Evidence map›Paper›PMID 25047123›Full record

ArticleBMC cancer2014

Pharmacodynamic change in plasma angiogenic proteins: a dose-escalation phase 1 study of the multi-kinase inhibitor lenvatinib.

Noriyuki Koyama, Kenichi Saito, Yuki Nishioka, Wataru Yusa, Noboru Yamamoto, Yasuhide Yamada, Hiroshi Nokihara, Fumiaki Koizumi, Kazuto Nishio, Tomohide Tamura

Registry-linked trialAbstract readClinical Trial, Phase I
PubMed Full text at PMC Publisher
In one paragraph

Article in BMC cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00280397 (An Open Label Phase I Dose Escalation Study of E7080 Administered to Patients With Solid Tumors), which is not on this map. Cited by 23 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed, 2 pooled it
–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.

NCT00280397 phase1completednot on this map

An Open Label Phase I Dose Escalation Study of E7080 Administered to Patients With Solid Tumors

TypeinterventionalSponsorEisai Inc.Ran2006 to 2008Enrolled27ConditionsCancer: Solid TumorsArmsE7080
3 · Its place in the literature

Who cites it

23 citing papers in PubMed, 2 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Trial
  5. Review
  6. Review
  7. Article
  8. Article
  9. Review
  10. Review
  11. Review
  12. Review
  13. Review
  14. Observational
  15. Review
  16. Review
  17. Review
  18. Review
  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

10 authors.

Noriyuki Koyama
Kenichi Saito
Yuki Nishioka
Wataru Yusa
Noboru Yamamoto
Yasuhide Yamada
Hiroshi Nokihara
Fumiaki Koizumi
Kazuto Nishio
Tomohide TamuraDepartment of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan. ttamura@ncc.go.jp.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundLenvatinib (E7080), an oral multi-kinase inhibitor, has inhibitory action on tumor cell proliferation and tumor angiogenesis in preclinical models. We evaluated correlations between pharmacodynamic (PD) biomarkers with patient clinical outcomes in a lenvatinib phase 1 dose-escalation study.

methodsPlasma angiogenic proteins were evaluated as potential PD biomarkers of response to lenvatinib in a dose-escalation phase 1 study. Lenvatinib was administered to 27 patients by twice-daily dosing in 3-week cycles; 2 weeks of treatment followed by 1 week of rest until discontinuation. Blood samples for plasma proteins were collected on days 1 (baseline), 8, and 15 of cycle 1, and days 1, 8, and 15 of cycle 2. Selected clinical outcomes, including tumor shrinkage and adverse events (AEs), were used for correlative analyses of pharmacokinetic parameters and PD biomarkers.

resultsTumor shrinkage and changes in PD biomarkers (increased vascular endothelial growth factor [VEGF] and stromal cell-derived factor 1 alpha [SDF1α] levels and decreased soluble VEGF receptor 2 [sVEGFR2] levels) significantly correlated with increasing lenvatinib exposure. Observed changes in levels of VEGF, SDF1α, and sVEGFR2 were maintained on day 15 of cycle 1, but returned to baseline during the 1-week rest period, and similar changes were induced by reinstitution of treatment in cycle 2. The worst grades of hypertension, proteinuria, and fatigue were associated with changes in VEGF and HGF at day 8 of cycle 1. Maximum tumor shrinkage was correlated with increased SDF1α levels. Decreased sVEGFR2 level was also correlated with tumor shrinkage and frequency of hypertension, proteinuria, and fatigue. Tumor shrinkage significantly correlated with the worst grade of proteinuria, but not with hypertension or fatigue.

conclusionPD biomarker changes observed in plasma angiogenic proteins are correlated with lenvatinib-induced tumor shrinkage and AEs. Our findings warrant further assessment of plasma proteins associated with angiogenesis as potential biomarkers of lenvatinib activity.

trial registrationClinicalTrial.gov: NCT00280397 (January 20, 2006).

Indexed as

Angiogenic ProteinsBiomarkers, PharmacologicalBlood ProteinsDisease ProgressionDrug Administration ScheduleGene Expression Regulation, NeoplasticHumansNeoplasmsPhenylurea CompoundsProtein Kinase InhibitorsQuinolinesTreatment OutcomeAngiogenic ProteinsBiomarkers, PharmacologicalBlood ProteinslenvatinibPhenylurea CompoundsProtein Kinase InhibitorsQuinolines

Identifiers

PMID25047123
PMCPMC4223557

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.