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Impact of CYP3A5(*)3 and CYP2C8-HapC on Paclitaxel/Carboplatin-Induced Myelosuppression in Patients with Ovarian Cancer
Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.ORCID iD: 0000-0003-4450-0333
Karolinska University of Hospital.
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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 andlt; 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
Elsevier, 2011. Vol. 100, no 10, 4205-4209 p.
Keyword [en]
CYP enzymes, pharmacogenetics, toxicity, polymorphism, drug metabolizing enzymes, cancer chemotherapy
National Category
Pharmaceutical Sciences
Identifiers
URN: urn:nbn:se:liu:diva-71784DOI: 10.1002/jps.22680ISI: 000295733800011PubMedID: 21702053Scopus ID: 2-s2.0-80052240853OAI: oai:DiVA.org:liu-71784DiVA: diva2:453942
Note

Funding Agencies|Swedish Cancer Society||Swedish Research Council||European Commission|CHEMORES LSHC-CT-2007-037665|Ostergotland County Council||

Available from: 2011-11-04 Created: 2011-11-04 Last updated: 2017-04-28Bibliographically approved

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Green, HenrikJakobsen Falk, IngridPeterson, Curt

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