Trial reportCancer chemotherapy and pharmacology2020
The influence of single-nucleotide polymorphisms on overall survival and toxicity in cabazitaxel-treated patients with metastatic castration-resistant prostate cancer.
Trial report in Cancer chemotherapy and pharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
6 citing papers in PubMed, 6 citations in OpenAlex.
- SLCO1B1 Polymorphisms are Associated with the Susceptibility to Pulmonary Tuberculosis in Chinese Females.Biochemical genetics · 2024Article
- A Metabolomics Approach for Predicting OATP1B-Type Transporter-Mediated Drug-Drug Interaction Liabilities.Pharmaceutics · 2022Article
- APOE gene ɛ4 allele (388C-526C) effects on serum lipids and risk of coronary artery disease in southern Chinese Hakka population.Journal of clinical laboratory analysis · 2021Article
- Long-Term Prostate-Specific Antigen Response on a Low-Dose Cabazitaxel Regimen for Metastatic Castration-Resistant Prostate Cancer: A Case Report.The American journal of case reports · 2021Article
- Genetic Polymorphisms and Pharmacotherapy for Prostate Cancer.JMA journal · 2021Review
- The SNPs rs429358 and rs7412 of APOE gene are association with cerebral infarction but not SNPs rs2306283 and rs4149056 of SLCO1B1 gene in southern Chinese Hakka population.Lipids in health and disease · 2020Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeCabazitaxel, used in patients with metastatic castration-resistant prostate cancer (mCRPC), is associated with adverse events which may require dose reductions or discontinuation of treatment. We investigated the potential association of single-nucleotide polymorphisms (SNPs) in genes encoding drug transporters and drug-metabolizing enzymes with cabazitaxel toxicity, overall survival (OS) and pharmacokinetics (PK).
methodsA total of 128 cabazitaxel-treated mCRPC patients, of whom prospectively collected data on toxicity and OS were available and 24 mCRPC patients with available cabazitaxel PK measurements, were genotyped using genomic DNA obtained from EDTA blood. The SLCO1B1 (388A > G; *1B; rs2306283 and 521 T > C; *5; rs4149056 and haplotype SLCO1B1*15), SLCO1B3 (334 T > G; rs4149117), CYP3A4 (*22; rs35599367), CYP3A5 (*3; rs776746), ABCB1 (3435C > T; rs1045642), and TUBB1 (57 + 87A > C; rs463312) SNPs were tested for their association with clinical and PK parameters by univariate/multivariate logistic regression, log-rank test, or Kruskal-Wallis test.
resultsThe SLCO1B1*15 haplotype was significantly associated with a lower incidence of leukopenia and neutropenia (p = 0.020 and p = 0.028, respectively). Patients harboring a homozygous variant for SLCO1B1*1B experienced higher rate ≥ grade 3 (p = 0.042). None of the SNPs were associated with pharmacokinetics or OS.
conclusionsIn this study, SLCO1B1 (SLCO1B1*15 and SLCO1B1*1B) was associated with cabazitaxel-induced adverse events in mCRPC patients. As the associations were opposite to previous studies in other drugs and contradicted an underlying pharmacokinetic rationale, these findings are likely to be false-positive and would ideally be validated with even larger (pharmacokinetic) cohorts.
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