Sarah Sim1, Jonas Bergh2,3, Mats Hellström2, Thomas Hatschek2,3, Hanjing Xie2,3,4. 1. Department of Physiology & Pharmacology, Karolinska Institutet. SE171-76 Stockholm, Sweden. 2. Department of Clinical Oncology, Karolinska University Hospital, SE171-76 Stockholm, Sweden. 3. Department of Oncology & Pathology, Karolinska institutet, SE171-76 Stockholm, Sweden. 4. Department of Oncology, Capio St Görans Hospital, SE171-76 Stockholm, Sweden.
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.
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 cancerpatients 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.
Entities:
Keywords:
breast cancer; docetaxel; personalized medicine; pharmacogenetics
Authors: Nicholas R Powell; Tyler Shugg; Reynold C Ly; Costantine Albany; Milan Radovich; Bryan P Schneider; Todd C Skaar Journal: Front Oncol Date: 2022-01-31 Impact factor: 6.244
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