Evidence map›Paper›PMID 30628113›Full record

ArticleBritish journal of clinical pharmacology2019

Open-label study to evaluate trifluridine/tipiracil safety, tolerability and pharmacokinetics in patients with advanced solid tumours and hepatic impairment.

Muhammad Wasif Saif, Lee Rosen, Michelle A Rudek, Weijing Sun, Dale R Shepard, Carlos Becerra, Fumiaki Yamashita, Paul Bebeau, Robert Winkler

Open access · bronzeAbstract readClinical Trial, Phase IMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in British journal of clinical pharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.6field-weighted citation impact, top 30% 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

2 citing papers in PubMed, 9 citations in OpenAlex.

  1. Trial
  2. Article
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

9 authors at 7 institutions in 1 country.

Muhammad Wasif SaifNorthwell Health Cancer Institute, Lake Success, NY, USA.ORCID 0000-0001-8154-957X
Lee RosenUniversity of California, Los Angeles, CA, USA.
Michelle A RudekJohns Hopkins University, Baltimore, MD, USA.
Weijing SunUniversity of Kansas, Kansas City, KS, USA.
Dale R ShepardCleveland Clinic, Cleveland, OH, USA.
Carlos BecerraTexas Oncology, Baylor University Medical Center, Dallas, TX, USA.
Fumiaki YamashitaTaiho Oncology, Inc, Princeton, NJ, USA.
Paul BebeauTaiho Oncology, Inc, Princeton, NJ, USA.
Robert WinklerTaiho Oncology, Inc, Princeton, NJ, USA.
Taiho Oncology (United States) · USCleveland Clinic · USJohns Hopkins University · USNorthwell Health · USTexas Oncology · USUniversity of California, Los Angeles · USUniversity of Kansas · US

Funding

Translational Research Central ServicesP30CA006973 · NCI · JOHNS HOPKINS UNIVERSITY · PI Rosalie Wollett · 1985 to 2026
$208.6M
NCI NIH HHS P30 CA006973
6 · The paper itself

Abstract

aimsTrifluridine/tipiracil (FTD/TPI) prolongs survival in refractory metastatic colorectal cancer, but limited data exist on its use in patients with hepatic impairment. This Phase I, open-label, nonrandomized study investigated the safety, tolerability and pharmacokinetics of FTD/TPI in patients with advanced solid tumours (except breast cancer) and varying degrees of hepatic impairment, to provide dosing recommendations.

methodsPatients aged ≥18 years with advanced solid tumours and normal hepatic function, or mild, moderate or severe hepatic impairment according to National Cancer Institute criteria, were planned to be enrolled. Patients received FTD/TPI 35 mg/m

resultsTwenty-four patients were enrolled to the normal hepatic function (n = 8) and mild (n = 10) and moderate (n = 6) hepatic impairment cohorts. Overall, 12 patients (50.0%) had at least 1 adverse event leading to study discontinuation. In the moderate hepatic impairment cohort, 5 of 6 patients experienced grade ≥ 3 elevation in bilirubin. No patients with severe hepatic impairment were enrolled. FTD area under the curve at steady state decreased by 18% and 22% in the mild and moderate cohorts, respectively; however, no clear change was observed in TPI area under the curve.

conclusionsFTD/TPI can be safely administered in patients with normal hepatic function and mild hepatic impairment, with no initial dose adjustment. FTD/TPI is not recommended for use in patients with moderate hepatic impairment because of findings of grade 3 or 4 increased blood bilirubin. Therefore, FTD/TPI is not recommended for patients with moderate or severe hepatic impairment.

Indexed as

Administration, OralAdultAgedAntineoplastic AgentsBilirubinDrug Administration ScheduleDrug CombinationsDrug Dosage CalculationsFemaleHumansLiverLiver DiseasesMaleMiddle AgedModels, BiologicalNeoplasmsAntineoplastic AgentsBilirubinDrug CombinationsPyrrolidinesThymineTrifluridinetrifluridine tipiracil drug combinationUracilchemotherapydrug developmentgastroenterologyliveroncologypharmacokineticsphase I

Identifiers

PMID30628113
PMCPMC6533429
OpenAlexW2910801995

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.