Jabir Rafid Salim, Ho Gwo Fuang, Annuar Muhammad Azrif Bin Ahmad, Stanslas Johnson
a Pharmacotherapeutics Unit, Department of Medicine, Faculty of Medicine and Health Sciences , Universiti Putra Malaysia , Serdang , Selangor , Malaysia.
b Clinical Oncology Unit , University Malaya Medical Centre , Kuala Lumpur , Malaysia.
Biomarkers. 2018 Mar;23(2):142-146. doi: 10.1080/1354750X.2017.1334152. Epub 2017 Jun 6.
Rash and oral mucositis are major non-haematological adverse events (AEs) of docetaxel, in addition to fatigue, nausea, vomiting and diarrhoea, which restrict the use of the drug in cancer therapy. Alpha-1-acid glycoprotein (AAG) is an acute phase reactant glycoprotein and is a primary carrier of docetaxel in the blood. Docetaxel has extensive binding (>98%) to plasma proteins such as AAG, lipoproteins and albumin.
To study the association between plasma AAG level and non-haematological AEs of docetaxel in Malaysian breast cancer patients of three major ethnic groups (Malays, Chinese and Indians).
One hundred and twenty Malaysian breast cancer patients receiving docetaxel as single agent chemotherapy were investigated for AAG plasma level using enzyme-linked immunosorbent assay technique. Toxicity assessment was determined using Common Terminology Criteria of Adverse Events v4.0. The association between AAG and toxicity were then established.
There was interethnic variation of plasma AAG level; it was 182 ± 85 mg/dl in Chinese, 237 ± 94 mg/dl in Malays and 240 ± 83 mg/dl in Indians. It was found that low plasma levels of AAG were significantly associated with oral mucositis and rash.
This study proposes plasma AAG as a potential predictive biomarker of docetaxel non-haematological AEs namely oral mucositis and rash.
除疲劳、恶心、呕吐和腹泻外,皮疹和口腔黏膜炎是多西他赛主要的非血液学不良事件(AE),这些限制了该药物在癌症治疗中的应用。α1-酸性糖蛋白(AAG)是一种急性期反应糖蛋白,是血液中多西他赛的主要载体。多西他赛与血浆蛋白如AAG、脂蛋白和白蛋白有广泛的结合(>98%)。
研究马来西亚三个主要种族(马来人、华人、印度人)乳腺癌患者血浆AAG水平与多西他赛非血液学不良事件之间的关联。
采用酶联免疫吸附测定技术,对120例接受多西他赛单药化疗的马来西亚乳腺癌患者的血浆AAG水平进行检测。使用不良事件通用术语标准第4.0版进行毒性评估。然后确定AAG与毒性之间的关联。
血浆AAG水平存在种族差异;华人中为182±85mg/dl,马来人中为237±94mg/dl,印度人中为240±83mg/dl。发现血浆AAG水平低与口腔黏膜炎和皮疹显著相关。
本研究提出血浆AAG作为多西他赛非血液学不良事件(即口腔黏膜炎和皮疹)的潜在预测生物标志物。