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Impact of CYP2D6 Polymorphisms on Tamoxifen Treatment in Patients With Retroperitoneal Fibrosis: A First Step Towards
Nici Markus Dreger1, Stephan Degener1, Stephan Roth1
1Department of Urology, Helios University Hospital Wuppertal, University of Witten/Herdecke, Wuppertal, Germany.
Objective:
To investigate the influence of CYP2D6 polymorphisms on outcomes and health-related quality of life of patients with retroperitoneal fibrosis (RPF) receiving tamoxifen (TMX). TMX is an effective alternative to corticosteroids for patients with RPF. Conversion of TMX to more potent endoxifen is dependent on enzyme activity of CYP2D6.
Materials And Methods:
CYP2D6 genotyping and phenotype prediction of all patients treated with TMX between 02/2007 and 01/2018 was assessed using multiplex polymerase chain reaction (PCR). Groups were classified by phenotype: extensive (EM) vs poor and intermediate (PM + IM) vs ultrarapid metabolizer (UM). Retrospective evaluation of outcome (including magnetic resonance imaging and positron emission tomography-computed tomography) and health-related quality of life using the SF-36 was performed.
Results:
A total of 63/194 patients received TMX, 40/63 with complete follow-up were sequenced: Twenty-nine patients with EM phenotype, 8 PM + IM and 3 UM. The median therapy duration was 364.5 days with a mean follow-up of 62.9 months. Seven therapy terminations occurred due to lack of response (17.5%), including all UM patients (P <.001). Magnetic resonance imagings showed a regression of fibrosis for EM and PM + IM in 69% and 62.5% of cases and a progression for UM in 100% (P = .004). In positron emission tomography-computed tomography, glucose utilization of RPF decreased significantly for EM and PM + IM. The physical sum-score of SF-36 improved for EM and PM + IM and decreased for UM (P <.05). The removal of DJ-stents was successful for EM, PM + IM, and UM in 48.3%, 75%, and 0% of cases (P = .0581).
Conclusion:
Contrary to expectations, UM showed the lowest success rate, which concludes that genotyping of RPF-patients may be useful in the sense of a tailored-therapy.
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