli G; Department of Medical Oncology, Unit of Medical Oncology and Cancer Prevention, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081 Aviano, Italy.
  • Cecchin E; Department of Medical Oncology, Unit of Medical Oncology and Cancer Prevention, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081 Aviano, Italy.
Int J Mol Sci ; 24(4)2023 Feb 07.
Article de En | MEDLINE | ID: mdl-36834713
ABSTRACT
Adequate imatinib plasma levels are necessary to guarantee an efficacious and safe treatment in gastrointestinal stromal tumor (GIST) and chronic myeloid leukemia (CML) patients. Imatinib is a substrate of the drug transporters ATP-binding cassette subfamily B member 1 (ABCB1) and ATP-binding cassette subfamily G member 2 (ABCG2) that can affect its plasma concentration. In the present study, the association between three genetic polymorphisms in ABCB1 (rs1045642, rs2032582, rs1128503) and one in ABCG2 (rs2231142) and the imatinib plasma trough concentration (Ctrough) was investigated in 33 GIST patients enrolled in a prospective clinical trial. The results of the study were meta-analyzed with those of other seven studies (including a total of 649 patients) selected from the literature through a systematic review process. The ABCG2 c.421C>A genotype demonstrated, in our cohort of patients, a borderline association with imatinib plasma trough levels that became significant in the meta-analysis. Specifically, homozygous carriers of the ABCG2 c.421 A allele showed higher imatinib plasma Ctrough with respect to the CC/CA carriers (Ctrough, 1463.2 ng/mL AA, vs. 1196.6 ng/mL CC + AC, p = 0.04) in 293 patients eligible for the evaluation of this polymorphism in the meta-analysis. The results remained significant under the additive model. No significant association could be described between ABCB1 polymorphisms and imatinib Ctrough, neither in our cohort nor in the meta-analysis. In conclusion, our results and the available literature studies sustain an association between ABCG2 c.421C>A and imatinib plasma Ctrough in GIST and CML patients.
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Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Sujet principal: Leucémie myéloïde chronique BCR-ABL positive / Tumeurs stromales gastro-intestinales / Antinéoplasiques Type d'étude: Observational_studies / Risk_factors_studies / Systematic_reviews Limites: Humans Langue: En Journal: Int J Mol Sci Année: 2023 Type de document: Article Pays d'affiliation: Italie

Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Sujet principal: Leucémie myéloïde chronique BCR-ABL positive / Tumeurs stromales gastro-intestinales / Antinéoplasiques Type d'étude: Observational_studies / Risk_factors_studies / Systematic_reviews Limites: Humans Langue: En Journal: Int J Mol Sci Année: 2023 Type de document: Article Pays d'affiliation: Italie