The effect of bevacizumab on vestibular schwannoma tumour size and hearing in patients with neurofibromatosis type 2

Eur Arch Otorhinolaryngol. 2015 Dec;272(12):3627-33. doi: 10.1007/s00405-014-3398-3. Epub 2014 Nov 25.

Abstract

The hallmark of neurofibromatosis type 2 (NF2) is bilateral vestibular schwannomas (VS) and severe hearing loss is common in NF2 patients. Vascular endothelial growth factor (VEGF) expression level in NF2 correlates with tumour growth rate and bevacizumab, a VEGF-binding antibody, has previously been shown to induce tumour shrinkage and improve hearing. We retrospectively reviewed the effect of bevacizumab on hearing and VS tumour size in 12 consecutive NF2 patients. Bevacizumab 10 mg/kg was administered intravenously every second week for 6 months; hereafter, bevacizumab 15 mg/kg was administered every third week. Patients were evaluated with repeated audiometries, MR scans and clinical evaluations. Radiological response was defined as a 20 % or greater reduction in VS volume. A total of 398 treatments (median 36) were administered and the median duration on therapy was 22 months (range 7-34). We observed a radiological response (≥20 % tumour shrinkage) in seven out of 18 tumours (39 %) in six out of 12 patients (50 %). Sustained radiological responses were maintained in six tumours (33 %) for more than 2 months. Three patients had objectively improved hearing and five patients reported subjective benefit in neurological symptoms, including improved hearing. Toxicity was in general manageable; however, one patient died from cerebral haemorrhage which was possibly related to therapy. In conclusion, bevacizumab improved hearing and reduced the size of VS in some patients with progressive NF2 which corroborates previous findings; however, the risk of severe side effects should be carefully considered and discussed with the patients prior to treatment.

Keywords: Avastin; Bevacizumab; NF2; Vestibular schwannoma.

MeSH terms

  • Adult
  • Aged
  • Angiogenesis Inhibitors / administration & dosage
  • Angiogenesis Inhibitors / adverse effects
  • Audiometry / methods
  • Bevacizumab* / administration & dosage
  • Bevacizumab* / adverse effects
  • Cerebral Hemorrhage / etiology*
  • Female
  • Hearing / drug effects*
  • Humans
  • Magnetic Resonance Imaging / methods
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Neurofibromatosis 2* / drug therapy
  • Neurofibromatosis 2* / metabolism
  • Neurofibromatosis 2* / pathology
  • Neuroma, Acoustic* / drug therapy
  • Neuroma, Acoustic* / metabolism
  • Neuroma, Acoustic* / pathology
  • Retrospective Studies
  • Treatment Outcome
  • Tumor Burden / drug effects*
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Angiogenesis Inhibitors
  • Vascular Endothelial Growth Factor A
  • Bevacizumab