Mari Yokoi1, Daiki Tsuji2, Kenichi Suzuki3, Yohei Kawasaki4, Masahiko Nakao5, Hideaki Ayuhara6, Yuuki Kogure7, Kazuhiko Shibata8, Toshinobu Hayashi9, Keita Hirai1, Kazuyuki Inoue1, Toshihiro Hama3, Koji Takeda10, Makoto Nishio11, Kunihiko Itoh1. 1. Department of Clinical Pharmacology & Genetics, School of Pharmaceutical Sciences, University of Shizuoka, 52-1, Yada, Suruga-ku, Shizuoka, Shizuoka, 422-8002, Japan. 2. Department of Clinical Pharmacology & Genetics, School of Pharmaceutical Sciences, University of Shizuoka, 52-1, Yada, Suruga-ku, Shizuoka, Shizuoka, 422-8002, Japan. d-tsuji@u-shizuoka-ken.ac.jp. 3. Department of Pharmacy, Japanese Foundation for Cancer Research, Cancer Institute Hospital, Tokyo, Japan. 4. Department of Drug Evaluation and Informatics, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan. 5. Department of Pharmacy, Osaka City General Hospital, Osaka, Japan. 6. Department of Pharmacy, Tokyo Medical University Hospital, Tokyo, Japan. 7. Department of Pharmacy, National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan. 8. Department of Medical Oncology, Kouseiren Takaoka Hospital, Takaoka, Japan. 9. Department of Pharmacy, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan. 10. Department of Clinical Oncology, Osaka City General Hospital, Osaka, Japan. 11. Department of Thoracic Medical Oncology, Japanese Foundation for Cancer Research, Cancer Institute Hospital, Tokyo, Japan.
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 receivingcisplatin-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.
RCT Entities:
PURPOSE: Younger age and female sex have already been well-known risk factors for chemotherapy-induced nausea and vomiting (CINV), and 30-50% of cancerpatients 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.
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