Genetic Risk Factors Associated With Antiemetic Efficacy of Palonosetron, Aprepitant, and Dexamethasone in Japanese Breast Cancer Patients Treated With Anthracycline-based Chemotherapy

Clin Breast Cancer. 2018 Apr;18(2):e157-e165. doi: 10.1016/j.clbc.2017.05.013. Epub 2017 Jun 29.

Abstract

Introduction: Breast cancer patients often receive anthracycline-based chemotherapy, and chemotherapy-induced nausea and vomiting (CINV) remains one of the most uncomfortable and distressing adverse reactions. Poor control of CINV reduces the relative dose intensity of chemotherapy agents, which has been associated with poor clinical outcomes and shorter survival. The aim of the present study was to identify genetic risk factors associated with anthracycline-based CINV.

Patients and methods: We evaluated CINV attributable to anthracycline-based chemotherapy in Japanese breast cancer patients treated with an antiemetic regimen that included palonosetron, aprepitant, and dexamethasone. Furthermore, we investigated the associations between CINV and single nucleotide polymorphisms in 6 candidate genes.

Results: Emesis episodes were rarely observed in the 125 patients included in the present survey (7.2%; n = 9); however, significant nausea occurred in more than one half of the patients (52.8%; n = 66). In particular, acute significant nausea was not effectively controlled. Multivariate logistic regression analysis revealed that the ABCG2 (rs2231142) AA genotype is significantly associated with acute significant nausea (odds ratio, 4.87; 95% confidence interval, 1.01-23.60; P = .049).

Conclusion: The findings of the present study provide significant insights for developing personalized antiemetic strategies for breast cancer patients receiving anthracycline-based chemotherapy.

Keywords: ABCG2; Antiemetic agents; Chemotherapy-induced nausea and vomiting; Genetic factors; Single nucleotide polymorphism.

Publication types

  • Multicenter Study
  • Observational Study

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily G, Member 2 / genetics*
  • Adult
  • Anthracyclines / adverse effects
  • Antibiotics, Antineoplastic / adverse effects*
  • Antiemetics / therapeutic use*
  • Aprepitant / therapeutic use
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics
  • Dexamethasone / therapeutic use
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Middle Aged
  • Nausea / chemically induced
  • Nausea / drug therapy
  • Nausea / epidemiology
  • Nausea / genetics*
  • Neoplasm Proteins / genetics*
  • Odds Ratio
  • Palonosetron / therapeutic use
  • Polymorphism, Single Nucleotide
  • Prospective Studies
  • Risk Factors
  • Treatment Outcome
  • Vomiting / chemically induced
  • Vomiting / drug therapy
  • Vomiting / epidemiology
  • Vomiting / genetics

Substances

  • ABCG2 protein, human
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • Anthracyclines
  • Antibiotics, Antineoplastic
  • Antiemetics
  • Neoplasm Proteins
  • Aprepitant
  • Palonosetron
  • Dexamethasone