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

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

Acknowledgements

The authors would like to thank the Ministry of Higher Education (MOHE), Malaysia and University Malaya for funding this project through the Fundamental Research Grant Scheme (04-04-10-848FR) and High Impact Research (UM.C/625/1/HIR) grants, respectively. Utmost appreciation is extended to the patients who participated in the study.

Disclosure statement

None of the authors declare any competing interests in the matters related to this paper.

Additional information

Funding

The authors would like to thank the Ministry of Higher Education (MOHE), Malaysia and University Malaya for funding this project through the Fundamental Research Grant Scheme (04-04-10-848FR) and High Impact Research (UM.C/625/1/HIR) grants, respectively.