Neurological Surgery 脳神経外科46巻3号

2018年03月発行

症例

Afatinibによる肺腺癌の治療中に非典型的なMRI所見を呈した脳転移の1例

著者： 宮本淳一¹ 中川享¹ 平山博²

所属機関： ¹社会福祉法人恩賜財団大阪府済生会吹田病院脳神経外科 ²社会福祉法人恩賜財団大阪府済生会吹田病院救急診療科

ページ範囲：P.213 - P.217

Ⅰ．はじめに
　肺腺癌は，遺伝子発現様式に応じてepidermal growth factor receptor-tyrosine kinase inhibitor（EGFR-TKI）やanaplastic lymphoma kinase（ALK）inhibitorで治療されるようになり，従来の治療よりもprogression free survival（PFS）が延長した^9,11)．EGFR-TKIの中でafatinibは脳転移に対して有効とされる^3,8)．今回われわれは，afatinibで治療中に，原発巣がpartial remission（PR）であるにもかかわらず脳転移巣が悪化し，非典型的なMRI所見を呈して診断に苦慮した肺腺癌脳転移の1例を経験した．Afatinibでの治療中の脳転移評価における留意点について文献的に考察し報告する．

参考文献

1) Costa DB, Shaw AT, Ou SH, Solomon BJ, Riely GJ, Ahn MJ, Zhou C, Shreeve SM, Selaru P, Polli A, Schnell P, Wilner KD, Wiltshire R, Camidge DR, Crinò L：Clinical experience with crizonitib in patients with advanced ALK-rearranged non-small-cell lung cancer and brain metastases. J Clin Oncol 33：1881-1888, 2015

2) Hayashi H, Okamoto I, Tanizaki J, Tanaka K, Okuda T, Kato A, Nishimura Y, Nakagawa K：Cystic brain metastasis in non-small-cell lung cancer with ALK rearrangement. J Clin Oncol 32：e122-124, 2014

3) Hoffknecht P, Tufman A, Wehler T, Pelzer T, Wiewrodt R, Schütz M, Serke M, Stöhlmacher-Williams J, Märten A, Maria Huber R, Dickgreber NJ；Afatinib Compassionate Use Consortium（ACUC）：Efficacy of the irreversible ErbB family blocker afatinib in epidermal growth factor receptor（EGFR）tyrosine kinase inhibitor（TKI）-pretreated non-small-cell lung cancer patients with brain metastases or leptomeningeal disease. J Thorac Oncol 10：156-163, 2015

4) Kim JE, Lee DH, Choi Y, Yoon DH, Kim SW, Suh C, Lee JS：Epidermal growth factor receptor tyrosine kinase inhibitors as a first-line therapy for never-smokers with adenocarcinoma of the lung having asymptomatic synchronous brain metastasis. Lung Cancer 65：351-354, 2009

5) 厚生労働省（編）：重篤副作用疾患別対応マニュアル　白質脳症．2006, pp.8-16

6) Lee YJ, Choi HJ, Kim SK, Chang J, Moon JW, Park IK, Kim JH, Cho BC：Frequent central nervous system failure after clinical benefit with epidermal growth factor receptor tyrosine kinase inhibitors in Korean patients with nonsmall-cell lung cancer. Cancer 116：1336-1343, 2010

7) Park K, Tan EH, O'Byrne K, Zhang L, Boyer M, Mok T, Hirsh V, Yang JC, Lee KH, Lu S, Shi Y, Kim SW, Laskin J, Kim DW, Arvis CD, ölbeck K, Laurie SA, Tsai CM, Shahidi M, Kim M, Massey D, Zazulina V, Paz-Ares L：Afatinib versus gefitinib as first-line treatment of patients with EGFR mutation-positive non-small-cell lung cancer（LUX-Lung 7）：a phase 2B, open-label, randomized controlled trial. Lancet Oncol 17：577-589, 2016

8) Saraceni C, Li PM, Gainor JF, Stopyra GA, Friedman EL：Cystic brain metastases in NSCLC harboring the EML4-ALK translocation after treatment with crizonitib. J Thorac Oncol 10：1116-1117, 2015

9) Sequist LV, Yang JC, Yamamoto N, O'Byrne K, Hirsh V, Mok T, Geater SL, Orlov S, Tsai CM, Boyer M, Su WC, Bennouna J, Kato T, Gorbunova V, Lee KH, Shah R, Massey D, Zazulina V, Shahidi M, Schuler M：Phase Ⅲ study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin Oncol 31：3327-3334, 2013

10) Taillibert S, Laigle-Donadey F, Chodkiewicz C, Sanson M, Hoang-Xuan K, Delattre JY：Leptomeningeal metastases from solid malignancy：a review. J Neurooncol 75：85-99, 2005

11) Wu YL, Zhou C, Hu CP, Feng J, Lu S, Huang Y, Li W, Hou M, Shi JH, Lee KY, Xu CR, Massey D, Kim M, Shi Y, Geater SL：Afatinib versus cisplatin plus gemcitabine for first-line treatment of Asian patients with advanced non-small-cell lung cancer harbouring EGFR mutations（LUX Lung 6）：an open-label, randomised phase 3 trial. Lancet Oncol 15：213-222, 2014