Pharmacogenetic impact of docetaxel on neoadjuvant treatment of breast cancer patients. (7th September 2018)

• Record Type: Journal Article
• Authors: Sim, Sarah; Bergh, Jonas; Hellström, Mats; Hatschek, Thomas; Xie, Hanjing
• Is Part Of: Pharmacogenomics. Volume 19:Number 16(2018)
• Page Start: 1259
• Page End: 1268
• Publication Date: 2018-09-07
• Subjects: breast cancer -- docetaxel -- personalized medicine -- pharmacogenetics; Pharmacogenomics -- Periodicals; 615.1
• DOI: 10.2217/pgs-2018-0080
• Languages: English
• ISSNs: 1462-2416

Abstract

Aim: This study aimed to investigate the effect of CYP3A4 and CYP3A5 genotypes on clinical outcomes of docetaxel treatment.Patients & methods: In the PROMIX trial, 150 breast cancer patients received docetaxel preoperatively. CYP3A4 and CYP3A5 genotype combinations were transformed into total CYP 3A phenotypes.Results: Seven patients were characterized as poor metabolizer (PM), 22 patients as extensive metabolizer and 121 patients as intermediate metabolizer. The frequency of grade 3/grade 4 adverse events was higher in the PM group (p = 0.002). One PM subject who basically lacked enzyme activity died from typhlitis. Total 45 recurrences were reported after a median of 5-year follow-up; none of these was PM.Conclusion: The allelic variants CYP3A4*22 and CYP3A5*3 contribute to the interpatient variations of docetaxel.