Trial reportBritish journal of cancer2017
Dihydropyrimidine dehydrogenase pharmacogenetics for predicting fluoropyrimidine-related toxicity in the randomised, phase III adjuvant TOSCA trial in high-risk colon cancer patients.
Trial report in British journal of cancer, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
45 citing papers in PubMed, 2 syntheses or guidelines pooled it, 68 citations in OpenAlex.
- Pooled it
- A systematic review and meta-analysis of the impacts of germline pharmacogenomics on severe toxicity and symptom burden in adult patients with cancer.Clinical and translational science · 2024Pooled it
- Sex-Related Differences in Impact on Safety of Pharmacogenetic Profile for Colon Cancer Patients Treated with FOLFOX-4 or XELOX Adjuvant Chemotherapy.Scientific reports · 2019Trial
- Allelic Variants of theGenes · 2026Observational
- Uptake of DPYD and UGT1A1 testing in Italy and adherence to pharmacogenetic guidelines: A 5-year perspective from an EQA provider.British journal of clinical pharmacology · 2026Article
- Gene, genetics and genetic medicines in gastroenterology: Current status and its future.World journal of gastroenterology · 2026Review
- Navigating Cardiotoxicity in Cancer Treatment: Insights into Fluoropyrimidine-induced Cardiac Events.Current cardiology reviews · 2026Review
- Dihydropyrimidine dehydrogenase polymorphisms in patients with gastrointestinal malignancies and their impact on fluoropyrimidine tolerability: Experience from a single Italian institution.World journal of gastrointestinal oncology · 2025Article
- Article
- Article
- Pharmacogenetics of colorectal cancer in a third-level hospital in Valencia.Advances in laboratory medicine · 2024Article
- Lethal 5-Fluorouracil Toxicity in a Carrier ofJCO precision oncology · 2024Article
- Article
- Complete DPYD genotyping combined with dihydropyrimidine dehydrogenase phenotyping to prevent fluoropyrimidine toxicity: A retrospective study.Cancer medicine · 2024Article
- Discussion on the optimization of personalized medication using information systems based on pharmacogenomics: an example using colorectal cancer.Frontiers in pharmacology · 2024Review
- Precision fluoropyrimidines dosing in a compound heterozygous variant carrier of the DPYD gene: a case report.Cancer chemotherapy and pharmacology · 2023Article
- Review
- Implementing pharmacogenetic testing in fluoropyrimidine-treated cancer patients:Frontiers in pharmacology · 2023Article
- Pharmacogenetic Practice of Anticancer Drugs: Multiple Approaches for an Accurate and Comprehensive Genotyping.Pharmacogenomics and personalized medicine · 2023Article
- Ten-year experience with pharmacogenetic testing forFrontiers in pharmacology · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
30 authors at 20 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDihydropyrimidine dehydrogenase (DPD) catabolises ∼85% of the administered dose of fluoropyrimidines. Functional DPYD gene variants cause reduced/abrogated DPD activity. DPYD variants analysis may help for defining individual patients' risk of fluoropyrimidine-related severe toxicity.
methodsThe TOSCA Italian randomised trial enrolled colon cancer patients for 3 or 6 months of either FOLFOX-4 or XELOX adjuvant chemotherapy. In an ancillary pharmacogenetic study, 10 DPYD variants (*2A rs3918290 G>A, *13 rs55886062 T>G, rs67376798 A>T, *4 rs1801158 G>A, *5 rs1801159 A>G, *6 rs1801160 G>A, *9A rs1801265 T>C, rs2297595 A>G, rs17376848 T>C, and rs75017182 C>G), were retrospectively tested for associations with ⩾grade 3 fluoropyrimidine-related adverse events (FAEs). An association analysis and a time-to-toxicity (TTT) analysis were planned. To adjust for multiple testing, the Benjamini and Hochberg's False Discovery Rate (FDR) procedure was used.
resultsFAEs occurred in 194 out of 508 assessable patients (38.2%). In the association analysis, FAEs occurred more frequently in *6 rs1801160 A allele carriers (FDR=0.0083). At multivariate TTT analysis, significant associations were found for *6 rs1801160 A allele carriers (FDR<0.0001), *2A rs3918290 A allele carriers (FDR<0.0001), and rs2297595 GG genotype carriers (FDR=0.0014). Neutropenia was the most common FAEs (28.5%). *6 rs1801160 (FDR<0.0001), and *2A rs3918290 (FDR=0.0004) variant alleles were significantly associated with time to neutropenia.
conclusionsThis study adds evidence on the role of DPYD pharmacogenetics for safety of patients undergoing fluoropyrimidine-based chemotherapy.
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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.