Erlotinib for progressive vestibular schwannoma in neurofibromatosis 2 patients.
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).


METHODS
Retrospective case review.


METHODS
Tertiary referral center.


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


METHODS
Erlotinib 150 mg daily.


METHODS
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.


CONCLUSIONS
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.
Plotkin
Scott R
SR
Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts 02114, U.S.A. splotkin@partners.org
Halpin
Chris
C
McKenna
Michael J
MJ
Loeffler
Jay S
JS
Batchelor
Tracy T
TT
Barker
Fred G
FG
D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001301:Audiometry, Pure-Tone; D018450:Disease Progression; D000069347:Erlotinib Hydrochloride; D005260:Female; D006319:Hearing Loss, Sensorineural / Q000150:complications; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D016518:Neurofibromatosis 2 / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D009464:Neuroma, Acoustic / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D011799:Quinazolines / Q000009:adverse effects / Q000627:therapeutic use*; D013067:Speech Perception / Q000502:physiology; D016896:Treatment Outcome; D055815:Young Adult
D000970:Antineoplastic Agents; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride