Plasma alpha-1-acid glycoprotein as a potential predictive biomarker for non-haematological adverse events of docetaxel in breast cancer patients

Rafid Salim Jabir, Gwo Fuang Ho, Muhammad Azrif Bin Ahmad Annuar, Johnson Stanslas

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 made. There was inter-ethnic 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.