Evidence map›Paper›PMID 17605814›Full record

Trial reportJournal of translational medicine2007

Circulating protein biomarkers of pharmacodynamic activity of sunitinib in patients with metastatic renal cell carcinoma: modulation of VEGF and VEGF-related proteins.

Samuel E Deprimo, Carlo L Bello, John Smeraglia, Charles M Baum, Dominic Spinella, Brian I Rini, M Dror Michaelson, Robert J Motzer

Open access · goldAbstract readClinical Trial, Phase II
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Journal of translational medicine, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 133 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
133citing papers in PubMed, 1 pooled it
21.7field-weighted citation impact, top 1% 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

133 citing papers in PubMed, 1 synthesis or guideline pooled it, 320 citations in OpenAlex.

  1. Prognostic factors in renal cell carcinoma.World journal of urology · 2010
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  19. Plasma biomarkers as predictors of outcome in patients with advanced hepatocellular carcinoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2012
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73 more citing papers are in PubMed but not listed here.

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

8 authors at 4 institutions in 1 country.

Samuel E DeprimoTranslational Medicine, Pfizer Global Research and Development, La Jolla, CA, USA. sam.deprimo@pfizer.com
Carlo L Bello
John Smeraglia
Charles M Baum
Dominic Spinella
Brian I Rini
M Dror Michaelson
Robert J Motzer
Pfizer (United States) · USMassachusetts General Hospital · USMemorial Sloan Kettering Cancer Center · USUniversity of California, San Francisco · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundSunitinib malate (SUTENT) is an oral, multitargeted tyrosine kinase inhibitor, approved multinationally for the treatment of advanced RCC and of imatinib-resistant or - intolerant GIST. The purpose of this study was to explore potential biomarkers of sunitinib pharmacological activity via serial assessment of plasma levels of four soluble proteins from patients in a phase II study of advanced RCC: VEGF, soluble VEGFR-2 (sVEGFR-2), placenta growth factor (PlGF), and a novel soluble variant of VEGFR-3 (sVEGFR-3).

methodsSunitinib was administered at 50 mg/day on a 4/2 schedule (4 weeks on treatment, 2 weeks off treatment) to 63 patients with metastatic RCC after failure of first-line cytokine therapy. Predose plasma samples were collected on days 1 and 28 of each cycle and analyzed via ELISA.

resultsAt the end of cycle 1, VEGF and PlGF levels increased >3-fold (relative to baseline) in 24/54 (44%) and 22/55 (40%) cases, respectively (P < 0.001). sVEGFR-2 levels decreased >or= 30% in 50/55 (91%) cases and >or= 20% in all cases (P < 0.001) during cycle 1, while sVEGFR-3 levels were decreased >or= 30% in 48 of 55 cases (87%), and >or= 20% in all but 2 cases. These levels tended to return to near-baseline after 2 weeks off treatment, indicating that these effects were dependent on drug exposure. Overall, significantly larger changes in VEGF, sVEGFR-2, and sVEGFR-3 levels were observed in patients exhibiting objective tumor response compared with those exhibiting stable disease or disease progression (P < 0.05 for each analyte; analysis not done for PlGF).

conclusionSunitinib treatment in advanced RCC patients leads to modulation of plasma levels of circulating proteins involved in VEGF signaling, including soluble forms of two VEGF receptors. This panel of proteins may be of value as biomarkers of the pharmacological and clinical activity of sunitinib in RCC, and of angiogenic processes in cancer and other diseases.

Indexed as

Antineoplastic AgentsBiomarkers, TumorCarcinoma, Renal CellCluster AnalysisHumansIndolesKidney NeoplasmsMembrane ProteinsMiddle AgedNeoplasm ProteinsPyrrolesSolubilitySunitinibTime FactorsVascular Endothelial Growth Factor Receptor-2Vascular Endothelial Growth Factor Receptor-3Antineoplastic AgentsBiomarkers, TumorIndolesMembrane ProteinsNeoplasm ProteinsPIGF protein, humanPyrrolesSunitinibVascular Endothelial Growth Factor Receptor-2Vascular Endothelial Growth Factor Receptor-3Vascular Endothelial Growth Factors

Identifiers

PMID17605814
PMCPMC1939830
OpenAlexW2150452646

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.