肺癌からの転移性脳腫瘍におけるEGFR遺伝子変異とgefitinibの有効性

Antitumor Effects of Gefitinib for Metastatic Brain Tumors from Lung Carcinomas with EGFR Mutation

Ⅰ．はじめに

　肺癌からの脳転移の多くは，一部の腫瘍を除いて一般に化学療法が奏効しにくいため，最近まで手術摘出と放射線治療が主たる治療手段であった．最近，原発巣の非小細胞肺癌に対して上皮成長因子受容体（epidermal growth factor receptor：EGFR）遺伝子変異（以下，EGFR変異）をもつ症例に関してはEGFRチロシンキナーゼ阻害剤（tyrosine kinase inhibitor：TKI）の有効性が示唆されている^6,7,11)．今回，われわれは非小細胞肺癌の転移性脳腫瘍においてEGFR変異とEGFR-TKIの初期治療としての抗腫瘍効果について検討を行った．

　Objective: Patients with lung cancer harboring epidermal growth factor receptor (EGFR) mutation respond remarkably well to tyrosine kinase inhibitors of the EGFR (EGFR-TKI). We examined the relation of the EGFR mutation and the efficacy of EGFR-TKI for metastatic brain tumors from lung cancer.

　Materials and methods: Forty-one patients with brain metastases from lung cancer were treated in our hospital from January 2007 to October 2010. Among them, 9 patients were examined on their EGFR mutation of tumors using the PNA-LNA PCR clamp method, and were treated with gefitinib, given orally at a daily dose of 250 mg. The drug efficacy for brain tumors was evaluated with MRI and CT.

　Results: Seven patients had EGFR mutation (4 in exon 19, and 3 in exon 21). Five patients showed partial response, 3 remained stable, and one had progressive disease. All 5 patients who showed partial response had EGFR mutation. One patient who had progressive disease had no EGFR mutation. Three patients (case 1, 2 and 6) among 5 patients who showed partial response were well controlled only with gefitinib (without radiation).

　Conclusion: This study suggests that the efficacy of EGFR-TKI for metastatic brain tumors from lung cancer is related to the EGFR mutation of tumor.