European Journal of Clinical Pharmacology

, Volume 68, Issue 12, pp 1685–1686

Bevacizumab treatment in hereditary hemorrhagic teleangiectasia


    • PneumologyUniversity Magdeburg
  • Michael Ibe
    • Clinic for Internal Medicine IISüdharzklinikum Nordhausen
  • Jens Schreiber
    • PneumologyUniversity Magdeburg
Letter to the Editors

DOI: 10.1007/s00228-012-1308-4

Cite this article as:
Föllner, S., Ibe, M. & Schreiber, J. Eur J Clin Pharmacol (2012) 68: 1685. doi:10.1007/s00228-012-1308-4

To the Editor,

Taugourdeau-Raymond and co-workers reported a high frequency of severe bevacizumab-induced adverse effects in the January 2012 issue of this journal [1]. Although only patients with malignant disorders were included, these data are of outstanding importance. Nowadays bevacizumab is increasingly used for off-label treatment, e.g., in macular degeneration and hereditary hemorrhagic teleangiectasia (HHT) (Morbus Osler-Rendu-Weber syndrome). Assessment of the risk-benefit ratio demands awareness of treatment failures in this setting.

There are several reports on positive effects of treating HHT with bevacizumab, an antibody against the vascular endothelial growth factor (VEGF) [29]. This is the first report on failure of this therapy. HHT is characterized by arteriovenous malformations that may occur in various organs and lead to epistaxis and gastrointestinal and pulmonary bleeding among other manifestations. There is no curative therapy so far.

We report on two patients with HHT, who were treated with bevacizumab because of life-threatening bleeding. An 82-year-old man with predominantly gastrointestinal lesions needed an increasing number of red blood cell transfusions. After giving informed consent, he received three cycles of bevacizumab 5 mg/kg b.w. biweekly. The therapy was well tolerated and no erythrocyte transfusion was necessary the following 6 weeks, however this effect was temporary (Fig. 1). In a 55-year-old female patient, episodes of severe epistaxis led to transplantation of nasal mucosa. Furthermore an increasing number of gastric lesions were treated with laser applications. The course was complicated by the development of transfusion-associated antibodies with consecutive transfusion reactions. She gave informed consent, and bevacizumab treatment was initiated (5 mg/kg b.w., biweekly, three cycles). In contrast to our first case and several cases published in the literature, we did not observe any effect on the number of red blood cell transfusions required (Fig. 1).
Fig. 1

Time course of minimum hemoglobin concentration and transfusion needs in two patients with hereditary hemorrhagic telangiectasia treated with bevacizumab (BEV). Triangles Number of red blood cell transfusions, diamonds hemoglobin levels

These two cases demonstrate that efficacy of bevacizumab-treatment in HHT is not definitive and not predictable. One possible explanation might be that VEGF is expressed differently in different genetic variants of the disease [10]. We presume that a variation in the structure of VEGF in HHT can cause resistance against bevacizumab.

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© Springer-Verlag 2012