Dihydropyrimidine dehydrogenase deficiency in patients treated with 5FU or capecitabine based regimens: A single center experience from South India.

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e15517 Background: DPYD deficiency is present in 3-5% of patients. The risk of treatment-related death in DPYD mutation carriers who receive fluoropyrimidine chemotherapy has been estimated at 3-10%. There is growing data in support of widespread screening for DPYD deficiency prior to fluoropyrimidine chemotherapy. The purpose of our study was to identify the prevalence of DPYD deficiency among patients receiving 5-fluorouracil (5FU) or capecitabine based combination chemotherapy, and to analyse the toxicity profile among the DPYD deficient group. Methods: The study involved patients who have received 5FU and capecitabine based chemotherapy for the treatment for gastrointestinal, breast and head and neck cancers between 2019-2020. Four DPYD variants were checked using real-time PCR based Genotyping assay. Three common DPYD variants recommended by the CPIC guidelines (IVS14+1 G>A (*2A), c.1679T>G (*13), c.2846A>T) and a common variant in Asian population (c.496A>G), based on previous studies, was included in our analysis. These variants were assessed prior to the initiation of the chemotherapy and dose was modified based on the activity score and the toxicity profile was assessed. Descriptive statistics was performed using SPSS version 20. Results: 375 patients were included in this analysis. The median age of the cohort was 61years (21-84 years). 51.3% were males and 49.7% females. Among the 375 patients, 47 patients had DPYD mutation (12.5%). The median age of the DPYD mutated patients were 68 years; 29 (61.7%) males and 18 (38.2%) females. 32 (68.8%) had deleterious mutation in DPYD variant c.496A>G (rs2297595) and 15 (31.9%) showed mutation IVS14+1 G>A (rs3918290). 35 out 47 patients had grade II-III toxicity even after dose reduction during the first cycle of chemotherapy. The commonly seen adverse events were hand and foot syndrome in 18 (38.3%), mucositis in 7 (14.9%), diarrrhoea in 15 (31.9%) and neutropenia in 25 (31.9%) patients. Four patients had febrile neutropenia. One patient experience myocardial infarction. There was no mortality. Chi square analysis showed DPYD mutation had significant association with presence of severe adverse reaction (74.5%, p-value. 0.002). Conclusions: Prevalence of DPYD mutation in our patients was 12.5%. They experienced more toxicities while receiving 5-FU/Capecitabine even after dose modification. c.496A>G (rs2297595) was the most common variant seen in our patients. Screening of patients for DPYD mutations prior to administration of 5-FU/capecitabine using pharmacogenetic methods may help identify those patients who are at risk for adverse effects, allowing a more individualized approach to their chemotherapy management. c.496A>G (rs2297595) variant should also be in included routinely in DPYD screening among South Asian population.