Impact of CYP3A5(*)3 and CYP2C8-HapC on Paclitaxel/Carboplatin-Induced Myelosuppression in Patients with Ovarian Cancer
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
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
Wiley-Blackwell , 2011. Vol. 100, no 10, 4205-4209 p.
CYP enzymes, pharmacogenetics, toxicity, polymorphism, drug metabolizing enzymes, cancer chemotherapy
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-71784DOI: 10.1002/jps.22680ISI: 000295733800011OAI: oai:DiVA.org:liu-71784DiVA: diva2:453942
Funding Agencies|Swedish Cancer Society||Swedish Research Council||European Commission|CHEMORES LSHC-CT-2007-037665|Ostergotland County Council||2011-11-042011-11-042013-09-03