Evidence map›Paper›PMID 24300978›Full record

ArticleBritish journal of cancer2014

SLC28A3 genotype and gemcitabine rate of infusion affect dFdCTP metabolite disposition in patients with solid tumours.

A Khatri, B W Williams, J Fisher, R C Brundage, V J Gurvich, L G Lis, K M Skubitz, A Z Dudek, E W Greeno, R A Kratzke and 2 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in British journal of cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed, 1 pooled it
2.2field-weighted citation impact, top 13% 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

16 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Clinical application and drug resistance mechanism of gemcitabine.Frontiers in cell and developmental biology · 2025
    Review
  5. Impact of genetic variants in the solute carrier (Cancer drug resistance (Alhambra, Calif.) · 2024
    Review
  6. Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Observational
  16. PharmGKB summary: gemcitabine pathway.Pharmacogenetics and genomics · 2014
    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

12 authors at 3 institutions in 1 country.

A KhatriDepartment of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, MN 55414, USA.
B W Williams1] Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, MN 55414, USA [2] Clinical Pharmacology Shared Resource of Masonic Comprehensive Cancer Center, University of Minnesota, Minneapolis, MN 55414, USA.
J Fisher1] Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, MN 55414, USA [2] Clinical Pharmacology Shared Resource of Masonic Comprehensive Cancer Center, University of Minnesota, Minneapolis, MN 55414, USA.
R C BrundageDepartment of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, MN 55414, USA.
V J Gurvich1] Department of Medicinal Chemistry, College of Pharmacy, University of Minnesota, Minneapolis, MN 55414, USA [2] Institute for Therapeutics Discovery and Development, College of Pharmacy, University of Minnesota, Minneapolis, MN 55414, USA [3] Masonic Comprehensive Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA.
L G LisInstitute for Therapeutics Discovery and Development, College of Pharmacy, University of Minnesota, Minneapolis, MN 55414, USA.
K M Skubitz1] Masonic Comprehensive Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA [2] Department of Medicine, School of Medicine, University of Minnesota, Minneapolis, MN 55455, USA.
A Z Dudek1] Masonic Comprehensive Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA [2] Department of Medicine, School of Medicine, University of Minnesota, Minneapolis, MN 55455, USA.
E W Greeno1] Masonic Comprehensive Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA [2] Department of Medicine, School of Medicine, University of Minnesota, Minneapolis, MN 55455, USA.
R A Kratzke1] Masonic Comprehensive Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA [2] Department of Medicine, School of Medicine, University of Minnesota, Minneapolis, MN 55455, USA.
J K Lamba1] Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, MN 55414, USA [2] Masonic Comprehensive Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA [3] PUMA-Institute of Personalized Medicine, College of Pharmacy, University of Minnesota, Minneapolis, MN 55455, USA.
M N Kirstein1] Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, MN 55414, USA [2] Clinical Pharmacology Shared Resource of Masonic Comprehensive Cancer Center, University of Minnesota, Minneapolis, MN 55414, USA [3] Masonic Comprehensive Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA [4] PUMA-Institute of Personalized Medicine, College of Pharmacy, University of Minnesota, Minneapolis, MN 55455, USA.
University of Minnesota · USUniversity of Minnesota Medical Center · USInnovative Design Labs (United States) · US

Funding

Women's CancerP30CA077598 · NCI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI Douglas Yee · 1998 to 2026
$100.4M
Pharmacogenomics of Ara-C in AMLR01CA132946 · NCI · UNIVERSITY OF MINNESOTA · PI LAMBA, JATINDER K., POUNDS, STANLEY BARRETT · 2008 to 2025
$5.3M
NCI NIH HHS 5P30 CA77598NCI NIH HHS P30 CA077598NCI NIH HHS R01 CA132946NCI NIH HHS R01CA132946
6 · The paper itself

Abstract

backgroundGemcitabine is used for the treatment of several solid tumours and exhibits high inter-individual pharmacokinetic variability. In this study, we explore possible predictive covariates on drug and metabolite disposition.

methodsForty patients were enrolled. Gemcitabine and dFdU concentrations in the plasma and dFdCTP concentrations in peripheral blood mononuclear cell were measured to 72 h post infusion, and pharmacokinetic parameters were estimated by nonlinear mixed-effects modelling. Patient-specific covariates were tested in model development.

resultsThe pharmacokinetics of gemcitabine was best described by a two-compartment model with body surface area, age and NT5C2 genotype as significant covariates. The pharmacokinetics of dFdU and dFdCTP were adequately described by three-compartment models. Creatinine clearance and cytidine deaminase genotype were significant covariates for dFdU pharmacokinetics. Rate of infusion of <25 mg m(-2) min(-1) and the presence of homozygous major allele for SLC28A3 (CC genotype) were each associated with an almost two-fold increase in the formation clearance of dFdCTP.

conclusionProlonged dFdCTP systemic exposures (≥72 h) were commonly observed. Infusion rate <25 mg m(-2) min(-1) and carriers for SLC28A3 variant were each associated with about two-fold higher dFdCTP formation clearance. The impacts of these covariates on treatment-related toxicity in more selected patient populations (that is, first-line treatment, single disease state and so on) are not yet clear.

Indexed as

5'-NucleotidaseAdultAgedAged, 80 and overAllelesAntimetabolites, AntineoplasticCytidine DeaminaseDeoxycytidineFemaleGemcitabineGenotypeHumansInfusions, IntravenousLeukocytes, MononuclearMaleMembrane Transport Proteins5'-NucleotidaseAntimetabolites, Antineoplasticcif nucleoside transporterCytidine DeaminaseDeoxycytidineGemcitabineMembrane Transport ProteinsNT5C2 protein, human

Identifiers

PMID24300978
PMCPMC3899768
OpenAlexW2089426557

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.