Retrospective study of the impact of pharmacogenetic variants on paclitaxel toxicity and survival in patients with ovarian cancer

Autor: 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
Přispěvatelé: 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
Rok vydání: 2010
Předmět:
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
Zdroj: 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/s00228-011-1007-6
ISSN: 1432-1041
0031-6970
DOI: 10.1007/s00228-011-1007-6⟩
Popis: 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.
Databáze: OpenAIRE
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