ABCB1 and ERCC1 gene polymorphisms are associated with nephro- and hepatotoxicity to carboplatin/paclitaxel-based chemotherapy in patients with gynecologic cancers.
Background: Paclitaxel/carboplatin combination is the standard chemotherapeutic protocol for gynecologic cancers, but severe toxicities may compromise treatment. There is great inter-individual variability regarding the incidence and severity of toxicities, which may be due to single-nucleotide poly...
| Publicado en: | European Journal of Clinical Pharmacology Vol. 76; no. 10; pp. 1401 - 1409 |
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| Autores principales: | , , , , |
| Formato: | research tables/charts Journal Article |
| Publicado: |
Springer Nature
Oct2020
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=145654892&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 145654892 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00316970 NP9 jtl: European Journal of Clinical Pharmacology issn: 00316970 maglogo: N pubinfo: dt: Oct2020 vid: 76 iid: 10 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 145654892 144438404 145654892 145654892 10.1007/s00228-020-02934-9 145654892 ppf: 1401 ppct: 8 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: ABCB1 and ERCC1 gene polymorphisms are associated with nephro- and hepatotoxicity to carboplatin/paclitaxel-based chemotherapy in patients with gynecologic cancers. aug: au: da Costa Junior, Luiz Carlos de Castro, Clarissa Lourenço Freitas-Alves, Daniely Regina Vianna-Jorge, Rosane Santos, Paulo Caleb Júnior Lima affil: Department of Pharmacology, Escola Paulista de Medicina (EPM), Universidade Federal de São Paulo (Unifesp), Rua Três de Maio, nº 100, 4° andar, Infar, Vila Clementino, 04044-020, São Paulo, SP, Brazil sug: subj: Genital Neoplasms, Female Drug Therapy Carboplatin Adverse Effects Paclitaxel Adverse Effects Polymorphism, Genetic Nephrotoxicity Risk Factors Hepatotoxicity Risk Factors Human Incidence Genotype Polymerase Chain Reaction Methods Odds Ratio Confidence Intervals Diabetic Patients Nausea Risk Factors Muscle Pain Risk Factors ab: Background: Paclitaxel/carboplatin combination is the standard chemotherapeutic protocol for gynecologic cancers, but severe toxicities may compromise treatment. There is great inter-individual variability regarding the incidence and severity of toxicities, which may be due to single-nucleotide polymorphisms (SNPs) affecting drug disposition or cellular sensitivity. Here we investigate the impact of selected SNPs in ERCC1, ABCB1, CYP2C8, and CYP3A5 genes on the incidence of severe toxicities, including nephro- and hepatotoxicity. Methods: A cohort of 507 gynecological cancer patients receiving paclitaxel/carboplatin was recruited at the Brazilian National Cancer Institute (INCA-Brazil). Clinical data were obtained during routine consultations or from electronic medical records. Toxicities were graded according to the Common Terminology Criteria for Adverse Events (CTCAE 5.0). Genotyping was performed using real-time PCR. Results: ABCB1 c.1236C>T was associated with moderate-to-severe (grades 2–4) nephrotoxicity (ORadjusted 2.40; 95% CI 1.39–4.15), even after adjustment for age (≥ 65) and diabetes. The risk association between ABCB1 c.1236C>T and moderate-to-severe nephrotoxicity following paclitaxel/carboplatin chemotherapy was also present among non-diabetic patients (ORadjusted 2.16; 95% CI 1.22–3.82). ERCC1 c.118C>T was the only individual variable associated with an increased risk for moderate-to-severe (grades 2–4) hepatotoxicity (OR 3.71; 95% CI 1.08–12.77), severe nausea (OR 4.18; 95% CI 1.59–10.95), and severe myalgia (OR 1.95; 95% CI 1.12–3.40). Conclusions: ABCB1 c.1236C>T and ERCC1 c.118C>T might serve as potential biomarkers for the risk of moderate-to-severe toxicities to carboplatin/paclitaxel chemotherapy of gynecological cancers. pubtype: Academic Journal doctype: research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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