pazopanib has been researched along with Telangiectasia--Hereditary-Hemorrhagic* in 6 studies
1 trial(s) available for pazopanib and Telangiectasia--Hereditary-Hemorrhagic
Article | Year |
---|---|
Pazopanib may reduce bleeding in hereditary hemorrhagic telangiectasia.
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 There were 19 adverse events (AE) including one severe AE (elevated LFTs, withdrawn from dosing at 43 days); with no serious AE.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. Topics: Adult; Female; Hemorrhage; Humans; Indazoles; Male; Middle Aged; Pyrimidines; Sulfonamides; Telangiectasia, Hereditary Hemorrhagic | 2019 |
5 other study(ies) available for pazopanib and Telangiectasia--Hereditary-Hemorrhagic
Article | Year |
---|---|
Improvement of Cutaneous Hereditary Hemorrhagic Telangiectasia With Pazopanib-A Multikinase Inhibitor.
Topics: Humans; Indazoles; Pyrimidines; Sulfonamides; Telangiectasia, Hereditary Hemorrhagic | 2022 |
Pazopanib for severe bleeding and transfusion-dependent anemia in hereditary hemorrhagic telangiectasia.
Hereditary hemorrhagic telangiectasia (HHT) is a rare angiogenic disorder causing chronic gastrointestinal bleeding, epistaxis, and severe anemia. Pazopanib is an oral multi-kinase angiogenesis inhibitor with promise to treat bleeding in HHT. We analyzed outcomes of HHT patients with the most severe bleeding causing RBC transfusion dependence treated on a predefined institutional pazopanib treatment pathway (with data collected retrospectively). The primary endpoint was achievement of transfusion independence. Secondary endpoints included hemoglobin, epistaxis severity score, RBC transfusion and iron infusion requirements, number of local hemostatic procedures, ferritin and transferrin saturation, compared using paired and repeated measures mean tests. Thirteen transfusion-dependent HHT patients received pazopanib [median (range) dose 150 (25-300) mg daily)] for a median of 22 months. All patients achieved transfusion independence. Compared with pretreatment, pazopanib increased mean hemoglobin by 4.8 (95% CI, 3.6-5.9) g/dL (7.8 vs. 12.7 g/dL, P < 0.0001) and decreased mean epistaxis severity score by 4.77 (3.11-6.44) points (7.20 vs. 2.43 points, P < 0.0001) after 12 months of treatment. Compared with 3 months of pretreatment, RBC transfusions decreased by 93% (median of 16.0 vs. 0.0 units, P < 0.0001) and elemental iron infusion decreased by 92% (median of 4500 vs. 0 mg, P = 0.005) during the first 3 months of treatment; improvements were maintained over time. Pazopanib was well-tolerated: hypertension, lymphocytopenia, and fatigue were the most common TEAEs. In conclusion, pazopanib was safe and effective to manage severe bleeding in HHT, liberating all patients from transfusion dependence and normalizing hematologic parameters at doses lower than used to treat malignancies. These findings require confirmation in a randomized trial. Topics: Anemia; Epistaxis; Humans; Indazoles; Pyrimidines; Retrospective Studies; Sulfonamides; Telangiectasia, Hereditary Hemorrhagic | 2022 |
EHA 2021 Virtual Congress.
Topics: Activin Receptors, Type II; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; beta-Thalassemia; Graft vs Host Disease; Hematologic Diseases; Humans; Immunoglobulin Fc Fragments; Indazoles; Interleukin-1 Receptor-Associated Kinases; Internet; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Myeloid, Acute; Lymphoma, B-Cell; Multiple Myeloma; Protein Kinase Inhibitors; Pyrimidines; Recombinant Fusion Proteins; Sulfonamides; Telangiectasia, Hereditary Hemorrhagic | 2021 |
Pazopanib effective for bevacizumab-unresponsive epistaxis in hereditary hemorrhagic telangiectasia.
Hereditary hemorrhagic telangiectasia (HHT) most commonly manifests with nasal mucosal telangiectasias, and vascular endothelial growth factor (VEGF) plays a significant role in this angiodysplasia. We describe a patient with HHT with epistaxis recalcitrant to several endonasal procedures and six cycles of intravenous bevacizumab, for which he was dependent on iron infusions and packed red blood cells transfusions. He then started pazopanib at 100 mg with dramatic improvements in epistaxis and normalization of hemoglobin and iron levels, without replenishment needs for 12 months. This is the first report on the efficacy of pazopanib with high selectivity for abrogating VEGF receptor-2 signaling in HHT, and needs to be explored further. Laryngoscope, 128:2234-2236, 2018. Topics: Anemia, Iron-Deficiency; Angiogenesis Inhibitors; Bevacizumab; Epistaxis; Erythrocyte Transfusion; Hemoglobins; Humans; Indazoles; Male; Middle Aged; Pyrimidines; Sulfonamides; Telangiectasia, Hereditary Hemorrhagic | 2018 |
Selective effects of oral antiangiogenic tyrosine kinase inhibitors on an animal model of hereditary hemorrhagic telangiectasia.
Essentials Antiangiogenic drugs are indicated as therapies for hereditary hemorrhagic telangiectasia. We interrogated the response to four antiangiogenic drugs for anemia and intestinal bleeding. Sorafenib and a pazopanib analog significantly improved while erlotinib worsened anemia. Some oral antiangiogenic drugs were effective in reducing intestinal bleeding.. Background Epistaxis and gastrointestinal (GI) tract hemorrhages are common symptoms of aged hereditary hemorrhagic telangiectasia (HHT) patients that result in anemia. Clinical as well as animal studies have suggested that vascular endothelial growth factor (VEGF) neutralizing antibodies lessen hemorrhage associated with adult-onset arteriovenous malformations (AVMs). Objectives The goal of this study is to evaluate potential therapeutic effects of oral delivery of four antiangiogenic tyrosine-kinase inhibitors (TKIs) in the development of adult-onset AVMs in a murine model of HHT. Methods An adult activin receptor-like kinase 1 (Alk1)-inducible knockout (iKO) model was utilized to evaluate the effect of oral administration of sorafenib, sunitinib, erlotinib and a pazopanib analog (GW771806) on hemoglobin level, GI hemorrhages and formation of wound-induced skin AVMs. Results and Conclusions Sorafenib and GW771806 significantly improved, yet erlotinib worsened, anemia and GI-bleeding in the Alk1-iKO model. However, none of these TKIs appeared to be effective for inhibiting the development of wound-induced skin AVMs. Taken together, these results suggest that oral delivery of antiangiogenic TKIs is selectively more effective for GI bleeding than mucocutaneous AVMs, and it may provide an experimental basis for selective therapeutic options depending on the symptoms of HHT. Topics: Activin Receptors, Type I; Activin Receptors, Type II; Administration, Oral; Administration, Topical; Anemia; Angiogenesis Inhibitors; Animals; Arteriovenous Malformations; Disease Models, Animal; Erlotinib Hydrochloride; Gastrointestinal Hemorrhage; Hemoglobins; Image Processing, Computer-Assisted; Indazoles; Mice; Mice, Knockout; Niacinamide; Phenylurea Compounds; Protein Kinase Inhibitors; Pyrimidines; Skin; Sorafenib; Sulfonamides; Sulfones; Telangiectasia, Hereditary Hemorrhagic; Tyrosine; Vascular Endothelial Growth Factor A; Wound Healing | 2017 |