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━━ Background. As the incidence of lung cancer and pulmonary non-tuberculous mycobacterial (NTM) infection is increasing, the incidence of coexistent lung cancer and pulmonary NTM infection is also increasing. Evidence shows that drug interactions can be problematic in the treatment of coexisting lung cancer and pulmonary NTM infection. Gefitinib is normally used to treat lung cancer. However, CYP3A4 inducers, such as rifampicin and rifabutin, reduce the concentration of gefitinib in the blood, whereas CYP3A4 inhibitors, such as clarithromycin, increase its concentration. Consequently, drug interaction is a major problem when gefitinib is used to treat lung cancer in patients with progressive pulmonary NTM infection. Case. A 72-year-old man was diagnosed with stage IV lung cancer. The cancer was pathologically identified as an adenocarcinoma, and a driver mutation of the epidermal growth factor receptor (L858R) was identified. The patient was treated with gefitinib, but he subsequently developed a progressive pulmonary Mycobacterium avium infection. We also identified drug interactions between gefitinib and rifampicin, rifabutin and clarithromycin. The patient’s blood gefitinib concentration was measured because combination therapy with these drugs can lead to instability in the concentration of gefitinib and tumor progression. The gefitinib concentration was reduced to 60% of the original concentration following the administration of rifabutin but increased to 130% of the original concentration after the administration of rifabutin, clarithromycin, and ethambutol. However, the patient developed hyperbilirubinemia after the combined administration of rifabutin, clarithromycin, and ethambutol, and as a consequence, the combination therapy was discontinued. Afatinib is a drug that is largely considered to be unaffected by the CYP3A4 metabolism. Thus, afatinib was administered with clarithromycin, ethambutol, and rifampicin; however, the patient experienced side effects and the therapy was discontinued. Conclusion. We herein presented a case of a patient with coexisting lung cancer and pulmonary Mycobacterium avium complex disease, who was treated with gefitinib, rifabutin, clarithromycin, and ethambutol. However, this combination therapy resulted in both drug interactions and side effects. It is therefore very important to consider drug interactions and side effects in the treatment of coexisting lung cancer and pulmonary NTM infection. (JJLC. 2016;56:355-360) KEY WORDS━━ Lung cancer, Gefitinib, Rifampicin, CYP3A4, Non-tuberculous mycobacterial infection Corresponding author: Hiroshi Ito. Received December 21, 2015; accepted June 27, 2016. 労働者健康安全機構中部労災病院 1呼吸器内科,2薬剤部;3国立 研究開発法人国立長寿医療研究センター呼吸器科;4公益財団法人 がん研究会有明病院呼吸器センター. 論文責任者:伊藤 浩. 受付日:2015 年 12 月 21 日,採択日:2016 年 6 月 27 日. (肺癌.2016;56:355-360) 2016 The Japan Lung Cancer Society Coexisting Lung Cancer and Non-tuberculous Mycobacterial Infection Treated with Gefitinib―Ito et al 356 Japanese Journal of Lung Cancer―Vol 56, No 5, Oct 20, 2016―www.haigan.gr.jp 要旨━━背景.肺癌および非結核性肺抗酸菌症(肺 NTM症)は増加傾向で,両疾患の合併例の増加も見込ま れる.両疾患の治療薬には薬物相互作用が知られている. 肺癌治療Gefitinib の血中濃度はCYP3A4 誘導剤のリ ファンピシンやリファブチン(RBT)で低下,CYP3A4 阻害薬のクラリスロマイシン(CAM)で上昇し得るため 注意を要する.症例.72 歳男性.右上葉肺腺癌 stage IV, EGFR遺伝子変異陽性の診断でGefitinib を投与中,進行 性の肺NTM症で治療を要した.薬物相互作用が懸念さ れ,Gefitinib の血中濃度を測定した.Gefitinib の血中濃 度は,RBT併用で 60%に,RBT+CAM+エタンブトー ルの 3剤併用で 130%に変動した.併用治療は肝機能障 害のため継続困難であった.CYP3A4 で代謝のない Afatinib も肺 NTM症治療薬と併用を試みたが,副作用 で継続困難であった.結論.進行肺癌の予後は改善傾向 にあり,肺NTM症合併の治療が必要な症例の増加も見 込まれるが,薬物相互作用の観点で検討が必要と考えら れる. 索引用語━━肺 癌,Gefitinib,リ フ ァ ン ピ シ ン, CYP3A4,非結核性抗酸菌症

haigan

The Treatment of Coexisting Lung Cancer and &lt;i&gt;Mycobacterium avium&lt;/i&gt; Complex Infection with Gefitinib, Rifabutin, Clarithromycin, and Ethambutol, Concomitant with the Measurement of the Blood Gefitinib Concentration: a Case Report