Evidence map›Paper›PMID 26967565›Full record

ArticleOncotarget2016

Pre-treatment evaluation of 5-fluorouracil degradation rate: association of poor and ultra-rapid metabolism with severe toxicity in a colorectal cancer patients cohort.

Federica Mazzuca, Marina Borro, Andrea Botticelli, Eva Mazzotti, Luca Marchetti, Giovanna Gentile, Marco La Torre, Luana Lionetto, Maurizio Simmaco, Paolo Marchetti

Open access · diamondAbstract readEvaluation Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.7field-weighted citation impact, top 14% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

14 citing papers in PubMed, 24 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 5 institutions in 1 country.

Federica MazzucaOncology Unit, Sant'Andrea Hospital, Rome, Italy.
Marina BorroDepartment of Neurosciences, Mental Health and Sensory Organs (NESMOS), Sapienza University of Rome, Rome, Italy.
Andrea BotticelliDepartment of Clinical and Molecular Medicine, Sapienza University of Rome, Rome, Italy.
Eva MazzottiDepartment of Clinical and Molecular Medicine, Sapienza University of Rome, Rome, Italy.
Luca MarchettiDepartment of Clinical Oncology, Policlinico Umberto I, Rome, Italy.
Giovanna GentileIstituto Dermopatico dell'Immacolata-IRCCS, Rome, Italy.
Marco La TorreDepartment of Clinical Oncology, Policlinico Umberto I, Rome, Italy.
Luana LionettoIstituto Dermopatico dell'Immacolata-IRCCS, Rome, Italy.
Maurizio SimmacoDepartment of Neurosciences, Mental Health and Sensory Organs (NESMOS), Sapienza University of Rome, Rome, Italy.
Paolo MarchettiOncology Unit, Sant'Andrea Hospital, Rome, Italy.
Sapienza University of Rome · ITPoliclinico Umberto I · ITCTO Andrea Alesini · ITIstituti di Ricovero e Cura a Carattere Scientifico · ITIstituto Dermopatico dell'Immacolata · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Despite the wide use of 5-fluorouracil-based chemotherapy, development of severe toxicity that follow the treatment is not a rare event. The efforts to establish pretreatment tools for toxicity prediction, led to the development of various pharmacogenetic and biochemical assays, mainly targeted to assess the activity level of dihydropyrimidine dehydrogenase (DPD), the main metabolizing enzyme for 5-fluorouracil. Using peripheral blood mononuclear cells, we developed a biochemical assay, that is not limited to the evaluation of DPD activity, but determines the net result of all the enzymatic transformation of 5FU, in terms of the amount of drug consumed by the cells in a time unit. This parameter, named 5-fluorauracil degradation rate, presents a normal distribution inside the population and highlight the presence of an ultra-rapid metabolizers class of subjects, besides the expected poor metabolizers class. Here we will show that, in a colorectal cancer patient cohort, both poor and ultra-rapid metabolizers have significantly increased the risk of developing severe toxicity (grade3-4). Patient stratification depending on the individual 5-fluorouracil degradation rate allows to identify a 10% of the overall population at high risk of developing severe toxicity, compared to the 1.3% (as assessed in the Italian population) identified by the most commonly employed pharmacogenetic test, including the DPD polymorphism IVS14+1G>A.

Indexed as

Antimetabolites, AntineoplasticBiomarkers, TumorColorectal NeoplasmsDihydrouracil Dehydrogenase (NADP)FemaleFluorouracilFollow-Up StudiesHumansLeukocytes, MononuclearMaleMethylenetetrahydrofolate Reductase (NADPH2)Middle AgedPolymorphism, GeneticPrognosisThymidylate SynthaseAntimetabolites, AntineoplasticBiomarkers, TumorDihydrouracil Dehydrogenase (NADP)FluorouracilMethylenetetrahydrofolate Reductase (NADPH2)MTHFR protein, humanThymidylate SynthaseTYMS protein, human5-fluorouracil degradation ratecolorectal cancerDPYDfluorouracil toxicity predictionpolymorphisms

Identifiers

PMID26967565
PMCPMC4991479
OpenAlexW2296031291

What OpenQuestion holds

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Registered trials

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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.