ABCB1 and ABCC2 genetic polymorphism as risk factors for neutropenia in esophageal cancer patients treated with docetaxel, cisplatin, and 5-fluorouracil chemotherapy

Autor: Takashi Kojima, Satoshi Fujii, Hiroyuki Daiko, Hisanaga Nomura, Tomonori Yano, Toshikatsu Kawasaki, Ken Demachi, Nobuo Mochizuki, Daiki Tsuji, Haruki Matsuzawa, Kunihiko Itoh
Rok vydání: 2020
Předmět:
Male
0301 basic medicine
Cancer Research
Esophageal Neoplasms
medicine.medical_treatment
Docetaxel
Toxicology
Gastroenterology
0302 clinical medicine
Risk Factors
hemic and lymphatic diseases
Antineoplastic Combined Chemotherapy Protocols
Pharmacology (medical)
Middle Aged
Esophageal cancer
Prognosis
Chemotherapy regimen
Multidrug Resistance-Associated Protein 2
Survival Rate
Oncology
Fluorouracil
030220 oncology & carcinogenesis
Absolute neutrophil count
Female
Multidrug Resistance-Associated Proteins
medicine.drug
Adult
medicine.medical_specialty
ATP Binding Cassette Transporter
Subfamily B
Neutropenia
Genotype
03 medical and health sciences
Internal medicine
Biomarkers
Tumor
medicine
Humans
Aged
Retrospective Studies
Pharmacology
Cisplatin
Chemotherapy
Polymorphism
Genetic
business.industry
medicine.disease
030104 developmental biology
business
Follow-Up Studies
Zdroj: Cancer Chemotherapy and Pharmacology. 86:315-324
ISSN: 1432-0843
0344-5704
DOI: 10.1007/s00280-020-04118-9
Popis: The combination of docetaxel, cisplatin and 5-fluorouracil (DCF) is a newly developed chemotherapy regimen for esophageal cancer. Severe neutropenia is dose-limiting toxicity of docetaxel and it is well known to be frequently occurred during DCF chemotherapy. This study aimed to investigate the relationship between severe neutropenia and genetic polymorphisms in patients treated with preoperative DCF chemotherapy. A total of 158 patients were investigated for their absolute neutrophil count (ANC) within the first cycle of DCF chemotherapy at the National Cancer Center (NCC) Hospital East. DNA samples obtained from the NCC Biobank Registry were used for the analysis of nine genetic polymorphisms related to docetaxel pharmacokinetics. These genotypes were evaluated for their association with severe neutropenia, and further their risk factors were examined using a multivariate logistic regression. A total 81 (51.3%) patients developed severe neutropenia. Multivariate analysis revealed that age (OR 1.054; CI 1.008–1.102, P = 0.022), baseline ANC (OR 1.019; CI 1.002–1.037, P = 0.030), ABCB1 3435C>T (OR 2.191; CI 1.087–4.417, P = 0.028) and ABCC2 *+9383C>G (OR 2.342; CI 1.108–4.948, P = 0.026) were significant risk factors for severe neutropenia development. The results from this study showed that age, ANC, ABCB1 3435C>T, and ABCC2 *+9383 G>C increased the incidence of severe neutropenia with the number of identified risk factors. In addition to age and baseline ANC, ABCB1 3435C>T and ABCC2 *+9383C>G were identified as independent predictors for severe neutropenia in esophageal cancer patients treated with DCF chemotherapy.
Databáze: OpenAIRE
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