Genetic risk factors for chemotherapy-induced nausea and vomiting in patients with cancer receiving cisplatin-based chemotherapy
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.
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.
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.
ERCC1 polymorphism influenced the extent of CINV control in patients receiving cisplatin-based chemotherapy.
Clinical trial information: UMIN 000009335
KeywordsChemotherapy-induced nausea and vomiting (CINV) ERCC1 polymorphism Cisplatin Granisetron Palonosetron Aprepitant
We wish to thank all the patients and medical staff who participated in this study.
This work was supported by JSPS KAKENHI Grant Number 26860110.
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.
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