Evidence map›Paper›PMID 24637941›Full record

Trial reportClinical pharmacology and therapeutics2014

Sorafenib dose escalation is not uniformly associated with blood pressure elevations in normotensive patients with advanced malignancies.

S Karovic, Y Wen, T G Karrison, G L Bakris, M R Levine, L K House, K Wu, V Thomeas, M A Rudek, J J Wright and 4 more

Open access · bronzeAbstract readRandomized Controlled Trial
In one paragraph

Trial report in Clinical pharmacology and therapeutics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
2.8field-weighted citation impact, top 10% 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

6 citing papers in PubMed, 12 citations in OpenAlex.

  1. Trial
  2. Article
  3. Article
  4. PharmGKB summary: sorafenib pathways.Pharmacogenetics and genomics · 2017
    Review
  5. Article
  6. Identification of a variant in KDR associated with serum VEGFR2 and pharmacodynamics of Pazopanib.Clinical cancer research : an official journal of the American Association for Cancer Research · 2015
    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

14 authors at 3 institutions in 1 country.

S KarovicSection of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, Illinois, USA.
Y WenCommittee on Clinical Pharmacology and Pharmacogenomics, The University of Chicago, Chicago, Illinois, USA.
T G Karrison1] Comprehensive Cancer Center, The University of Chicago, Chicago, Illinois, USA [2] Department of Health Studies, The University of Chicago, Chicago, Illinois, USA.
G L Bakris1] Committee on Clinical Pharmacology and Pharmacogenomics, The University of Chicago, Chicago, Illinois, USA [2] Section of Endocrinology, Diabetes, and Metabolism, Department of Medicine, The University of Chicago, Chicago, Illinois, USA.
M R LevineSection of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, Illinois, USA.
L K HouseSection of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, Illinois, USA.
K WuSection of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, Illinois, USA.
V ThomeasSection of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, Illinois, USA.
M A RudekThe Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland, USA.
J J WrightCancer Therapy Evaluation Program, National Cancer Institute, Rockville, Maryland, USA.
E E W Cohen1] Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, Illinois, USA [2] Comprehensive Cancer Center, The University of Chicago, Chicago, Illinois, USA.
G F Fleming1] Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, Illinois, USA [2] Committee on Clinical Pharmacology and Pharmacogenomics, The University of Chicago, Chicago, Illinois, USA [3] Comprehensive Cancer Center, The University of Chicago, Chicago, Illinois, USA.
M J Ratain1] Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, Illinois, USA [2] Committee on Clinical Pharmacology and Pharmacogenomics, The University of Chicago, Chicago, Illinois, USA [3] Comprehensive Cancer Center, The University of Chicago, Chicago, Illinois, USA.
M L Maitland1] Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, Illinois, USA [2] Committee on Clinical Pharmacology and Pharmacogenomics, The University of Chicago, Chicago, Illinois, USA [3] Comprehensive Cancer Center, The University of Chicago, Chicago, Illinois, USA.
University of Chicago · USNational Cancer Institute · USSidney Kimmel Comprehensive Cancer Center · US

Funding

Translational Research Central ServicesP30CA006973 · NCI · JOHNS HOPKINS UNIVERSITY · PI WILLIAM George NELSON · 1985 to 2026
$208.6M
Institute for Clinical and Translational Research (UL1)UL1RR025005 · NCRR · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2007 to 2011
$75.8M
Institute for Clinical and Translational ResearchUL1TR001079 · NCATS · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2013 to 2017
$60.1M
Whole GenomeU01GM061393 · NIGMS · UNIVERSITY OF CHICAGO · PI RATAIN, MARK J · 2000 to 2014
$39.0M
The Johns Hopkins Translational Science Team for the ET-CTNUM1CA186691 · NCI · JOHNS HOPKINS UNIVERSITY · PI Jan Hendrik Beumer, Michael A Carducci · 2014 to 2026
$21.9M
PHASE I CLINICAL TRIALS OF ANTICANCER AGENTSU01CA069852 · NCI · UNIVERSITY OF CHICAGO · PI RATAIN, MARK J · 1995 to 2013
$9.4M
Wisconsin and New Jersey Alliance in Precision Experimental TherapeuticsUM1CA186716 · NCI · RBHS -CANCER INSTITUTE OF NEW JERSEY · PI JABBOUR, SALMA, LIU, GLENN · 2014 to 2019
$4.1M
Experimental Therapeutics: Clinical Trials Network with Phase I EmphasisUM1CA186705 · NCI · UNIVERSITY OF CHICAGO · PI MAITLAND, MICHAEL L., RATAIN, MARK J · 2014 to 2015
$987k
Translational Medicine and Cancer Therapy with Vasculature-Targeted AgentsK23CA124802 · NCI · UNIVERSITY OF CHICAGO · PI MAITLAND, MICHAEL L. · 2007 to 2011
$649k
UPLC with Tandem MS for Sensitive Quantitative Analysis of Small MoleculesS10RR026824 · NCRR · JOHNS HOPKINS UNIVERSITY · PI RUDEK, MICHELLE A · 2010 to 2010
$429k
NCATS NIH HHS UL1 TR001079NCI NIH HHS K23 CA124802NCI NIH HHS P30 CA006973NCI NIH HHS U01 CA069852NCI NIH HHS UM1 CA186691NCI NIH HHS UM1 CA186705NCI NIH HHS UM1 CA186716NCRR NIH HHS S10 RR026824NCRR NIH HHS UL1 RR025005NIGMS NIH HHS U01 GM061393
6 · The paper itself

Abstract

Hypertension after treatment with vascular endothelial growth factor (VEGF) receptor inhibitors is associated with superior treatment outcomes for advanced cancer patients. To determine whether increased sorafenib doses cause incremental increases in blood pressure (BP), we measured 12-h ambulatory BP in 41 normotensive advanced solid tumor patients in a randomized dose-escalation study. After 7 days' treatment (400 mg b.i.d.), mean diastolic BP (DBP) increased in both study groups. After dose escalation, group A (400 mg t.i.d.) had marginally significant further increase in 12-h mean DBP (P = 0.053), but group B (600 mg b.i.d.) did not achieve statistically significant increases (P = 0.25). Within groups, individuals varied in BP response to sorafenib dose escalation, but these differences did not correlate with changes in steady-state plasma sorafenib concentrations. These findings in normotensive patients suggest BP is a complex pharmacodynamic biomarker of VEGF inhibition. Patients have intrinsic differences in sensitivity to sorafenib's BP-elevating effects.

Indexed as

AdultAgedBlood PressureDose-Response Relationship, DrugFemaleHumansMaleMiddle AgedNeoplasm MetastasisNeoplasmsNiacinamidePhenylurea CompoundsProspective StudiesReceptors, Vascular Endothelial Growth FactorSorafenibYoung AdultNiacinamidePhenylurea CompoundsReceptors, Vascular Endothelial Growth FactorSorafenib

Identifiers

PMID24637941
PMCPMC4165641
OpenAlexW2078330700

What OpenQuestion holds

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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.