Evidence map›Paper›PMID 25344452›Full record

Trial reportInvestigational new drugs2015

Role of the lean body mass and of pharmacogenetic variants on the pharmacokinetics and pharmacodynamics of sunitinib in cancer patients.

C Narjoz, A Cessot, A Thomas-Schoemann, J L Golmard, O Huillard, P Boudou-Rouquette, A Behouche, F Taieb, J P Durand, A Dauphin and 7 more

Abstract readClinical Trial
PubMed Publisher
In one paragraph

Trial report in Investigational new drugs, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed, 2 pooled it
3.7field-weighted citation impact, top 6% 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

25 citing papers in PubMed, 2 syntheses or guidelines pooled it, 50 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

17 authors at 8 institutions in 1 country.

C NarjozAssistance Publique Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Service de Biochimie, Unité Fonctionnelle de Pharmacogénétique et Oncologie Moléculaire, Paris, France.
A Cessot
A Thomas-Schoemann
J L Golmard
O Huillard
P Boudou-Rouquette
A Behouche
F Taieb
J P Durand
A Dauphin
R Coriat
M Vidal
M Tod
J Alexandre
M A Loriot
F Goldwasser
B Blanchet
Assistance Publique – Hôpitaux de Paris · FRDélégation Paris 5 · FRHôpital Cochin · FRSorbonne Paris Cité · FRHôpital Européen Georges-Pompidou · FRHôpital Européen · FRHospices Civils de Lyon · FRSorbonne Université · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionSunitinib is a multikinase inhibitor active in various cancers types including renal cancers and endocrine tumors. The study analyzed the influence of the lean body mass (LBM) and of pharmacogenetic variants on the exposure to sunitinib and its active metabolite, SU12662, and on sunitinib toxicity and clinical activity. MATERIALS AND

methodsExposure to sunitinib and SU12662 was assessed on days 10 and 21 during the first treatment cycle. Acute toxicity was graded using the NCI 4.0 CTCAE ver. 4.0. The LBM and 14 common single nucleotide polymorphisms in the CYP3A4/3A5, NR1I2, NR1I3, ABCB1, and ABCG2 genes were analyzed according to the drug exposure at day 10. Determinants (including sunitinib exposure and pharmacogenetic variants) for toxicities were assessed, as well as the relationship between drug exposure and survival in renal cancer patients.

resultsNinety-two patients (60 % with renal cancer) were assessable for pharmacokinetics, toxicity and survival, and 66 for genetic analysis. The LBM (p < 0.0001) and a polymorphism in the ABCG2 transporter (421C>A) (p = 0.014) were two independent parameters accounting for the variability of composite (sunitinib + SU12662) exposure. Advanced age (OR = 1.47 [1.01-2.15], p = 0.048) and high sunitinib exposure (OR = 1.16 [1.05-1.28], p = 0.005) were independently associated with any grade ≥ 3 acute toxicity, and high SU12662 exposure was associated with grade ≥ 2 thrombocytopenia (OR = 1.27 [1.03-1.57], p = 0.028). A high composite area under the curve (AUC) >1,973 ng/mL∙h at day 21 was associated with a doubled survival (35.2 vs 16.7 months; log-rank p = 0.0051) in renal cancer patients.

conclusionsThis study indicates that LBM and drug monitoring may be helpful in the management of sunitinib-treated patients.

Indexed as

Angiogenesis InhibitorsBody WeightIndolesProtein Kinase InhibitorsPyrrolesAgedATP-Binding Cassette TransportersATP Binding Cassette Transporter, Subfamily BATP Binding Cassette Transporter, Subfamily G, Member 2Constitutive Androstane ReceptorCytochrome P-450 CYP3AFemaleHumansMaleMiddle AgedNeoplasm ProteinsABCB1 protein, humanABCG2 protein, humanAngiogenesis InhibitorsATP-Binding Cassette TransportersATP Binding Cassette Transporter, Subfamily BATP Binding Cassette Transporter, Subfamily G, Member 2Constitutive Androstane ReceptorCYP3A4 protein, humanCYP3A5 protein, humanCytochrome P-450 CYP3AIndolesNeoplasm ProteinsNR1I3 protein, humanProtein Kinase InhibitorsPyrrolesReceptors, SteroidSU 12662Sunitinib

Identifiers

PMID25344452
OpenAlexW1984840953

What OpenQuestion holds

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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.