Daiki Tsuji1, Megumi Matsumoto2, Yohei Kawasaki3, Yong-I L Kim4,5, Keisuke Yamamoto6, Hidenori Nakamichi6, Yuri Sahara2, Ryo Makuta2, Mari Yokoi2, Takehiro Miyagi2, Kunihiko Itoh2. 1. Department of Clinical Pharmacology and Genetics, School of Pharmaceutical Sciences, University of Shizuoka, 52-1, Yada, Suruga-ku, Shizuoka-shi, Shizuoka, 422-8002, Japan. d-tsuji@u-shizuoka-ken.ac.jp. 2. Department of Clinical Pharmacology and Genetics, School of Pharmaceutical Sciences, University of Shizuoka, 52-1, Yada, Suruga-ku, Shizuoka-shi, Shizuoka, 422-8002, Japan. 3. Biostatistics Section, Clinical Research Center, Chiba University Hospital, Chiba, Japan. 4. Department of Medical Oncology, Seirei Hamamatsu General Hospital, Hamamatsu, Japan. 5. Department of Medical Oncology, Yodogawa Christian Hospital, Osaka, Japan. 6. Department of Pharmacy, Seirei Hamamatsu General Hospital, Hamamatsu, Japan.
Abstract
PURPOSE: Chemotherapy-induced nausea and vomiting (CINV) can lead to a significant deterioration in the quality of life of cancer patients receiving chemotherapy. This study aimed to determine whether ABCB1 2677G > T/A was associated with complete response (CR; defined as no vomiting and no rescue medication) in acute phase (CR0-24), as well as to explore the genetic factors affecting delayed phase (CR24-120) CINV in cancer patients treated with a standard triple antiemetic regimen that included aprepitant. METHODS: This prospective single-center study included a total of 166 chemotherapy-naïve patients with breast cancer who received a standard dose of doxorubicin and cyclophosphamide combination chemotherapy; granisetron, dexamethasone, and aprepitant were administered prior to chemotherapy. CR0-24 was compared between minor allele homozygous (TT, AA, and TA) and major allele homozygous plus heterozygous (GG, GA, and GT) groups of ABCB1 2677G > T/A. In addition, 14 genetic polymorphisms were genotyped and their associations with CRs were investigated. RESULTS: The proportion of patients who achieved CR0-24, which was the primary endpoint of this study, was 59% in the minor allele homozygous and 61% in the major allele homozygous plus heterozygous groups of ABCB1 2677G > T/A. Although this difference was not statistically significant, multivariate logistic regression analysis adjusted for potential risk factors showed that TACR1 1323TT (OR, 2.57; P = 0.014) was a significant determinant of CR24-120. CONCLUSION: No significant association was found between ABCB1 2677G > T/A and CR0-24. However, it was observed that the polymorphism of TACR1, which encodes the neurokinin 1 receptor, might be a potential genetic risk factor for the development of delayed phase CINV.
PURPOSE: Chemotherapy-induced nausea and vomiting (CINV) can lead to a significant deterioration in the quality of life of cancerpatients receiving chemotherapy. This study aimed to determine whether ABCB1 2677G > T/A was associated with complete response (CR; defined as no vomiting and no rescue medication) in acute phase (CR0-24), as well as to explore the genetic factors affecting delayed phase (CR24-120) CINV in cancerpatients treated with a standard triple antiemetic regimen that included aprepitant. METHODS: This prospective single-center study included a total of 166 chemotherapy-naïve patients with breast cancer who received a standard dose of doxorubicin and cyclophosphamide combination chemotherapy; granisetron, dexamethasone, and aprepitant were administered prior to chemotherapy. CR0-24 was compared between minor allele homozygous (TT, AA, and TA) and major allele homozygous plus heterozygous (GG, GA, and GT) groups of ABCB1 2677G > T/A. In addition, 14 genetic polymorphisms were genotyped and their associations with CRs were investigated. RESULTS: The proportion of patients who achieved CR0-24, which was the primary endpoint of this study, was 59% in the minor allele homozygous and 61% in the major allele homozygous plus heterozygous groups of ABCB1 2677G > T/A. Although this difference was not statistically significant, multivariate logistic regression analysis adjusted for potential risk factors showed that TACR1 1323TT (OR, 2.57; P = 0.014) was a significant determinant of CR24-120. CONCLUSION: No significant association was found between ABCB1 2677G > T/A and CR0-24. However, it was observed that the polymorphism of TACR1, which encodes the neurokinin 1 receptor, might be a potential genetic risk factor for the development of delayed phase CINV.
Entities:
Keywords:
ABCB1 polymorphism; Aprepitant; Breast cancer; Chemotherapy-induced nausea and vomiting (CINV); TACR1 polymorphism
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