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Impact of CYP3A5(*)3 and CYP2C8-HapC on Paclitaxel/Carboplatin-Induced Myelosuppression in Patients with Ovarian Cancer
KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
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2011 (English)In: Journal of Pharmaceutical Sciences, ISSN 0022-3549, E-ISSN 1520-6017, Vol. 100, no 10, 4205-4209 p.Article in journal (Refereed) Published
Abstract [en]

The influence of genetic variants on paclitaxel-induced toxicity is of considerable interest for reducing adverse drug reactions. Recently, the genetic variants CYP2C8(*)3, CYP2C8-HapC, and CYP3A5(*)3 were associated with paclitaxel-induced neurotoxicity. We, therefore, investigated the impact of CYP2C8-HapC and CYP3A5(*)3 on paclitaxel/carboplatin-induced myelosuppression and neurotoxicity. Thirty-three patients from a prospective pharmacokinetics study were genotyped using pyrosequencing. Patients with variant alleles of CYP2C8-HapC were found to have significantly lower nadir values of both leukocytes and neutrophils (p < 0.05) than patients with the wild-type genotype. CYP3A5(*)3/(*)1 patients were shown to have borderline, significantly lower nadir values of leukocytes (p = 0.07) than (*)3/(*)3 patients. Combining the two genotypes resulted in a significant correlation with both leukopenia and neutropenia (p = 0.01). No effect of these genetic variants on neurotoxicity could be shown in this rather small study, but their importance for paclitaxel-induced toxicity could be confirmed.

Place, publisher, year, edition, pages
2011. Vol. 100, no 10, 4205-4209 p.
Keyword [en]
CYP enzymes, pharmacogenetics, toxicity, polymorphism, drug metabolizing enzymes, cancer chemotherapy
National Category
Pharmacology and Toxicology
URN: urn:nbn:se:kth:diva-46856DOI: 10.1002/jps.22680ISI: 000295733800011ScopusID: 2-s2.0-80052240853OAI: diva2:454350
QC 20111107Available from: 2011-11-07 Created: 2011-11-07 Last updated: 2012-01-09Bibliographically approved

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Green, Henrik
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