Skip to main content
Top
Published in: European Archives of Oto-Rhino-Laryngology 2/2012

01-02-2012 | Rhinology

A retrospective analysis of low dose, intranasal injected bevacizumab (Avastin) in hereditary haemorrhagic telangiectasia

Authors: C. Rohrmeier, H. G. Sachs, T. S. Kuehnel

Published in: European Archives of Oto-Rhino-Laryngology | Issue 2/2012

Login to get access

Abstract

The constantly recurring epistaxis means a great reduction of quality of life for patients with hereditary haemorrhagic telangiectasia (HHT). As yet, an ideal treatment has not been found. Vascular endothelial growth factor (VEGF) has been described as a possible new therapy. In particular, the success of submucosal doses <100 mg has not been analysed before. We injected bevacizumab (Avastin) submucosally in addition to Nd:YAG laser therapy. Doses <7.5 mg were used. To investigate the effect of these additional injections in comparison to laser therapy alone, a retrospective analysis was done. For this purpose a standardized patient questionnaire was completed, which included recording the patients’ Epistaxis Severity Score (ESS) before and after the antibody treatment. Besides, patient files were analysed to collect objective data like haemoglobin levels and the number of blood transfusions needed. Data for eleven patients could be analysed. A significant improvement in the ESS resulting from additional bevacizumab therapy was observed (p < 0.01). In particular, the frequency of epistaxis (p = 0.011), duration of epistaxis (p < 0.01), severity of epistaxis (p < 0.01) and the need for acute medical treatment (p = 0.014) decreased significantly. The haemoglobin levels increased significantly (p = 0.011) and the number of blood transfusions declined. There were no side effects caused by the antibody treatment. Additional injections of a low dose of bevacizumab seem to be superior to Nd:YAG laser therapy alone. These results justify further studies.
Literature
1.
go back to reference Geisthoff UW, Schneider G, Fischinger J, Plinkert PK (2002) Hereditäre hämorrhagische Teleangiektasie (Morbus Osler). HNO 50:114–128PubMedCrossRef Geisthoff UW, Schneider G, Fischinger J, Plinkert PK (2002) Hereditäre hämorrhagische Teleangiektasie (Morbus Osler). HNO 50:114–128PubMedCrossRef
2.
go back to reference McDonald JE, Miller FJ, Hallam SE, Nelson L, Marchuk DA, Ward KJ (2000) Clinical manifestations in a large hereditary hemorrhagic telangiectasia (HHT) type 2 kindred. Am J Med Genet 93:320–327PubMedCrossRef McDonald JE, Miller FJ, Hallam SE, Nelson L, Marchuk DA, Ward KJ (2000) Clinical manifestations in a large hereditary hemorrhagic telangiectasia (HHT) type 2 kindred. Am J Med Genet 93:320–327PubMedCrossRef
3.
go back to reference Govani FS, Shovlin CL (2009) Hereditary haemorrhagic telangiectasia: a clinical and scientific review. Eur J Hum Genet 17:860–871PubMedCrossRef Govani FS, Shovlin CL (2009) Hereditary haemorrhagic telangiectasia: a clinical and scientific review. Eur J Hum Genet 17:860–871PubMedCrossRef
4.
go back to reference Shovlin CL, Guttmacher AE, Buscarini E et al (2000) Diagnostic criteria for hereditary hemorrhagic telangiectasia (Rendu–Osler–Weber syndrome). Am J Med Genet 91:66–67PubMedCrossRef Shovlin CL, Guttmacher AE, Buscarini E et al (2000) Diagnostic criteria for hereditary hemorrhagic telangiectasia (Rendu–Osler–Weber syndrome). Am J Med Genet 91:66–67PubMedCrossRef
5.
go back to reference Pagella F, Colombo A, Matti E et al (2009) Correlation of severity of epistaxis with nasal telangiectasias in hereditary hemorrhagic telangiectasia (HHT) patients. Am J Rhinol Allergy 23:52–58PubMedCrossRef Pagella F, Colombo A, Matti E et al (2009) Correlation of severity of epistaxis with nasal telangiectasias in hereditary hemorrhagic telangiectasia (HHT) patients. Am J Rhinol Allergy 23:52–58PubMedCrossRef
6.
go back to reference Folz BJ, Zoll B, Alfke H, Toussaint A, Maier RF, Werner JA (2006) Manifestations of hereditary hemorrhagic telangiectasia in children and adolescents. Eur Arch Otorhinolaryngol 263:53–61PubMedCrossRef Folz BJ, Zoll B, Alfke H, Toussaint A, Maier RF, Werner JA (2006) Manifestations of hereditary hemorrhagic telangiectasia in children and adolescents. Eur Arch Otorhinolaryngol 263:53–61PubMedCrossRef
7.
go back to reference Yaniv E, Preis M, Hadar T, Shvero J, Haddad M (2009) Antiestrogen therapy for hereditary hemorrhagic telangiectasia: a double-blind placebo-controlled clinical trial. Laryngoscope 119:284–288PubMedCrossRef Yaniv E, Preis M, Hadar T, Shvero J, Haddad M (2009) Antiestrogen therapy for hereditary hemorrhagic telangiectasia: a double-blind placebo-controlled clinical trial. Laryngoscope 119:284–288PubMedCrossRef
8.
go back to reference Fernandez L, Garrido-Martin EM, Sanz-Rodriguez F et al (2007) Therapeutic action of tranexamic acid in hereditary haemorrhagic telangiectasia (HHT): regulation of ALK-1/endoglin pathway in endothelial cells. Thromb Haemost 97:254–262 Fernandez L, Garrido-Martin EM, Sanz-Rodriguez F et al (2007) Therapeutic action of tranexamic acid in hereditary haemorrhagic telangiectasia (HHT): regulation of ALK-1/endoglin pathway in endothelial cells. Thromb Haemost 97:254–262
9.
go back to reference Lund VJ, Howard DJ (1996) Closure of the nasal cavities in the treatment of refractory hereditary haemorrhagic teleangiectasia. J Laryngol Otol 111:30–33 Lund VJ, Howard DJ (1996) Closure of the nasal cavities in the treatment of refractory hereditary haemorrhagic teleangiectasia. J Laryngol Otol 111:30–33
10.
go back to reference Harvey RJ, Kanagalingam J, Lund VJ (2008) The impact of septodermoplasty and potassium-titanyl-phosphate (KTP) laser therapy in the treatment of hereditary hemorrhagic telangiectasia-related epistaxis. Am J Rhinol 22:182–187PubMedCrossRef Harvey RJ, Kanagalingam J, Lund VJ (2008) The impact of septodermoplasty and potassium-titanyl-phosphate (KTP) laser therapy in the treatment of hereditary hemorrhagic telangiectasia-related epistaxis. Am J Rhinol 22:182–187PubMedCrossRef
11.
go back to reference Karapantzos I, Tsimpiris N, Goulis DG, Van Hoecke H, Van Cauwenberge P, Danielides V (2005) Management of epistaxis in hereditary hemorrhagic telangiectasia by Nd:YAG laser and quality of life assessment using the HR-QoL questionnaire. Eur Arch Otorhinolaryngol 262:830–833PubMedCrossRef Karapantzos I, Tsimpiris N, Goulis DG, Van Hoecke H, Van Cauwenberge P, Danielides V (2005) Management of epistaxis in hereditary hemorrhagic telangiectasia by Nd:YAG laser and quality of life assessment using the HR-QoL questionnaire. Eur Arch Otorhinolaryngol 262:830–833PubMedCrossRef
12.
go back to reference Sadick H, Hage J, Goessler U et al (2008) Does the genotype of HHT patients with mutations of the ENG and ACVRL1 gene correlate to different expression levels of the angiogenic factor VEGF? Int J Mol Med 22:575–580PubMed Sadick H, Hage J, Goessler U et al (2008) Does the genotype of HHT patients with mutations of the ENG and ACVRL1 gene correlate to different expression levels of the angiogenic factor VEGF? Int J Mol Med 22:575–580PubMed
13.
go back to reference Sadick H, Riedel F, Naim R et al (2005) Patients with hereditary hemorrhagic telangiectasia have increased plasma levels of vascular endothelial growth factor and transforming growth factor-beta1 as well as high ALK1 tissue expression. Haematologica 90:818–828PubMed Sadick H, Riedel F, Naim R et al (2005) Patients with hereditary hemorrhagic telangiectasia have increased plasma levels of vascular endothelial growth factor and transforming growth factor-beta1 as well as high ALK1 tissue expression. Haematologica 90:818–828PubMed
14.
go back to reference Cirulli A, Liso A, D’Ovidio F et al (2003) Vascular endothelial growth factor serum levels are elevated in patients with hereditary hemorrhagic telangiectasia. Acta Haematol 110:29–32PubMedCrossRef Cirulli A, Liso A, D’Ovidio F et al (2003) Vascular endothelial growth factor serum levels are elevated in patients with hereditary hemorrhagic telangiectasia. Acta Haematol 110:29–32PubMedCrossRef
16.
go back to reference Thompson Coon JS, Liu Z, Hoyle M et al (2009) Sunitinib and bevacizumab for first-line treatment of metastatic renal cell carcinoma: a systematic review and indirect comparison of clinical effectiveness. Br J Cancer 101:238–243PubMedCrossRef Thompson Coon JS, Liu Z, Hoyle M et al (2009) Sunitinib and bevacizumab for first-line treatment of metastatic renal cell carcinoma: a systematic review and indirect comparison of clinical effectiveness. Br J Cancer 101:238–243PubMedCrossRef
17.
go back to reference Sacu S, Michels S, Prager F et al (2009) Randomised clinical trial of intravitreal Avastin vs photodynamic therapy and intravitreal triamcinolone: long-term results. Eye (Lond) 23:2223–2227CrossRef Sacu S, Michels S, Prager F et al (2009) Randomised clinical trial of intravitreal Avastin vs photodynamic therapy and intravitreal triamcinolone: long-term results. Eye (Lond) 23:2223–2227CrossRef
18.
go back to reference Hoag JB, Terry P, Mitchell S, Reh D, Merlo CA (2010) An epistaxis severity score for hereditary hemorrhagic telangiectasia. Laryngoscope 120:838–843PubMedCrossRef Hoag JB, Terry P, Mitchell S, Reh D, Merlo CA (2010) An epistaxis severity score for hereditary hemorrhagic telangiectasia. Laryngoscope 120:838–843PubMedCrossRef
19.
go back to reference Kuehnel TS, Wagner BH, Schurr CP, Strutz J (2005) Clinical strategy in hereditary hemorrhagic telangiectasia. Am J Rhinol 19:508–513 Kuehnel TS, Wagner BH, Schurr CP, Strutz J (2005) Clinical strategy in hereditary hemorrhagic telangiectasia. Am J Rhinol 19:508–513
20.
go back to reference Dvorak HF, Brown LF, Detmar M, Dvorak AM (1995) Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability, and angiogenesis. Am J Pathol 146:1029–1039PubMed Dvorak HF, Brown LF, Detmar M, Dvorak AM (1995) Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability, and angiogenesis. Am J Pathol 146:1029–1039PubMed
21.
go back to reference Folz B, Wollstein AC, Lippert BM, Werner JA (2005) Morphology and distribution of nasal telangiectasia in hht-patients with epistaxis. Am J Rhinol 19:70–75 (6) Folz B, Wollstein AC, Lippert BM, Werner JA (2005) Morphology and distribution of nasal telangiectasia in hht-patients with epistaxis. Am J Rhinol 19:70–75 (6)
22.
go back to reference Simonds J, Miller F, Mandel J, Davidson TM (2009) The effect of bevacizumab (Avastin) treatment on epistaxis in hereditary hemorrhagic telangiectasia. Laryngoscope 119:988–992PubMedCrossRef Simonds J, Miller F, Mandel J, Davidson TM (2009) The effect of bevacizumab (Avastin) treatment on epistaxis in hereditary hemorrhagic telangiectasia. Laryngoscope 119:988–992PubMedCrossRef
23.
go back to reference Randall LM, Monk BJ (2010) Bevacizumab toxicities and their management in ovarian cancer. Gynecol Oncol 117:497–504PubMedCrossRef Randall LM, Monk BJ (2010) Bevacizumab toxicities and their management in ovarian cancer. Gynecol Oncol 117:497–504PubMedCrossRef
24.
go back to reference Karnezis TT, Davidson TM (2011) Efficacy of intranasal Bevacizumab (Avastin) treatment in patients with hereditary hemorrhagic telangiectasia-associated epistaxis. Laryngoscope 121:636–638PubMedCrossRef Karnezis TT, Davidson TM (2011) Efficacy of intranasal Bevacizumab (Avastin) treatment in patients with hereditary hemorrhagic telangiectasia-associated epistaxis. Laryngoscope 121:636–638PubMedCrossRef
25.
go back to reference Retornaz F, Rinaldi Y, Duvoux C (2009) More on bevacizumab in hereditary hemorrhagic telangiectasia. N Engl J Med 361:931–932PubMedCrossRef Retornaz F, Rinaldi Y, Duvoux C (2009) More on bevacizumab in hereditary hemorrhagic telangiectasia. N Engl J Med 361:931–932PubMedCrossRef
26.
go back to reference Oosting S, Nagengast W, de Vries E (2009) More on bevacizumab in hereditary hemorrhagic telangiectasia. N Engl J Med 361:931–932PubMedCrossRef Oosting S, Nagengast W, de Vries E (2009) More on bevacizumab in hereditary hemorrhagic telangiectasia. N Engl J Med 361:931–932PubMedCrossRef
27.
go back to reference Bose P, Holter JL, Selby GB (2009) Bevacizumab in hereditary hemorrhagic telangiectasia. N Engl J Med 360:2143–2144PubMedCrossRef Bose P, Holter JL, Selby GB (2009) Bevacizumab in hereditary hemorrhagic telangiectasia. N Engl J Med 360:2143–2144PubMedCrossRef
28.
go back to reference Flieger D, Hainke S, Fischbach W (2006) Dramatic improvement in hereditary hemorrhagic telangiectasia after treatment with the vascular endothelial growth factor (VEGF) antagonist bevacizumab. Ann Hematol 85:631–632PubMedCrossRef Flieger D, Hainke S, Fischbach W (2006) Dramatic improvement in hereditary hemorrhagic telangiectasia after treatment with the vascular endothelial growth factor (VEGF) antagonist bevacizumab. Ann Hematol 85:631–632PubMedCrossRef
29.
go back to reference Bose P, Holter JL, Selby GB (2009) More on bevacizumab in hereditary hemorrhagic telangiectasia. N Engl J Med 361:931–932CrossRef Bose P, Holter JL, Selby GB (2009) More on bevacizumab in hereditary hemorrhagic telangiectasia. N Engl J Med 361:931–932CrossRef
30.
go back to reference Davidson TM, Olitsky SE, Wei JL (2010) Hereditary hemorrhagic telangiectasia/avastin. Laryngoscope 120:432–435PubMed Davidson TM, Olitsky SE, Wei JL (2010) Hereditary hemorrhagic telangiectasia/avastin. Laryngoscope 120:432–435PubMed
Metadata
Title
A retrospective analysis of low dose, intranasal injected bevacizumab (Avastin) in hereditary haemorrhagic telangiectasia
Authors
C. Rohrmeier
H. G. Sachs
T. S. Kuehnel
Publication date
01-02-2012
Publisher
Springer-Verlag
Published in
European Archives of Oto-Rhino-Laryngology / Issue 2/2012
Print ISSN: 0937-4477
Electronic ISSN: 1434-4726
DOI
https://doi.org/10.1007/s00405-011-1721-9

Other articles of this Issue 2/2012

European Archives of Oto-Rhino-Laryngology 2/2012 Go to the issue