Evidence map›Paper›PMID 18797458›Full record

Trial reportBritish journal of cancer2008

Pharmacokinetic and pharmacogenetic determinants of the activity and toxicity of irinotecan in metastatic colorectal cancer patients.

E Rouits, V Charasson, A Pétain, M Boisdron-Celle, J-P Delord, M Fonck, A Laurand, A-L Poirier, A Morel, E Chatelut and 2 more

Registry-linked trialOpen access · hybridAbstract readClinical Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in British journal of cancer, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00559741 (Phase 2 Study to Improve Tolerance of Chemotherapy Involving Cetuximab and Multidrug FOLFIRI, With Pharmacokinetic and Pharmacogenetic Studies, in Patients With Metastatic Colorectal Cancer), which is not on this map. Cited by 24 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed, 3 pooled it
2.5field-weighted citation impact, top 11% 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.

NCT00559741 phase2completednot on this map

Phase 2 Study to Improve Tolerance of Chemotherapy Involving Cetuximab and Multidrug FOLFIRI, With Pharmacokinetic and Pharmacogenetic Studies, in Patients With Metastatic Colorectal Cancer

TypeinterventionalSponsorInstitut Cancerologie de l'OuestRan2005Enrolled80ConditionsColorectal CancerArmscetuximab, fluorouracil, irinotecan hydrochloride, leucovorin calcium, pharmacological study
3 · Its place in the literature

Who cites it

24 citing papers in PubMed, 3 syntheses or guidelines pooled it, 56 citations in OpenAlex.

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  20. Metabolic pathways of the camptothecin analog AR-67.Drug metabolism and disposition: the biological fate of chemicals · 2011
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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

12 authors at 4 institutions in 1 country.

E RouitsLaboratoire d'Oncopharmacologie, Centre Paul-Papin, 2 rue Moll, Angers 49000, France.
V Charasson
A Pétain
M Boisdron-Celle
J-P Delord
M Fonck
A Laurand
A-L Poirier
A Morel
E Chatelut
J Robert
E Gamelin
Centre Paul Broca · FRInstitut Bergonié · FRUniversité de Toulouse · FRInserm · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

This study aims at establishing relationships between genetic and non-genetic factors of variation of the pharmacokinetics of irinotecan and its metabolites; and also at establishing relationships between the pharmacokinetic or metabolic parameters and the efficacy and toxicity of irinotecan. We included 49 patients treated for metastatic colorectal cancer with a combination of 5-fluorouracil and irinotecan; a polymorphism in the UGT1A1 gene (TA repeat in the TATA box) and one in the CES2 gene promoter (830C>G) were studied as potential markers for SN-38 glucuronidation and irinotecan activation, respectively; and the potential activity of CYP3A4 was estimated from cortisol biotransformation into 6beta-hydroxycortisol. No pharmacokinetic parameter was directly predictive of clinical outcome or toxicity. The AUCs of three important metabolites of irinotecan, SN-38, SN-38 glucuronide and APC, were tentatively correlated with patients' pretreatment biological parameters related to drug metabolism (plasma creatinine, bilirubin and liver enzymes, and blood leukocytes). SN-38 AUC was significantly correlated with blood leukocytes number and SN-38G AUC was significantly correlated with plasma creatinine, whereas APC AUC was significantly correlated with plasma liver enzymes. The relative extent of irinotecan activation was inversely correlated with SN-38 glucuronidation. The TATA box polymorphism of UGT1A1 was significantly associated with plasma bilirubin levels and behaved as a significant predictor for neutropoenia. The level of cortisol 6beta-hydroxylation predicted for the occurrence of diarrhoea. All these observations may improve the routine use of irinotecan in colorectal cancer patients. UGT1A1 genotyping plus cortisol 6beta-hydroxylation determination could help to determine the optimal dose of irinotecan.

Indexed as

AdultAgedAntineoplastic Agents, PhytogenicArea Under CurveCamptothecinCarboxylesteraseChromatography, High Pressure LiquidColonic NeoplasmsFemaleGlucuronidesGlucuronosyltransferaseHumansIrinotecanMaleMiddle AgedPolymerase Chain Reaction7-ethyl-10-hydroxycamptothecin glucuronideAntineoplastic Agents, PhytogenicCamptothecinCarboxylesteraseCES2 protein, humanGlucuronidesGlucuronosyltransferaseIrinotecanUGT1A1 Enzyme

Identifiers

PMID18797458
PMCPMC2570505
OpenAlexW1967484119

What OpenQuestion holds

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Registered trials

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.