An evaluation of the clinical utility of a panel of variants in DPYD and ENOSF1 for predicting common capecitabine related toxicities

Palles, Claire; Fotheringham, Susan; Chegwidden, Laura; Lucas, Marie Madeleine; Mozolowski, Guy; Tomlinson, Ian; Kerr, David

doi:10.1093/annonc/mdy151.212

Cited by 2 publications

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“…Applications such as pharmacogenetics have also shown promise, particularly in targeting therapies, not only in terms of predicted efficacy, but also for the purpose of avoiding serious AE. With respect to CRC, one of the most prescient applications is the genotyping of patients ahead of receiving fluoropyrimidine-based chemotherapy in order to identify those at risk of severe toxic AE [39]. Liquid biopsy refers to the collection and analysis of circulating tumour cells, cell-free nucleic acid and tumour-derived exosomal vesicles that have been shed by the tumour or metastatic site into a patient’s blood or other fluids.…”

Section: Future Tools For the Stratification Of Early-stage Colon Canmentioning

confidence: 99%

Challenges and solutions in patient treatment strategies for stage II colon cancer

Fotheringham¹,

Mozolowski²,

Murray

et al. 2019

Gastroenterology Report

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Colorectal cancer remains one of the most common cancers worldwide and, despite improvements in treatment options for late-stage metastatic cancer, there are still questions surrounding how best to treat early-stage disease patients. Some recent advances have been made in the staging of cancer and improving the risk assessment of strategies for patient treatment. A number of high-risk features have been proposed that may help to stratify stage II cancer patients into groups that will truly benefit from adjuvant chemotherapy. Diagnostic tests are becoming available to measure these biomarkers, utilizing both currently available and novel technologies. This review will describe the challenges in treatment decisions for early-stage colon cancer and how personalized medicine can assist clinicians in making the best treatment choices for patients with stage II colon cancer in particular.

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Section: Future Tools For the Stratification Of Early-stage Colon Canmentioning

confidence: 99%

Challenges and solutions in patient treatment strategies for stage II colon cancer

Fotheringham¹,

Mozolowski²,

Murray

et al. 2019

Gastroenterology Report

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ToxNav germline genetic testing and PROMinet digital mobile application toxicity monitoring: Results of a prospective single‐center clinical utility study—PRECISE study

Starkey

Sivakumar

et al. 2019

Cancer Medicine

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IntroductionIn 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 methodsAdult 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.ResultsGenetic 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.DiscussionThe 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.

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An evaluation of the clinical utility of a panel of variants in DPYD and ENOSF1 for predicting common capecitabine related toxicities

Cited by 2 publications

References 0 publications

Challenges and solutions in patient treatment strategies for stage II colon cancer

Challenges and solutions in patient treatment strategies for stage II colon cancer

ToxNav germline genetic testing and PROMinet digital mobile application toxicity monitoring: Results of a prospective single‐center clinical utility study—PRECISE study

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