Pazopanib may reduce bleeding in hereditary hemorrhagic telangiectasia

Marie E. Faughnan, James R Gossage, Murali M. Chakinala, S. Paul Oh, Raj Kasthuri, Christopher C.W. Hughes, Justin P. McWilliams, Joseph G. Parambil, Nicholas Vozoris, Jill Donaldson, Gitanjali Paul, Pamela Berry, Dennis L. Sprecher

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Pazopanib (Votrient) is an orally administered tyrosine kinase inhibitor that blocks VEGF receptors potentially serving as anti-angiogenic treatment for hereditary hemorrhagic telangiectasia (HHT). We report a prospective, multi-center, open-label, dose-escalating study [50 mg, 100 mg, 200 mg, and 400 mg], designed as a proof-of-concept study to demonstrate efficacy of pazopanib on HHT-related bleeding, and to measure safety. Patients, recruited at 5 HHT Centers, required ≥ 2 Curacao criteria AND [anemia OR severe epistaxis with iron deficiency]. Co-primary outcomes, hemoglobin (Hgb) and epistaxis severity, were measured during and after treatment, and compared to baseline. Safety monitoring occurred every 1.5 weeks. Seven patients were treated with 50 mg pazopanib daily. Six/seven showed at least 50% decrease in epistaxis duration relative to baseline at some point during study; 3 showed at least 50% decrease in duration during Weeks 11 and 12. Six patients showed a decrease in ESS of > 0.71 (MID) relative to baseline at some point during study; 3/6 showed a sustained improvement. Four patients showed > 2 gm improvement in Hgb relative to baseline at one or more points during study. Health-related QOL scores improved on all SF-36 domains at Week 6 and/or Week 12, except general health (unchanged). There were 19 adverse events (AE) including one severe AE (elevated LFTs, withdrawn from dosing at 43 days); with no serious AE. In conclusion, we observed an improvement in Hgb and/or epistaxis in all treated patients. This occurred at a dose much lower than typically used for oncologic indications, with no serious AE. Further studies of pazopanib efficacy are warranted.

Original languageEnglish (US)
Pages (from-to)145-155
Number of pages11
JournalAngiogenesis
Volume22
Issue number1
DOIs
StatePublished - Feb 15 2019

Fingerprint

Hereditary Hemorrhagic Telangiectasia
Epistaxis
Hemorrhage
Hemoglobins
Health
Safety
Vascular Endothelial Growth Factor Receptor
Netherlands
Protein-Tyrosine Kinases
Labels
Anemia
Iron
pazopanib
Monitoring
Therapeutics

Keywords

  • Anemia
  • Epistaxis
  • Hereditary
  • Telangiectasia
  • Tyrosine kinase inhibitor

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cancer Research

Cite this

Faughnan, M. E., Gossage, J. R., Chakinala, M. M., Oh, S. P., Kasthuri, R., Hughes, C. C. W., ... Sprecher, D. L. (2019). Pazopanib may reduce bleeding in hereditary hemorrhagic telangiectasia. Angiogenesis, 22(1), 145-155. https://doi.org/10.1007/s10456-018-9646-1

Pazopanib may reduce bleeding in hereditary hemorrhagic telangiectasia. / Faughnan, Marie E.; Gossage, James R; Chakinala, Murali M.; Oh, S. Paul; Kasthuri, Raj; Hughes, Christopher C.W.; McWilliams, Justin P.; Parambil, Joseph G.; Vozoris, Nicholas; Donaldson, Jill; Paul, Gitanjali; Berry, Pamela; Sprecher, Dennis L.

In: Angiogenesis, Vol. 22, No. 1, 15.02.2019, p. 145-155.

Research output: Contribution to journalArticle

Faughnan, ME, Gossage, JR, Chakinala, MM, Oh, SP, Kasthuri, R, Hughes, CCW, McWilliams, JP, Parambil, JG, Vozoris, N, Donaldson, J, Paul, G, Berry, P & Sprecher, DL 2019, 'Pazopanib may reduce bleeding in hereditary hemorrhagic telangiectasia', Angiogenesis, vol. 22, no. 1, pp. 145-155. https://doi.org/10.1007/s10456-018-9646-1
Faughnan ME, Gossage JR, Chakinala MM, Oh SP, Kasthuri R, Hughes CCW et al. Pazopanib may reduce bleeding in hereditary hemorrhagic telangiectasia. Angiogenesis. 2019 Feb 15;22(1):145-155. https://doi.org/10.1007/s10456-018-9646-1
Faughnan, Marie E. ; Gossage, James R ; Chakinala, Murali M. ; Oh, S. Paul ; Kasthuri, Raj ; Hughes, Christopher C.W. ; McWilliams, Justin P. ; Parambil, Joseph G. ; Vozoris, Nicholas ; Donaldson, Jill ; Paul, Gitanjali ; Berry, Pamela ; Sprecher, Dennis L. / Pazopanib may reduce bleeding in hereditary hemorrhagic telangiectasia. In: Angiogenesis. 2019 ; Vol. 22, No. 1. pp. 145-155.
@article{c6dee35332cd49d3a7c9cfc872e3165d,
title = "Pazopanib may reduce bleeding in hereditary hemorrhagic telangiectasia",
abstract = "Pazopanib (Votrient) is an orally administered tyrosine kinase inhibitor that blocks VEGF receptors potentially serving as anti-angiogenic treatment for hereditary hemorrhagic telangiectasia (HHT). We report a prospective, multi-center, open-label, dose-escalating study [50 mg, 100 mg, 200 mg, and 400 mg], designed as a proof-of-concept study to demonstrate efficacy of pazopanib on HHT-related bleeding, and to measure safety. Patients, recruited at 5 HHT Centers, required ≥ 2 Curacao criteria AND [anemia OR severe epistaxis with iron deficiency]. Co-primary outcomes, hemoglobin (Hgb) and epistaxis severity, were measured during and after treatment, and compared to baseline. Safety monitoring occurred every 1.5 weeks. Seven patients were treated with 50 mg pazopanib daily. Six/seven showed at least 50{\%} decrease in epistaxis duration relative to baseline at some point during study; 3 showed at least 50{\%} decrease in duration during Weeks 11 and 12. Six patients showed a decrease in ESS of > 0.71 (MID) relative to baseline at some point during study; 3/6 showed a sustained improvement. Four patients showed > 2 gm improvement in Hgb relative to baseline at one or more points during study. Health-related QOL scores improved on all SF-36 domains at Week 6 and/or Week 12, except general health (unchanged). There were 19 adverse events (AE) including one severe AE (elevated LFTs, withdrawn from dosing at 43 days); with no serious AE. In conclusion, we observed an improvement in Hgb and/or epistaxis in all treated patients. This occurred at a dose much lower than typically used for oncologic indications, with no serious AE. Further studies of pazopanib efficacy are warranted.",
keywords = "Anemia, Epistaxis, Hereditary, Telangiectasia, Tyrosine kinase inhibitor",
author = "Faughnan, {Marie E.} and Gossage, {James R} and Chakinala, {Murali M.} and Oh, {S. Paul} and Raj Kasthuri and Hughes, {Christopher C.W.} and McWilliams, {Justin P.} and Parambil, {Joseph G.} and Nicholas Vozoris and Jill Donaldson and Gitanjali Paul and Pamela Berry and Sprecher, {Dennis L.}",
year = "2019",
month = "2",
day = "15",
doi = "10.1007/s10456-018-9646-1",
language = "English (US)",
volume = "22",
pages = "145--155",
journal = "Angiogenesis",
issn = "0969-6970",
publisher = "Springer Netherlands",
number = "1",

}

TY - JOUR

T1 - Pazopanib may reduce bleeding in hereditary hemorrhagic telangiectasia

AU - Faughnan, Marie E.

AU - Gossage, James R

AU - Chakinala, Murali M.

AU - Oh, S. Paul

AU - Kasthuri, Raj

AU - Hughes, Christopher C.W.

AU - McWilliams, Justin P.

AU - Parambil, Joseph G.

AU - Vozoris, Nicholas

AU - Donaldson, Jill

AU - Paul, Gitanjali

AU - Berry, Pamela

AU - Sprecher, Dennis L.

PY - 2019/2/15

Y1 - 2019/2/15

N2 - Pazopanib (Votrient) is an orally administered tyrosine kinase inhibitor that blocks VEGF receptors potentially serving as anti-angiogenic treatment for hereditary hemorrhagic telangiectasia (HHT). We report a prospective, multi-center, open-label, dose-escalating study [50 mg, 100 mg, 200 mg, and 400 mg], designed as a proof-of-concept study to demonstrate efficacy of pazopanib on HHT-related bleeding, and to measure safety. Patients, recruited at 5 HHT Centers, required ≥ 2 Curacao criteria AND [anemia OR severe epistaxis with iron deficiency]. Co-primary outcomes, hemoglobin (Hgb) and epistaxis severity, were measured during and after treatment, and compared to baseline. Safety monitoring occurred every 1.5 weeks. Seven patients were treated with 50 mg pazopanib daily. Six/seven showed at least 50% decrease in epistaxis duration relative to baseline at some point during study; 3 showed at least 50% decrease in duration during Weeks 11 and 12. Six patients showed a decrease in ESS of > 0.71 (MID) relative to baseline at some point during study; 3/6 showed a sustained improvement. Four patients showed > 2 gm improvement in Hgb relative to baseline at one or more points during study. Health-related QOL scores improved on all SF-36 domains at Week 6 and/or Week 12, except general health (unchanged). There were 19 adverse events (AE) including one severe AE (elevated LFTs, withdrawn from dosing at 43 days); with no serious AE. In conclusion, we observed an improvement in Hgb and/or epistaxis in all treated patients. This occurred at a dose much lower than typically used for oncologic indications, with no serious AE. Further studies of pazopanib efficacy are warranted.

AB - Pazopanib (Votrient) is an orally administered tyrosine kinase inhibitor that blocks VEGF receptors potentially serving as anti-angiogenic treatment for hereditary hemorrhagic telangiectasia (HHT). We report a prospective, multi-center, open-label, dose-escalating study [50 mg, 100 mg, 200 mg, and 400 mg], designed as a proof-of-concept study to demonstrate efficacy of pazopanib on HHT-related bleeding, and to measure safety. Patients, recruited at 5 HHT Centers, required ≥ 2 Curacao criteria AND [anemia OR severe epistaxis with iron deficiency]. Co-primary outcomes, hemoglobin (Hgb) and epistaxis severity, were measured during and after treatment, and compared to baseline. Safety monitoring occurred every 1.5 weeks. Seven patients were treated with 50 mg pazopanib daily. Six/seven showed at least 50% decrease in epistaxis duration relative to baseline at some point during study; 3 showed at least 50% decrease in duration during Weeks 11 and 12. Six patients showed a decrease in ESS of > 0.71 (MID) relative to baseline at some point during study; 3/6 showed a sustained improvement. Four patients showed > 2 gm improvement in Hgb relative to baseline at one or more points during study. Health-related QOL scores improved on all SF-36 domains at Week 6 and/or Week 12, except general health (unchanged). There were 19 adverse events (AE) including one severe AE (elevated LFTs, withdrawn from dosing at 43 days); with no serious AE. In conclusion, we observed an improvement in Hgb and/or epistaxis in all treated patients. This occurred at a dose much lower than typically used for oncologic indications, with no serious AE. Further studies of pazopanib efficacy are warranted.

KW - Anemia

KW - Epistaxis

KW - Hereditary

KW - Telangiectasia

KW - Tyrosine kinase inhibitor

UR - http://www.scopus.com/inward/record.url?scp=85052968546&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85052968546&partnerID=8YFLogxK

U2 - 10.1007/s10456-018-9646-1

DO - 10.1007/s10456-018-9646-1

M3 - Article

C2 - 30191360

AN - SCOPUS:85052968546

VL - 22

SP - 145

EP - 155

JO - Angiogenesis

JF - Angiogenesis

SN - 0969-6970

IS - 1

ER -