Erlotinib for progressive vestibular schwannoma in neurofibromatosis 2 patients

Otol Neurotol. 2010 Sep;31(7):1135-43. doi: 10.1097/MAO.0b013e3181eb328a.

Abstract

Objective: In vitro treatment of Nf2-deficient cells with epidermal growth factor receptor (EGFR) inhibitors can reduce cellular proliferation. We sought to determine the activity of erlotinib for progressive vestibular schwannoma (VS) associated with neurofibromatosis 2 (NF2).

Study design: Retrospective case review.

Setting: Tertiary referral center.

Patients: Eleven NF2 patients with progressive VS who were poor candidates for standard therapy.

Intervention: Erlotinib 150 mg daily.

Main outcome measures: A radiographic response was defined as >or= 20% decrease in tumor volume compared with baseline. A hearing response was defined as a statistically significant increase in word recognition score (WRS) compared with baseline; a minor hearing response was defined as a 10 dB improvement in pure-tone average with stable WRS.

Results: : Before treatment, the median and mean annual volumetric growth rate for 11 index VS were 26% and 46%, respectively. Among 10 evaluable patients, the median time-to-tumor progression was 9.2 months. Three patients with stable disease experienced maximum tumor shrinkage of 4%, 13%, and 14%. Nine patients underwent audiologic evaluations. One experienced a transient hearing response, 2 experienced minor hearing responses, 3 remained stable, and 2 developed progressive hearing loss. The median time-to-progressive hearing loss was 9.2 months and to either tumor growth or progressive hearing loss was 7.1 months. Adverse treatment effects included mild-to-moderate rash, diarrhea, and hair thinning, with 2 episodes of grade 3 toxicity.

Conclusion: Erlotinib treatment was not associated with radiographic or hearing responses in NF2 patients with progressive VS. Because a subset of patients experienced prolonged stable disease, time-to-progression may be more appropriate than radiographic or hearing response for anti-EGFR agents in NF2-associated VS.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Audiometry, Pure-Tone
  • Disease Progression
  • Erlotinib Hydrochloride
  • Female
  • Hearing Loss, Sensorineural / complications
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Neurofibromatosis 2 / complications
  • Neurofibromatosis 2 / drug therapy*
  • Neurofibromatosis 2 / pathology
  • Neuroma, Acoustic / drug therapy*
  • Neuroma, Acoustic / etiology
  • Neuroma, Acoustic / pathology
  • Quinazolines / adverse effects
  • Quinazolines / therapeutic use*
  • Speech Perception / physiology
  • Treatment Outcome
  • Young Adult

Substances

  • Antineoplastic Agents
  • Quinazolines
  • Erlotinib Hydrochloride