Fluoropyrimidine-Induced Severe Toxicities Associated with Rare DPYD Polymorphisms: Case Series from Saudi Arabia and a Review of the Literature

Nedal Bukhari; Abdulraheem Alshangiti; Emad Tashkandi; Mohammed Algarni; Humaid O Al-Shamsi; Hamoud Al-Khallaf

doi:10.3390/clinpract11030062

Fluoropyrimidine-Induced Severe Toxicities Associated with Rare DPYD Polymorphisms: Case Series from Saudi Arabia and a Review of the Literature

Clin Pract. 2021 Jul 27;11(3):467-471. doi: 10.3390/clinpract11030062.

Authors

Nedal Bukhari^{1

2}, Abdulraheem Alshangiti¹, Emad Tashkandi^{3

4}, Mohammed Algarni^{5

6}, Humaid O Al-Shamsi^{7

8

9}, Hamoud Al-Khallaf¹⁰

Affiliations

¹ Department of Medical Oncology, King Fahad Specialist Hospital, Dammam 31444, Saudi Arabia.
² Department of Internal Medicine, Imam Abdulrahman Bin Faisal University, Dammam 34212, Saudi Arabia.
³ Oncology Centre, King Abdullah Medical City, Makkah 24246, Saudi Arabia.
⁴ College of Medicine, Umm Al-Qura University, Makkah 24211, Saudi Arabia.
⁵ Oncology Department, King Abdulaziz Medical City, Riyadh 11426, Saudi Arabia.
⁶ King Saud bin Abdulaziz University for Health Sciences, Riyadh 11481, Saudi Arabia.
⁷ Department of Oncology, Burjeel Cancer Institute, Burjeel Medical City, Abu Dhabi 999041, United Arab Emirates.
⁸ Emirates Oncology Society, Dubai 22107, United Arab Emirates.
⁹ College of Medicine, University of Sharjah, Sharjah 999041, United Arab Emirates.
¹⁰ Department of Pathology and Laboratory Medicine, King Fahad Specialist Hospital, Dammam 31444, Saudi Arabia.

Abstract

Dihydropyrimidine dehydrogenase (DPD) is the major enzyme in the catabolism of 5-Fluorouracil (5-FU) and its prodrug capecitabine. We report cases from our institute with colorectal cancer who experienced severe toxicities to standard dose 5-FU based chemotherapy. DPYD gene sequencing revealed rare different polymorphisms that prompted dose adjustments of administered 5-FU and capecitabine. To our knowledge, this is the first case series looking at DPYD polymorphisms in the Saudi Arabian population.

Keywords: 5-Fluorouuracil; DPYD; chemotherapy; dihydropyrimidine dehydrogenase; polymorphism.