Journal
CANCER GENOMICS & PROTEOMICS
Volume 20, Issue 1, Pages 9-17Publisher
INT INST ANTICANCER RESEARCH
DOI: 10.21873/cgp.20360
Keywords
Multiple myeloma; melphalan; pharmacokinetics
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This study aimed to evaluate the potential impacts of CYP3A4*1B and CYP3A5*3 gene variations on the pharmacokinetic properties of melphalan and clinical outcomes in multiple myeloma patients. The results showed that CYP3A4*1B/*1B and CYP3A5*3/*3 carriers had shorter median progression-free survival time and higher maximum melphalan plasma concentration. Through yet-to-be-identified mechanisms, CYP3A4*1B/*1B and CYP3A5*3/*3 variations might influence melphalan therapy in MM patients.
Background/Aim: There exists considerably large interpatient variability in pharmacokinetic exposure of high dose melphalan in multiple myeloma patients with hematopoietic stem-cell transplantation. In this study, we aimed to evaluate the potential impacts of CYP3A4*1B (rs2940574) and CYP3A5*3 (rs776746) variations on pharmacokinetic properties of melphalan and clinical outcomes in multiple myeloma (MM) patients. Patients and Methods: Genotypes of CYP3A4*1B (rs2940574) and CYP3A5*3 (rs776746) were determined by validated gene -specific real-time PCR (RT-PCR) assays using DNA samples from 108 MM patients; plasma concentrations of melphalan at different time points were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Results: CYP3A4*1B/*1B and CYP3A5*3/*3 carriers appeared to have a short median progression-free survival time and a higher maximum melphalan plasma concentration than non-carriers [792 vs. over 950 days, p=0.08; 9.91 (2.67, 34.03) vs. 8.66 (4.46, 17.61) mg/l, p=0.039]. Conclusion: CYP3A4*1B/*1B and CYP3A5*3/*3 variations might influence melphalan therapy in MM patients through yet-to-be-identified mechanisms.
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