Elsevier

Journal of Thoracic Oncology

Volume 4, Issue 11, November 2009, Pages 1415-1419
Journal of Thoracic Oncology

Original Article
Efficacy of Erlotinib for Brain and Leptomeningeal Metastases in Patients with Lung Adenocarcinoma Who Showed Initial Good Response to Gefitinib

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Introduction

The efficacy of high-dose (1250 mg/d) gefitinib for the treatment of leptomeningeal metastasis in a patient with lung cancer harboring a mutation in the epidermal growth factor receptor (EGFR) gene was previously reported. We speculate that erlotinib, instead of high dose of gefitinib, may be also effective for the treatment of central nervous system (CNS) lesions, as trough serum concentration of erlotinib is nine times higher than that of gefitinib.

Patients and Methods

Patients with lung cancer in whom CNS lesions developed after an initial good response to gefitinib for extra CNS lesions were enrolled in the study. Tumor response, performance status, neurologic symptoms, and survival were retrospectively evaluated.

Results

All seven patients had EGFR mutations in their primary tumors except one patient. The median interval between gefitinib withdrawal and erlotinib administration was 5 days. Three patients showed partial response, three had stable disease, and one had progressive disease. Performance status and symptoms improved in five patients. The overall survival from the initiation of erlotinib treatment ranged from 15 to 530 days (median, 88 days).

Conclusions

Erlotinib was a reasonable option for the treatment of CNS diseases that appeared after a good initial response of extra CNS disease to gefitinib.

Key Words

Lung cancer
Brain metastasis
EGFR-TKI
BBB
CNS

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Disclosure: Dr. Mitsudomi was paid an honorarium as a speaker in the professional meeting from AstraZeneca, Chugai pharm, Daiichi-Sankyo, Bristol-Meyers, Astells, and Taiho. He also provided testimony at the Japanese court in relation to the efficacy and toxicity of gefitinib. The other authors declare no conflicts of interest.