Introduction: In this study (PRECISE), we assess the clinical utility of a germline DNA sequencing-based test (ToxNav) for mutations in DPYD and ENOSF1 genes to alter clinician-prescribed fluoropyrimidine doses and the use of a digital application (PROMinet) to record patient-reported chemotherapy toxicity.
Materials and methods: Adult patients with a histological diagnosis of colorectal cancer (CRC) who consented to fluoropyrimidine-based chemotherapy were recruited prospectively and given a digital application to monitor and record associated toxicities. Patient samples were analyzed for 18 germline coding variants in DPYD and 1 ENOSF1 variant.
Results: Genetic testing was performed for 60 patients and identified one patient at increased risk of fluoropyrimidine-based toxicities. Uptake of genetic testing was high and results were available on average 17 days from initial clinical encounter. Patient-reported chemotherapy toxicity identified differences in 5-fluorouracil vs capecitabine regime profiles and identified profiles associated with subsequent need for chemotherapy dose reduction and hospital admission.
Discussion: The PRECISE clinical trial demonstrated that a germline DNA sequencing-based test can provide clinically relevant information to alter clinicians' fluoropyrimidine prescription. The study also obtained high volume, high granularity patient-reported toxicity data that might allow the improvement and personalization of chemotherapy management.
Keywords: Colorectal cancer; DPYD; ENOSF1; chemotherapy; fluoropyrimidine; genetic testing; germline; toxicity; toxicity monitoring.
© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.