Pazopanib may reduce bleeding in hereditary hemorrhagic telangiectasia
Document Type
Article
Abstract
© 2018, The Author(s). 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 There were 19 adverse events (AE) including one severe AE (elevated LFTs, withdrawn from dosing at 43 days); with no serious AE.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
Publication Date
2-15-2019
Publication Title
Angiogenesis
ISSN
09696970
E-ISSN
15737209
Volume
22
Issue
1
First Page
145
Last Page
155
PubMed ID
30191360
Digital Object Identifier (DOI)
10.1007/s10456-018-9646-1
Recommended Citation
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; and Sprecher, Dennis L., "Pazopanib may reduce bleeding in hereditary hemorrhagic telangiectasia" (2019). Translational Neuroscience. 648.
https://scholar.barrowneuro.org/neurobiology/648