ABCBl、5-HT3B 受体和 CYP2D6 基因多态性与昂丹司琼和甲氧氯普胺止吐反应在接受高致吐性化疗的印度尼西亚癌症患者中的相关性。

Association of ABCB1, 5-HT3B receptor and CYP2D6 genetic polymorphisms with ondansetron and metoclopramide antiemetic response in Indonesian cancer patients treated with highly emetogenic chemotherapy.

机构信息

Department of Pharmacy, Ahmad Dahlan University, Yogyakarta, Indonesia.

出版信息

Jpn J Clin Oncol. 2011 Oct;41(10):1168-76. doi: 10.1093/jjco/hyr117. Epub 2011 Aug 11.

DOI:10.1093/jjco/hyr117

PMID:21840870

Abstract

OBJECTIVE

Suboptimal treatment of chemotherapy-induced nausea and vomiting and unsatisfactory response to antiemetic drugs cause impairment of cancer patient's daily functioning. This study was aimed to investigate the association of selected germline polymorphisms with ondansetron and metoclopramide response in Indonesian cancer patients treated with highly emetogenic chemotherapy.

METHODS

We enrolled 202 chemotherapy naïve patients treated with cisplatin at a dosage of ≥50 mg/m(2) as monotherapy or as combined chemotherapy. Ondansetron 8 mg and dexamethasone 8 mg intravenously were the standard antiemetic therapy for prevention of acute chemotherapy-induced nausea and vomiting. Metoclopramide 10 mg orally, three times per day as fixed prescription, was given until 5 days after chemotherapy to prevent delayed chemotherapy-induced nausea and vomiting. Primary and secondary outcomes were the occurrence of chemotherapy-induced nausea and vomiting in the acute and delayed phase. The following single-nucleotide polymorphisms were determined in ABCB1: rs1045642, rs2032582 and rs1128503; in 5-HT3B-R: rs45460698, rs4938058 and rs7943062; and in CYP2D6: rs16947 (CYP2D6 2), rs3892097 (CYP2D6 4) and rs1065852 (CYP2D6 10) using Taqman assays.

RESULTS

During the acute phase, 21.8 and 30.2% patients experienced Grade 3 and 4 nausea and vomiting, respectively, whereas 38.6% patients experienced nausea and/or vomiting in the delayed phase. Carriers of the CTG haplotype of the ABCB1 gene experienced Grade 3 and 4 chemotherapy-induced nausea and vomiting more often than other haplotypes in the delayed phase (P< 0.05). No associations were found with the 5-HT3B receptor haplotypes and CYP2D6-predicted phenotypes.

CONCLUSIONS

Our study shows that in Indonesian cancer patients treated with highly cytostatic emetogenic, carriership of the CTG haplotype of the ABCB1 gene is related to an increased risk of delayed chemotherapy-induced nausea and vomiting.

摘要

目的

化疗引起的恶心和呕吐的治疗不充分以及止吐药物的反应不佳导致癌症患者的日常功能受损。本研究旨在调查选定的种系多态性与昂丹司琼和甲氧氯普胺在接受高致吐性化疗的印度尼西亚癌症患者中的反应之间的关联。

方法

我们招募了 202 名接受顺铂治疗的化疗初治患者，顺铂剂量≥50mg/m2，单药或联合化疗。昂丹司琼 8mg 和地塞米松 8mg 静脉内给药是预防急性化疗引起的恶心和呕吐的标准止吐治疗。甲氧氯普胺 10mg，每日口服 3 次，作为固定处方，用于预防迟发性化疗引起的恶心和呕吐，直至化疗后 5 天。主要和次要结局是急性和迟发性化疗引起的恶心和呕吐的发生。在 ABCB1 中确定了以下单核苷酸多态性：rs1045642、rs2032582 和 rs1128503；在 5-HT3B-R 中：rs45460698、rs4938058 和 rs7943062；在 CYP2D6 中：rs16947（CYP2D6 2）、rs3892097（CYP2D6 4）和 rs1065852（CYP2D6 10）使用 Taqman 测定法。

结果

在急性阶段，分别有 21.8%和 30.2%的患者出现 3 级和 4 级恶心和呕吐，而 38.6%的患者在迟发性阶段出现恶心和/或呕吐。ABCB1 基因的 CTG 单倍型携带者在迟发性阶段比其他单倍型更易发生 3 级和 4 级化疗引起的恶心和呕吐（P<0.05）。与 5-HT3B 受体单倍型和 CYP2D6 预测表型无关联。