Genetic risk factors for chemotherapy-induced nausea and vomiting in patients with cancer receiving cisplatin-based chemotherapy

  • Mari Yokoi
  • Daiki Tsuji
  • Kenichi Suzuki
  • Yohei Kawasaki
  • Masahiko Nakao
  • Hideaki Ayuhara
  • Yuuki Kogure
  • Kazuhiko Shibata
  • Toshinobu Hayashi
  • Keita Hirai
  • Kazuyuki Inoue
  • Toshihiro Hama
  • Koji Takeda
  • Makoto Nishio
  • Kunihiko Itoh
Original Article

Abstract

Purpose

Younger age and female sex have already been well-known risk factors for chemotherapy-induced nausea and vomiting (CINV), and 30–50% of cancer patients still suffer from CINV. Genetic polymorphisms are suggested to influence antiemetic treatment response.

Methods

This study included a subset of patients previously enrolled in a randomised controlled trial; 156 patients were evaluated. This study aimed to evaluate the role of pharmacogenomic polymorphisms relevant to antiemetic response in patients with cancer receiving cisplatin-based chemotherapy. The study’s efficacy endpoint was the proportion of patients with complete response (CR). The study endpoint was evaluated separately in the acute (CR0–24) and delayed (CR24–120) phases. Thirteen polymorphisms were genotyped, and the association of these genotypes with the efficacy of prophylactic antiemetics was then investigated. Confounding variables for the CR were identified using stepwise multivariate logistic regression analysis. Age and sex were included as independent variables by the forced-entry method, and the stepwise method was used to select the pharmacogenomic factors for inclusion as independent variables.

Results

Multivariate logistic regression analysis revealed that the ERCC1 8092AA (odds ratio [OR] = 11.25; 95% confidence interval [CI] 1.74–72.71; p = 0.011) and female sex (OR = 3.63; 95% CI 1.14–11.58; p = 0.029) were significant predictors of CR0–24. No significant association of CR24–120 with pharmacogenomic polymorphisms was found via multivariate logistic regression analysis.

Conclusions

ERCC1 polymorphism influenced the extent of CINV control in patients receiving cisplatin-based chemotherapy.

Trial registration

Clinical trial information: UMIN 000009335

Keywords

Chemotherapy-induced nausea and vomiting (CINV) ERCC1 polymorphism Cisplatin Granisetron Palonosetron Aprepitant 

Notes

Acknowledgements

We wish to thank all the patients and medical staff who participated in this study.

Compliance with ethical standards

Written informed consent was obtained from the patients separately from the consent provided for the previously reported phase III trial. This study was approved by each participating institute’s institutional review board, and it complied with the provisions of the Declaration of Helsinki and local laws and regulations.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Supplementary material

520_2017_3974_MOESM1_ESM.doc (72 kb)
Table S1 (DOC 72 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2017

Authors and Affiliations

  • Mari Yokoi
    • 1
  • Daiki Tsuji
    • 1
  • Kenichi Suzuki
    • 2
  • Yohei Kawasaki
    • 3
  • Masahiko Nakao
    • 4
  • Hideaki Ayuhara
    • 5
  • Yuuki Kogure
    • 6
  • Kazuhiko Shibata
    • 7
  • Toshinobu Hayashi
    • 8
  • Keita Hirai
    • 1
  • Kazuyuki Inoue
    • 1
  • Toshihiro Hama
    • 2
  • Koji Takeda
    • 9
  • Makoto Nishio
    • 10
  • Kunihiko Itoh
    • 1
  1. 1.Department of Clinical Pharmacology & Genetics, School of Pharmaceutical SciencesUniversity of ShizuokaShizuokaJapan
  2. 2.Department of Pharmacy, Japanese Foundation for Cancer ResearchCancer Institute HospitalTokyoJapan
  3. 3.Department of Drug Evaluation and Informatics, School of Pharmaceutical SciencesUniversity of ShizuokaShizuokaJapan
  4. 4.Department of PharmacyOsaka City General HospitalOsakaJapan
  5. 5.Department of PharmacyTokyo Medical University HospitalTokyoJapan
  6. 6.Department of PharmacyNational Hospital Organization Shikoku Cancer CenterMatsuyamaJapan
  7. 7.Department of Medical OncologyKouseiren Takaoka HospitalTakaokaJapan
  8. 8.Department of PharmacyNational Hospital Organization Kyushu Medical CenterFukuokaJapan
  9. 9.Department of Clinical OncologyOsaka City General HospitalOsakaJapan
  10. 10.Department of Thoracic Medical Oncology, Japanese Foundation for Cancer ResearchCancer Institute HospitalTokyoJapan

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