Evidence map›Paper›PMID 21131369›Full record

ArticleAnnals of oncology : official journal of the European Society for Medical Oncology2011

A phase I study to determine the safety, pharmacokinetics and pharmacodynamics of a dual VEGFR and FGFR inhibitor, brivanib, in patients with advanced or metastatic solid tumors.

D J Jonker, L S Rosen, M B Sawyer, F de Braud, G Wilding, C J Sweeney, G C Jayson, G A McArthur, G Rustin, G Goss and 8 more

Abstract readClinical Trial, Phase I
PubMed Full text at PMC Publisher
In one paragraph

Article in Annals of oncology : official journal of the European Society for Medical Oncology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
–field-weighted citation impact
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

33 citing papers in PubMed.

  1. Review
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  5. Article
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  8. Molecular targeted and immune checkpoint therapy for advanced hepatocellular carcinoma.Journal of experimental & clinical cancer research : CR · 2019
    Review
  9. Article
  10. Review
  11. Review
  12. Article
  13. Review
  14. Imaging biomarker roadmap for cancer studies.Nature reviews. Clinical oncology · 2017
    Review
  15. Review
  16. Roles of FGFR in oral carcinogenesis.Cell proliferation · 2016
    Review
  17. Article
  18. Article
  19. Review
  20. Review
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.

D J JonkerDivision of Medical Oncology, Ottawa Hospital Cancer Centre, University of Ottawa, Ottawa, Canada. Electronic address: djonker@ottawahospital.on.ca.
L S RosenDepartment of Oncology, Premiere Oncology, Santa Monica, USA.
M B SawyerDepartment of Oncology, Cross Cancer Institute, Edmonton, Canada.
F de BraudDivision of Clinical Pharmacology and New Drugs, Department of Medicine, European Institute of Oncology, Milan, Italy.
G WildingDepartment of Oncology, University of Wisconsin Carbone Cancer Center, Madison.
C J SweeneyDepartment of Medicine, Dana-Farber Cancer Institute, Boston, USA.
G C JaysonDepartment of Oncology, Christie Hospital, University of Manchester, Manchester, UK.
G A McArthurDepartment of Medical Oncology, Peter MacCallum Cancer Center, East Melbourne, Australia.
G RustinDepartment of Medical Oncology, Mount Vernon Cancer Centre, Northwood, Middlesex, UK.
G GossDivision of Medical Oncology, Ottawa Hospital Cancer Centre, University of Ottawa, Ottawa, Canada.
J KantorResearch and Development, Bristol-Myers Squibb, Princeton, USA.
L VelasquezResearch and Development, Bristol-Myers Squibb, Princeton, USA.
S SyedResearch and Development, Bristol-Myers Squibb, Princeton, USA.
O MokliatchoukResearch and Development, Bristol-Myers Squibb, Princeton, USA.
D M FeltquateResearch and Development, Bristol-Myers Squibb, Princeton, USA.
G KolliaResearch and Development, Bristol-Myers Squibb, Princeton, USA.
D S A NuytenResearch and Development, Bristol-Myers Squibb, Princeton, USA.
S GalbraithResearch and Development, Bristol-Myers Squibb, Princeton, USA.

Funding

NCI NIH HHS CA182002
6 · The paper itself

Abstract

backgroundThis study was designed to determine the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of brivanib in patients with advanced/metastatic solid tumors. PATIENTS AND

methodsNinety patients enrolled in this two-part, phase I open-label study of oral brivanib alaninate. The primary objectives of this study were (in part A) dose-limiting toxicity, maximum tolerated dose (MTD) and the lowest biologically active dose level and (in part B) the optimal dose/dose range. The secondary objectives of this study were preliminary evidence of antitumor activity, PK and PD.

resultsAcross part A (open-label dose escalation and MTD) and part B (open-label dose optimization), 68 patients received brivanib alaninate. Brivanib demonstrated a manageable toxicity profile at doses of 180-800 mg. Most toxic effects were mild. Systemic exposure of the active moiety brivanib increased linearly ≤1000 mg/day. The MTD was 800 mg/day. Forty-four patients were treated at the MTD: 20 with 800 mg continuously, 11 with 800 mg intermittently and 13 with 400 mg b.i.d. doses. Partial responses were confirmed in two patients receiving brivanib ≥600 mg. Dynamic contrast-enhanced magnetic resonance imaging demonstrated statistically significant decreases in parameters reflecting tumor vascularity and permeability after multiple doses in the 800-mg continuous q.d. and 400-mg b.i.d. dose cohorts.

conclusionIn patients with advanced/metastatic cancer, brivanib demonstrates promising antiangiogenic and antitumor activity and manageable toxicity at doses ≤800 mg orally q.d., the recommended phase II study dose.

Indexed as

AdultAgedAged, 80 and overAlanineAngiogenesis InhibitorsAntineoplastic AgentsDose-Response Relationship, DrugFemaleHumansMaleMaximum Tolerated DoseMiddle AgedNeoplasm MetastasisNeoplasmsNeovascularization, PathologicReceptors, Fibroblast Growth FactorAlanineAngiogenesis InhibitorsAntineoplastic AgentsbrivanibReceptors, Fibroblast Growth FactorReceptors, Vascular Endothelial Growth FactorTriazines

Identifiers

PMID21131369
PMCPMC3139984

What OpenQuestion holds

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Read underepoch 390

Registered trials

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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.