ArticleBritish journal of clinical pharmacology2016
Beating the odds: efficacy and toxicity of dihydropyrimidine dehydrogenase-driven adaptive dosing of 5-FU in patients with digestive cancer.
Article in British journal of clinical pharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 52 citations in OpenAlex.
- Food-effect study on uracil and dihydrouracil plasma levels as marker for dihydropyrimidine dehydrogenase activity in human volunteers.British journal of clinical pharmacology · 2018Trial
- Management of patients with reduced dihydropyrimidine dehydrogenase activity receiving combined 5-fluoruracil-/capecitabine-based chemoradiotherapy.Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] · 2025Article
- TRIB3 as a biomarker of gastric cancer cell sensitivity to chemotherapeutic agents running title: A protective role of TRIB3 on chemotherapy.SAGE open medicine · 2024Article
- 5-Fluorouracil Neurotoxicity in a Patient With Normal Dihydropyrimidine Dehydrogenase Activity.Cureus · 2023Article
- Article
- Survey of US Medical Oncologists' Practices and Beliefs RegardingJCO oncology practice · 2022Article
- Endogenous metabolic markers for predicting the activity of dihydropyrimidine dehydrogenase.Clinical and translational science · 2022Article
- Pretherapeutic screening for Dihydropyrimidine deshydrogenase deficiency in measuring uracilemia in dialysis patients leads to a high rate of falsely positive results.Cancer chemotherapy and pharmacology · 2021Article
- Overexpression of sortilin is associated with 5-FU resistance and poor prognosis in colorectal cancer.Journal of cellular and molecular medicine · 2021Article
- Ethnic Diversity of DPD Activity and thePharmacogenomics and personalized medicine · 2021Review
- A Simple and Rapid UPLC-UV Method for Detecting DPD Deficiency in Patients With Cancer.Clinical and translational science · 2020Article
- In-Vivo Retention of 5-Fluorouracil UsingScientific reports · 2019Article
- Tailored therapy in patients treated with fluoropyrimidines: focus on the role of dihydropyrimidine dehydrogenase.Cancer drug resistance (Alhambra, Calif.) · 2019Review
- The use of pharmacogenetics to increase the safety of colorectal cancer patients treated with fluoropyrimidines.Cancer drug resistance (Alhambra, Calif.) · 2019Review
- 5-FU therapeutic drug monitoring as a valuable option to reduce toxicity in patients with gastrointestinal cancer.Oncotarget · 2018Article
- Article
- UPFRONT DPD DEFICIENCY DETECTION TO SECURE 5-FU ADMINISTRATION: PART 2- APPLICATION TO HEAD-AND-NECK CANCER PATIENTS.Clinical cancer drugs · 2017Article
- Antiproliferative activities of Amaryllidaceae alkaloids from Lycoris radiata targeting DNA topoisomerase I.Scientific reports · 2016Article
- Pronounced between-subject and circadian variability in thymidylate synthase and dihydropyrimidine dehydrogenase enzyme activity in human volunteers.British journal of clinical pharmacology · 2016Article
- Beating the odds: efficacy and toxicity of dihydropyrimidine dehydrogenase-driven adaptive dosing of 5-FU in patients with digestive cancer.British journal of clinical pharmacology · 2016Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims5-FU is the backbone of most regimens in digestive oncology. Administration of standard 5-FU leads to 15-30% of severe side effects, and lethal toxicities are regularly reported with fluoropyrimidine drugs. Dihydropyrimidine dehydrogenase (DPD) deficiency is a pharmacogenetic syndrome responsible for most cases of life-threatening toxicities upon 5-FU intake, and pre-treatment checking for DPD status should help to reduce both incidence and severity of side effects through adaptive dosing strategies.
methodsWe have used a simple method for rapidly establishing the DPD phenotype of patients with cancer and used it prospectively in 59 routine patients treated with 5-FU-based therapy for digestive cancers. No patient with total DPD deficiency was found but 23% of patients exhibited poor metabolizer phenotype, and one patient was phenotyped as profoundly deficient. Consequently, 5-FU doses in poor metabolizer patients were cut by an average 35% as compared with non deficient patients (2390 ± 1225 mg vs. 3653 ± 1371 mg, P < 0.003, t-test).
resultsDespite this marked reduction in 5-FU dosing, similar efficacy was achieved in the two subsets (clinical benefit: 40 vs. 43%, stable disease: 40 vs. 37%, progressive disease: 20% in both subsets, P = 0.893, Pearson's chi-square). No difference in toxicities was observed (P = 0.104, Fisher's exact test). Overall, only 3% of early severe toxicities were recorded, a value markedly lower than the 15-30% ones usually reported with 5-FU.
conclusionsThis feasibility study shows how simplified DPD-based adaptive dosing of 5-FU can reduce sharply the incidence of treatment-related severe toxicities while maintaining efficacy as part of routine clinical practice in digestive oncology.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.