Validation of a simple genotyping panel assay for pharmacogenomics of taxane-based therapy: preliminary results

Abstract

Objective: Several strategies for preventing toxicity and resistance to taxane-based chemotherapy have been investigated so far. Lately, findings on the genetic variants associated with neutropenia and neuropathy (N&N) toxicity have been reported. Patients and Methods: A panel assay of single nucleotide polymorphisms (SNP) related to paclitaxel and Docetaxel toxicity on four candidate genes ATP-binding cassette subfamily B member 1 (ABCB1), Beta-tubulin 2A (TUBB2A), Cytochrome P450 3A4* 1B (CYP3A4*1B), Excision-Repair Cross-Complementing group 2 (ERCC3) are validated and discussed. We genotyped 37 cancer patients who received paclitaxel or docetaxel-based therapy. Furthermore, an early outline evaluation of the genotyping costs and benefits was assessed. Results: A total of 37 patients were treated with a taxane of which 17 (45.9%) had adverse N&N events. Pharmacogenomics analysis showed no relation between candidate gene polymorphisms and toxicity, except for the ERCC3 AG+GG allele [OR 2.61 (95% CI: 0.91–7.61)] that showed a significantly weak trend of risk of neurotoxicities vs. the AG allele [OR 1.52 (95% CI: 0.51–4.91)] p=0.03. Conclusions: We propose a useful genotyping panel assay to prevent toxicity in patients undergoing taxane-based therapy at an affordable price, with help from the literature and our experimental results and data. Based on the individual pharmacogenomics profile, clinicians will have additional information to personalize the treatment for the patient to minimize toxicity and maximize benefits, and they can also determine the cost-effectiveness for national healthcare sustainability.

Keywords

• genotyping methods
• docetaxel
• paclitaxel
• abcb1
• mdr1
• beta-tubulin 2a (tubb2a)
• cyp3a4*1b
• ercc2