Skip to main content

Advertisement

Log in

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

  • Rhinology
  • Published:
European Archives of Oto-Rhino-Laryngology Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Geisthoff UW, Schneider G, Fischinger J, Plinkert PK (2002) Hereditäre hämorrhagische Teleangiektasie (Morbus Osler). HNO 50:114–128

    Article  PubMed  CAS  Google Scholar 

  2. 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 93:320–327

    Article  PubMed  CAS  Google Scholar 

  3. Govani FS, Shovlin CL (2009) Hereditary haemorrhagic telangiectasia: a clinical and scientific review. Eur J Hum Genet 17:860–871

    Article  PubMed  CAS  Google Scholar 

  4. Shovlin CL, Guttmacher AE, Buscarini E et al (2000) Diagnostic criteria for hereditary hemorrhagic telangiectasia (Rendu–Osler–Weber syndrome). Am J Med Genet 91:66–67

    Article  PubMed  CAS  Google Scholar 

  5. 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 23:52–58

    Article  PubMed  Google Scholar 

  6. 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 263:53–61

    Article  PubMed  Google Scholar 

  7. 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 119:284–288

    Article  PubMed  CAS  Google Scholar 

  8. 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

    Google Scholar 

  9. Lund VJ, Howard DJ (1996) Closure of the nasal cavities in the treatment of refractory hereditary haemorrhagic teleangiectasia. J Laryngol Otol 111:30–33

    Google Scholar 

  10. 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 22:182–187

    Article  PubMed  Google Scholar 

  11. 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 262:830–833

    Article  PubMed  Google Scholar 

  12. 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 22:575–580

    PubMed  CAS  Google Scholar 

  13. 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 90:818–828

    PubMed  CAS  Google Scholar 

  14. 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 110:29–32

    Article  PubMed  CAS  Google Scholar 

  15. Mukherji SK (2010) Bevacizumab (Avastin). AJNR 31:235–236

    Article  PubMed  CAS  Google Scholar 

  16. 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 101:238–243

    Article  PubMed  CAS  Google Scholar 

  17. 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) 23:2223–2227

    Article  CAS  Google Scholar 

  18. Hoag JB, Terry P, Mitchell S, Reh D, Merlo CA (2010) An epistaxis severity score for hereditary hemorrhagic telangiectasia. Laryngoscope 120:838–843

    Article  PubMed  Google Scholar 

  19. Kuehnel TS, Wagner BH, Schurr CP, Strutz J (2005) Clinical strategy in hereditary hemorrhagic telangiectasia. Am J Rhinol 19:508–513

    Google Scholar 

  20. Dvorak HF, Brown LF, Detmar M, Dvorak AM (1995) Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability, and angiogenesis. Am J Pathol 146:1029–1039

    PubMed  CAS  Google Scholar 

  21. 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)

    Google Scholar 

  22. Simonds J, Miller F, Mandel J, Davidson TM (2009) The effect of bevacizumab (Avastin) treatment on epistaxis in hereditary hemorrhagic telangiectasia. Laryngoscope 119:988–992

    Article  PubMed  CAS  Google Scholar 

  23. Randall LM, Monk BJ (2010) Bevacizumab toxicities and their management in ovarian cancer. Gynecol Oncol 117:497–504

    Article  PubMed  CAS  Google Scholar 

  24. Karnezis TT, Davidson TM (2011) Efficacy of intranasal Bevacizumab (Avastin) treatment in patients with hereditary hemorrhagic telangiectasia-associated epistaxis. Laryngoscope 121:636–638

    Article  PubMed  CAS  Google Scholar 

  25. Retornaz F, Rinaldi Y, Duvoux C (2009) More on bevacizumab in hereditary hemorrhagic telangiectasia. N Engl J Med 361:931–932

    Article  PubMed  CAS  Google Scholar 

  26. Oosting S, Nagengast W, de Vries E (2009) More on bevacizumab in hereditary hemorrhagic telangiectasia. N Engl J Med 361:931–932

    Article  PubMed  CAS  Google Scholar 

  27. Bose P, Holter JL, Selby GB (2009) Bevacizumab in hereditary hemorrhagic telangiectasia. N Engl J Med 360:2143–2144

    Article  PubMed  CAS  Google Scholar 

  28. 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 85:631–632

    Article  PubMed  Google Scholar 

  29. Bose P, Holter JL, Selby GB (2009) More on bevacizumab in hereditary hemorrhagic telangiectasia. N Engl J Med 361:931–932

    Article  CAS  Google Scholar 

  30. Davidson TM, Olitsky SE, Wei JL (2010) Hereditary hemorrhagic telangiectasia/avastin. Laryngoscope 120:432–435

    PubMed  Google Scholar 

Download references

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to C. Rohrmeier.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rohrmeier, C., Sachs, H.G. & Kuehnel, T.S. A retrospective analysis of low dose, intranasal injected bevacizumab (Avastin) in hereditary haemorrhagic telangiectasia. Eur Arch Otorhinolaryngol 269, 531–536 (2012). https://doi.org/10.1007/s00405-011-1721-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00405-011-1721-9

Keywords

Navigation