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Plasma alpha-1-acid glycoprotein as a potential predictive biomarker for non-haematological adverse events of docetaxel in breast cancer patients
Authors:Rafid Salim Jabir  Gwo Fuang Ho  Muhammad Azrif Bin Ahmad Annuar
Affiliation:1. Pharmacotherapeutics Unit, Department of Medicine, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia;2. Clinical Oncology Unit, University Malaya Medical Centre, Kuala Lumpur, Malaysia;3. Radiotherapy &4. Oncology, Universiti Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, Bandar Tun Razak, Kuala Lumpur, Malaysia
Abstract:Context: 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.

Objective: 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).

Materials and methods: 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.

Results: 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.

Conclusions: This study proposes plasma AAG as a potential predictive biomarker of docetaxel non-haematological AEs namely oral mucositis and rash.
Keywords:AAG  docetaxel  oral mucositis  rash  adverse events
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