Pharmacogenetic impact of docetaxel on neoadjuvant treatment of breast cancer patients

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.