Veiligheid van 5-FU crème (Efudix) in patiënten die drager zijn van een DPYD variant – de DPYDIX studie

Rationale: Recently it was shown that DPYD genotype-based dose reductions improved patient safety of fluoropyrimidine treatment. A limitation of previous research is that the additional value of DPYD genotype-based dosing is based on therapy with 5-fluoropyrimidine (5-FU; intravenous) and capecitabine (oral), while there is a third application of 5-FU; topical 5-FU (Efudix 5% cream). Objective: To study if patients who carry clinically relevant DPYD variants (DPYD*2A, c.2846A>T, c.1236G>A/HapB3, c.1679T>G) are at a higher risk for developing severe 5-FU cream-related toxicity. Study design: Prospective, observational clinical trial. Of patients receiving 5-FU cream, one blood sample will be withdrawn before or during therapy for DPYD genotyping. On five time points (1, 2 and 3 weeks after start therapy, with stop therapy and 3 months after start) adverse events will be evaluated using visual inspection of the treated area and patients will be asked to complete diaries to obtain information about adverse events. Study population: Adult patients planned to receive 5-FU cream are asked to participate in the study. Main study parameters/endpoints: Severe toxicity in patients treated with 5-FU cream. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: The risk of blood withdrawals is negligible.

To prospectively study if patients carrying clinically relevant DPYD variants (DPYD*2A, c.2846A>T, c.1236G>A/HapB3, c.1679T>G) are more at risk for developing moderate/severe vesicles or bullae with 5-FU cream.

First patient inclusion planned in November 2019.

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