Open Access iconOpen Access

ARTICLE

crossmark

Tolerance and Efficacy of Regorafenib according to UGT Pharmacogenetical Status in the Treatment of Metastatic Refractory Colorectal Cancer

Pierre-Guillaume Poureau1,2,*, Estelle Dhamelincourt2, Jessica Nguyen2, Hélène Babey2, Emmanuelle Renaud2, Margaux Geier2, Michèle Boisdron-Celle3, Jean-Philippe Metges2

1 HIA Brest, Rue Colonel Fonferrier, Gastroentérologie, Brest, 29200, France
2 CHU Morvan, 2 Av Foch, Oncologie Digestive, Brest, 29200, France
3 ICO Paul Papin, Pharmacologie Toxicologie Pharmacogénétique, 15 Rue André Bocquel, Angers, 49055, France

* Corresponding Author: Pierre-Guillaume Poureau. Email: email

Oncologie 2021, 23(2), 195-202. https://doi.org/10.32604/Oncologie.2021.015929

Abstract

Introduction: Regorafenib is a multi tyrosin-kinase inhibitor prescribed in metastatic refractory colorectal cancer treatment. Its toxicity is significant but inconstant. The metabolism of regorafenib includes oxydation via cytochrome P3A4, then glucuroconjugation. A pharmacogenetical approach of mutational status of Uridine-Diphospho-Glucuronosyltransfersase (UDP-glucuronosyl-transferase, UGT) could be a strategy to optimise the use of regorafenib. Patients and Method: This is a restrospective, unicentric study. All adult patients treated with regorafenib for a metastatic colorectal cancer in our center between 2013 and 2017 were analysed. UGT1A1 polypmorphism was previously researched in the laboratory after written informed consent. Results: Thirty-five patients received regorafenib during the study period. A TA repetition in UGT1A1 gene was present for 16 patients including two Gilbert syndrome. There were no more adverse events on patients with a heterozygous TA repetition or with a Gilbert syndrome compared with patients without UGT polymorphism, whatever the dosage at initiation of regorafenib. Adverse events grade 2 or superior, and grade 3 or superior tended to be more noticeable when the starting dose was 120 or 160 mg per day compared to 80 mg per day, but not statistically significant. No difference was observed on progression-free survival neither depending on UGT status nor depending on initating dose of regorafenib. Conclusion: This is a preliminary study evaluating safety of regorafenib according to UGT1A1 polymorphism. Larger and prospective studies are needed to evaluate dose-escalation strategy in patients with variable activity of glucuroconidation, especially Gilbert syndrome, or with abnormalities in other UGT enzymes such as UGT1A9.

Keywords


Cite This Article

APA Style
Poureau, P., Dhamelincourt, E., Nguyen, J., Babey, H., Renaud, E. et al. (2021). Tolerance and efficacy of regorafenib according to UGT pharmacogenetical status in the treatment of metastatic refractory colorectal cancer. Oncologie, 23(2), 195-202. https://doi.org/10.32604/Oncologie.2021.015929
Vancouver Style
Poureau P, Dhamelincourt E, Nguyen J, Babey H, Renaud E, Geier M, et al. Tolerance and efficacy of regorafenib according to UGT pharmacogenetical status in the treatment of metastatic refractory colorectal cancer. Oncologie . 2021;23(2):195-202 https://doi.org/10.32604/Oncologie.2021.015929
IEEE Style
P. Poureau et al., “Tolerance and Efficacy of Regorafenib according to UGT Pharmacogenetical Status in the Treatment of Metastatic Refractory Colorectal Cancer,” Oncologie , vol. 23, no. 2, pp. 195-202, 2021. https://doi.org/10.32604/Oncologie.2021.015929



cc Copyright © 2021 The Author(s). Published by Tech Science Press.
This work is licensed under a Creative Commons Attribution 4.0 International License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
  • 1754

    View

  • 1217

    Download

  • 0

    Like

Share Link