Authors (including presenting author) :
Chan, DCW(1), Wong FCK (2), Fong, KHA(1), Shum, CY(1)
Affiliation :
(1) Department of Oncology, Princess Margaret Hospital, (2) Department of Pathology, Division of Chemical Pathology, Queen Mary Hospital
Introduction :
Pre-emptive testing for dihydropyrimidine dehydrogenase (DPD) deficiency is currently recommended for the prevention of fluoropyrimidine chemotherapy toxicity with multiple guidelines published in different parts of the world. Since only 25% of patients with a decreased DPD enzyme activity carries one of the four common DPD variants, and these variants rarely occur in the Chinese population, genotyping is less preferred as the method of testing amongst the Chinese population. Phenotype testing using serum uracil was shown to correlate better with DPD activity in peripheral blood mononuclear cells (PBMCs) than dihydrouracil (UH2)/ uracil (U) ratio and is superior to UH2/U ratio as a predictor of severe toxicity. DPD deficiency phenotype testing using serum uracil measurement is recommended by the European Medicines Agency and has been adopted in France since 2018 using a cutoff of >=16 ng/mL. The Hospital Authority has started DPD deficiency phenotype testing using serum uracil since May, 2024 for all cancer patients planned to receive fluoropyrimidine-based chemotherapy regimens for their systemic anti-cancer treatment.
Objectives :
The primary objective of this study is to evaluate the incidence of DPD deficiency detected by phenotype testing using serum uracil amongst cancer patients planned to receive fluoropyrimidine-based chemotherapy regimens in the Kowloon West Cluster and to review the toxicity experienced by them.
Methodology :
In this observational study, the incidence of DPD deficiency identified using serum uracil testing was evaluated and its clinical impact on cancer patients receiving fluoropyrimidine-based chemotherapy regimens were reviewed and toxicity recorded according to the Common Terminology Criteria for Adverse Events (CTCAE) criteria from May 8, 2024 to December 31, 2024.
Result & Outcome :
Between May 8, 2024 to December 31, 2024, 521 cancer patients who were planned to receive a fluoropyrimidine-based chemotherapy regimen was tested for their serum uracil level. A total of 40/521 (7.7%) patients were found to have an elevated serum uracil level of >=16 ng/mL. The range of the serum uracil level of these 40 patients were 16-42 ng/mL. All 40 patients were considered to be partially deficient for DPD. No complete DPD deficient patient was identified. Of the 40 patients who were partially deficient for DPD, 25/40 (62.5%) went on to receive a fluoropyrimidine-based chemotherapy regimen. The toxicity experienced by 22 of the patients, whose serum uracil levels were in the range of 16-20 ng/mL, after receiving fluoropyrimidine-based chemotherapy were as follows: none of the patients experienced significant toxicity in terms of neutropenia, thrombocytopenia, or conjunctivitis; Patients who did develop toxicity included 3/22 (14%) with mucositis; 3/22 (14%) with nausea and vomiting; 8/22 (36%) with diarrhea; 2/22 (9%) with hand-foot syndrome; and 3/22 (14%) with increased creatinine, all of which were grade 2 or below. There were two patients who experienced grade 3 toxicities, 1/22 (4.5%) developed anemia due to tumour bleeding; 2/22 (9%) developed liver enzyme dysfunction, of which 1/22 (4.5%) was grade 3 but related to pre-existing fatty liver disease.
Conclusion:
Pre-emptive DPD phenotype testing by serum uracil identified 7.7% of patients to be partially deficient for DPD. Significant toxicity was uncommon amongst patients with partial DPD deficiency with a serum uracil range of 16-20 ng/mL and administration of fluoropyrimidine-based regimens were generally safe. Dose reduction is at the discretion of the treating physician and may not be necessary, especially for patients who have a serum uracil level ranging between 16-20 ng/mL, unless those patients have other concomitant risks of developing significant toxicity such as impaired renal function, pre-existing liver disease, poor performance status.
