Evidence map›Paper›PMID 34480602›Full record

ArticleEuropean journal of clinical pharmacology2022

Evaluation of pharmacogenomics and hepatic nuclear imaging-related covariates by population pharmacokinetic models of irinotecan and its metabolites.

Zheng Liu, Jennifer H Martin, Winston Liauw, Sue-Anne McLachlan, Emma Link, Anetta Matera, Michael Thompson, Michael Jefford, Rod J Hicks, Carleen Cullinane and 8 more

Abstract read
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In one paragraph

Article in European journal of clinical pharmacology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.1field-weighted citation impact, top 56% 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

1 citing paper in PubMed, 1 citations in OpenAlex.

  1. 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

18 authors at 10 institutions in 1 country.

Zheng LiuSchool of Medicine and Public Health, University of Newcastle, Callaghan, NSW, Australia.
Jennifer H MartinSchool of Medicine and Public Health, University of Newcastle, Callaghan, NSW, Australia.
Winston LiauwDepartment of Medical Oncology, St. George's Hospital, Sydney, Australia.
Sue-Anne McLachlanDepartment of Medical Oncology, St. Vincent's Hospital, Melbourne, Australia.
Emma LinkBiostatistics and Clinical Trials Centre, Peter MacCallum Cancer Centre, Melbourne, Australia.
Anetta MateraBiostatistics and Clinical Trials Centre, Peter MacCallum Cancer Centre, Melbourne, Australia.
Michael ThompsonDepartment of Nuclear Medicine, Peter MacCallum Cancer Centre, Melbourne, Australia.
Michael JeffordDepartment of Oncology, Sir Peter MacCallum, University of Melbourne, Melbourne, Australia.
Rod J HicksDepartment of Oncology, Sir Peter MacCallum, University of Melbourne, Melbourne, Australia.
Carleen CullinaneDepartment of Oncology, Sir Peter MacCallum, University of Melbourne, Melbourne, Australia.
Athena HatzimihalisTranslational Research Laboratory, Peter MacCallum Cancer Centre, Melbourne, Australia.
Ian CampbellDepartment of Oncology, Sir Peter MacCallum, University of Melbourne, Melbourne, Australia.
Simone CrowleyPreviously Victorian Breast Cancer Research Cooperative (VBCRC) Cancer Genetics Laboratory, The Murdoch Children's Research Institute, The Royal Children's Hospital, Peter MacCallum Cancer Centre), MelbourneMelbourne, Australia.
Phillip J BealeDepartment of Medical Oncology, Concord and Royal Prince Alfred Hospital, Sydney, Australia.
Christos S KarapetisDepartment of Medical Oncology, Flinders Medical Centre, Flinders Centre for Innovation in Cancer, Adelaide, Australia.
Timothy PriceDepartment of Medical Oncology, The Queen Elizabeth Hospital, Adelaide, Australia.
Mathew E BurgeDepartment of Medical Oncology, Royal Brisbane and Women's Hospital, Brisbane, Australia.
Michael MichaelDepartment of Oncology, Sir Peter MacCallum, University of Melbourne, Melbourne, Australia. Michael.Michael@petermac.org.ORCID http://orcid.org/0000-0002-0593-2662
Peter MacCallum Cancer Centre · AUThe University of Melbourne · AUFlinders Medical Centre · AUQueen Elizabeth Hospital · AURoyal Brisbane and Women's Hospital · AURoyal Children's Hospital · AURoyal Prince Alfred Hospital · AUSt George Hospital · AUSt Vincent's Hospital Melbourne · AUUniversity of Newcastle Australia · AU

Funding

Cancer Council NSW N/ANational Health and Medical Research Council Grant No. 628564
6 · The paper itself

Abstract

backgroundBody surface area (BSA)-based dosing of irinotecan (IR) does not account for its pharmacokinetic (PK) and pharmacodynamic (PD) variabilities. Functional hepatic nuclear imaging (HNI) and excretory/metabolic/PD pharmacogenomics have shown correlations with IR disposition and toxicity/efficacy. This study reports the development of a nonlinear mixed-effect population model to identify pharmacogenomic and HNI-related covariates that impact on IR disposition to support dosage optimization.

methodsPatients had advanced colorectal cancer treated with IR combination therapy. Baseline blood was analysed by Affymetrix DMET™ Plus Array and, for PD, single nucleotide polymorphisms (SNPs) by Sanger sequencing. For HNI, patients underwent

resultsAnalysis included (i) PK data: 32 patients; (ii) pharmacogenomic data: 31 patients: 750 DMET and 22 PD variants; and (iii) HNI data: 32 patients. On initial analysis, overall five SNPs were identified as significant covariates for CL

conclusionThe identified UGT1A3_c.31 T > C and ABCB1_c.3435C > T variants, from wild type to homozygous, were included in the final model for SN38 clearance.

Indexed as

Antineoplastic Combined Chemotherapy ProtocolsATP Binding Cassette Transporter, Subfamily BAustraliaColorectal NeoplasmsGenotypeGlucuronosyltransferaseHumansIrinotecanLiverModels, BiologicalNeoplasm MetastasisPharmacogeneticsPharmacogenomic VariantsPolymorphism, Single NucleotideProspective StudiesTopoisomerase I InhibitorsABCB1 protein, humanATP Binding Cassette Transporter, Subfamily BGlucuronosyltransferaseIrinotecanTopoisomerase I InhibitorsUDP-glucuronosyltransferase, UGT1A3DMETHepatic functional imagingIrinotecanPharmacodynamicsPharmacokineticsPopulation model

Identifiers

PMID34480602
OpenAlexW3197427958

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.