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

Erlotinib for Progressive Vestibular Schwannoma in Neurofibromatosis 2 Patients

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Free PMC article

Erlotinib for Progressive Vestibular Schwannoma in Neurofibromatosis 2 Patients

Scott R Plotkin et al. Otol Neurotol. .
Free PMC article

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.

Figures

Figure 1
Figure 1
Changes in tumor volume after treatment using erlotinib 150 mg daily. “0” indicates initiation of treatment. The vertical line indicates the start of treatment (day 0). (a) Four tumors were stable during treatment, defined as change in tumor volume between 19% growth and 19% shrinkage compared to the baseline volume. (b) Six tumors progressed during treatment, defined as an increase in tumor volume of greater than or equal to 20% compared to the baseline volume. (c) Time to tumor progression in 10 evaluable patients.
Figure 1
Figure 1
Changes in tumor volume after treatment using erlotinib 150 mg daily. “0” indicates initiation of treatment. The vertical line indicates the start of treatment (day 0). (a) Four tumors were stable during treatment, defined as change in tumor volume between 19% growth and 19% shrinkage compared to the baseline volume. (b) Six tumors progressed during treatment, defined as an increase in tumor volume of greater than or equal to 20% compared to the baseline volume. (c) Time to tumor progression in 10 evaluable patients.
Figure 1
Figure 1
Changes in tumor volume after treatment using erlotinib 150 mg daily. “0” indicates initiation of treatment. The vertical line indicates the start of treatment (day 0). (a) Four tumors were stable during treatment, defined as change in tumor volume between 19% growth and 19% shrinkage compared to the baseline volume. (b) Six tumors progressed during treatment, defined as an increase in tumor volume of greater than or equal to 20% compared to the baseline volume. (c) Time to tumor progression in 10 evaluable patients.
Figure 2
Figure 2
Change in word recognition after treatment using erlotinib 150 mg daily. The vertical line indicates the start of treatment (day 0). Patients who did not undergo audiologic evaluation (n=1) and those with surgical resection of both auditory nerves (n=1) were excluded from analysis. One patient was tested only with pure tone audiometry. (a) Stable word recognition scores were documented in five patients during treatment. (b) Progressive hearing loss was documented in 3 patients, including one patient with transient hearing improvement. * indicate timepoints qualifying as a hearing response. (c) Time to progressive hearing loss in 7 evaluable patients.
Figure 2
Figure 2
Change in word recognition after treatment using erlotinib 150 mg daily. The vertical line indicates the start of treatment (day 0). Patients who did not undergo audiologic evaluation (n=1) and those with surgical resection of both auditory nerves (n=1) were excluded from analysis. One patient was tested only with pure tone audiometry. (a) Stable word recognition scores were documented in five patients during treatment. (b) Progressive hearing loss was documented in 3 patients, including one patient with transient hearing improvement. * indicate timepoints qualifying as a hearing response. (c) Time to progressive hearing loss in 7 evaluable patients.
Figure 2
Figure 2
Change in word recognition after treatment using erlotinib 150 mg daily. The vertical line indicates the start of treatment (day 0). Patients who did not undergo audiologic evaluation (n=1) and those with surgical resection of both auditory nerves (n=1) were excluded from analysis. One patient was tested only with pure tone audiometry. (a) Stable word recognition scores were documented in five patients during treatment. (b) Progressive hearing loss was documented in 3 patients, including one patient with transient hearing improvement. * indicate timepoints qualifying as a hearing response. (c) Time to progressive hearing loss in 7 evaluable patients.
Figure 3
Figure 3
Change in pure-tone thresholds after treatment using erlotinib 150 mg daily. The vertical line indicates the start of treatment (day 0). Patients who did not undergo audiologic evaluation (n=1) and those with surgical resection of both auditory nerves (n=1) were excluded from analysis. (a) Minor response (defined as increase in pure tone average of 10 dBHL from baseline in the setting of stable word recognition) was noted in two patients and stable hearing in three patients. (b) Progressive hearing decline was documented in 3 patients.
Figure 3
Figure 3
Change in pure-tone thresholds after treatment using erlotinib 150 mg daily. The vertical line indicates the start of treatment (day 0). Patients who did not undergo audiologic evaluation (n=1) and those with surgical resection of both auditory nerves (n=1) were excluded from analysis. (a) Minor response (defined as increase in pure tone average of 10 dBHL from baseline in the setting of stable word recognition) was noted in two patients and stable hearing in three patients. (b) Progressive hearing decline was documented in 3 patients.

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