Capecitabine is an oral pro-drug of 5FU. Dihydropyrimidine dehydrogenase (DPD), an enzyme encoded by the DPYD gene, is the rate-limiting step in 5FU catabolism. Life threatening gut wall injury occurs in a significant minority of patients and can potentially be predicted in patients with specific DPYD gene polymorphisms which result in decreased enzyme activity. Presently DPYD testing is performed in a limited number of centres in the UK. We conducted a retrospective cohort study to assess the frequency and cost of admissions due to capecitabine gut wall injury.
Using our electronic health records data base patients treated with capecitabine who were admitted for 3 days or more and had a stool sample were identified from 2010 to 2017. Individual records were reviewed to identify patients who had been admitted with severe gut wall toxicity. A Patient Level Costing System (PLiCS) was used to calculate the cost of each admission. Adverse outcomes are defined as significant morbidity (Admission > 14 days) or mortality.
2626 patients were identified over the 7 year period; 131 were admitted with a history of G2 diarrhoea. (4.9%) 40 with grade 4 toxicity (1.5%); 13 post C1, 25 post C2, 2 post C3 of treatment. Median length of stay 16 days (3 - 46 days). Medical management included loperamide (73%), codeine (45%), octreotide (17.5%) and TPN (10%) Low albumin levels (<34g/L) or neutropenia (<1*9/L) on admission was a predictor for increased length of stay and adverse outcomes. 14 patients admitted for >14 days (35%). 11 patients died due to significant toxicity (0.4% of initial patient cohort) The costs of admission in this patient group using PLiCS analysis is approximately £37,000/annum.
Patients presenting with significant toxicity and the potential for DPYD deficiency have significantly prolonged inpatient stays, increased morbidity and mortality. Baseline bloods are a weak predictor of outcome in this patient group. DPYD testing is near cost neutral, the introduction of routine testing for DPD deficiency would allow oncologists to identify a meaningful proportion of patients at risk of significant toxicity ahead of treatment, and the ability to modify treatment plans accordingly and improve safety.
Clinical trial identification
Legal entity responsible for the study
Leeds Cancer Centre.
Has not received any funding.
All authors have declared no conflicts of interest.