Retrospective study of the impact of pharmacogenetic variants on paclitaxel toxicity and survival in patients with ovarian cancer
| العنوان: | Retrospective study of the impact of pharmacogenetic variants on paclitaxel toxicity and survival in patients with ovarian cancer |
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| المؤلفون: | Per Damkier, Charlotte Brasch-Andersen, Kim Brøsen, Andreas du Bois, Carsten Peterson, Mansoor Raza Mirza, Jørn Herrstedt, Henrik Gréen, Berit Hølund, Werner Vach, Troels K Bergmann |
| المساهمون: | Clinical Pharmacology, Institute of Public Health, University of Southern Denmark (SDU), Clinical Pharmacology, Department of Medical and Health Sciences, Linköping University (LIU), Department of Clinical Chemistry and Pharmacology, Odense University Hospital, Department of Oncology, Department of Pathology, Gynecology & Gynecological Oncology, Dr. Horst Schmidt Clinic, Clinical Epidemiology, Institute of Medical Biometry and Medical Informatics, Freiburg University Medical Center |
| المصدر: | European Journal of Clinical Pharmacology European Journal of Clinical Pharmacology, Springer Verlag, 2011, 67 (7), pp.693-700. ⟨10.1007/s00228-011-1007-6⟩ Bergmann, T K, Gréen, H, Andersen, C B, Mirza, M R, Herrstedt, J, Hølund, B, du Bois, A, Damkier, P, Vach, W, Brøsen, K & Peterson, C 2011, ' Retrospective study of the impact of pharmacogenetic variants on paclitaxel toxicity and survival in patients with ovarian cancer ', European Journal of Clinical Pharmacology, vol. 67, no. 7, pp. 693-700 . https://doi.org/10.1007/s00228-011-1007-6Test |
| سنة النشر: | 2010 |
| مصطلحات موضوعية: | Oncology, CYP2C8, chemistry.chemical_compound, 0302 clinical medicine, Pharmacology (medical), ComputingMilieux_MISCELLANEOUS, Ovarian Neoplasms, 0303 health sciences, Leukopenia, ABCB1, General Medicine, Middle Aged, 3. Good health, Treatment Outcome, Paclitaxel, 030220 oncology & carcinogenesis, Toxicity, Female, Aryl Hydrocarbon Hydroxylases, medicine.symptom, Adult, medicine.medical_specialty, Neutropenia, ATP Binding Cassette Transporter, Subfamily B, Genotype, Polymorphism, Single Nucleotide, Cytochrome P-450 CYP2C8, 03 medical and health sciences, Ovarian cancer, Internal medicine, medicine, Humans, ATP Binding Cassette Transporter, Subfamily B, Member 1, Lung cancer, 030304 developmental biology, Aged, Proportional Hazards Models, Retrospective Studies, Pharmacology, business.industry, Cancer, Retrospective cohort study, medicine.disease, Antineoplastic Agents, Phytogenic, Neuropathy, chemistry, Pharmacogenetics, Immunology, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, business |
| الوصف: | Paclitaxel has a broad spectrum of anti-tumor activity and is useful in the treatment of ovarian, breast, and lung cancer. Paclitaxel is metabolized in the liver by CYP2C8 and CYP3A4 and transported by P-glycoprotein. The dose-limiting toxicities are neuropathy and neutropenia, but the interindividual variability in toxicity and also survival is large. The main purpose of this study was to investigate the impact of genetic variants in CYP2C8 and ABCB1 on toxicity and survival.The 182 patients previously treated for ovarian cancer with carboplatin and paclitaxel in either the AGO-OVAR-9 or the NSGO-OC9804 trial in Denmark or Sweden were eligible for this study. Genotyping was carried out on formalin-fixed tissue. The patients' toxicity profiles and survival data were derived from retrospective data. CYP2C8*3, ABCB1 C1236T, G2677T/A, and C3435T were chosen a priori for primary analysis; a host of other variants were entered into an exploratory analysis.Clinical data and tissue were available from a total of 119 patients. Twenty-two single nucleotide polymorphisms (SNPs) in 10 genes were determined. Toxicity registration was available from 710 treatment cycles. In the primary analysis, no statistically significant correlation was found between CYP2C8*3, ABCB1 C1236T, G2677T/A, and C3435T and neutropenia, sensoric neuropathy, and overall survival.CYP2C8*3 and the ABCB1 SNPs C1236T, G2677T/A, and C3435T were not statistically significantly correlated to overall survival, sensoric neuropathy, and neutropenia in 119 patients treated for ovarian cancer with paclitaxel/carboplatin. |
| تدمد: | 1432-1041 0031-6970 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::254514ee5909581e15e96955f7dd9768Test https://pubmed.ncbi.nlm.nih.gov/21327421Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....254514ee5909581e15e96955f7dd9768 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14321041 00316970 |
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