Watanabe Kousuke, Kage Hidenori, Nagoshi Saki, Toyama Kazuhiro, Ohno Yoshiyuki, Shinozaki-Ushiku Aya, Nakazaki Kumi, Suzuki Hiroshi, Kurokawa Mineo, Nagase Takahide
Department of Respiratory Medicine, The University of Tokyo, Tokyo, Japan.
Department of Hematology and Oncology, The University of Tokyo, Tokyo, Japan.
Case Rep Oncol Med. 2020 Mar 19;2020:4201727. doi: 10.1155/2020/4201727. eCollection 2020.
Tyrosine kinase inhibitor (TKI) combination is expected to increase in the era of precision medicine. TKI combination may be required to treat double primary cancers, each having a targetable gene, or to treat a single malignancy with multiple targetable genes. Here, we demonstrate the first report of dual EGFR and ABL TKI treatment in a patient with concomitant EGFR-mutated lung adenocarcinoma and BCR-ABL1-positive chronic myeloid leukemia (CML). A 60-year-old man with an 8-year history of CML was diagnosed as advanced EGFR-mutated lung adenocarcinoma. Complete molecular response of CML had been achieved by imatinib, and ABL-TKI had been switched to nilotinib four years previously due to muscle cramps. We discontinued nilotinib and started afatinib. Although partial response of lung adenocarcinoma was achieved, cytogenetic relapse of CML was observed following nilotinib discontinuation. We applied the previously described framework of cytochrome P450 3A4-mediated oral drug-drug interactions and selected gefitinib and nilotinib to treat both malignancies. We effectively and safely administered this combination for seven months. The present report is the first to demonstrate the safety and efficacy of dual EGFR and ABL TKI treatment in a patient with concomitant EGFR-mutated lung adenocarcinoma and CML.
在精准医学时代，酪氨酸激酶抑制剂（TKI）联合治疗有望增加。对于患有两种均具有可靶向基因的原发性癌症，或对于具有多个可靶向基因的单一恶性肿瘤，可能需要进行TKI联合治疗。在此，我们首次报告了一名同时患有EGFR突变型肺腺癌和BCR-ABL1阳性慢性髓性白血病（CML）的患者接受EGFR和ABL双靶点TKI治疗的情况。一名有8年CML病史的60岁男性被诊断为晚期EGFR突变型肺腺癌。伊马替尼已使CML达到完全分子反应，且由于肌肉痉挛，4年前ABL-TKI已换用尼罗替尼。我们停用尼罗替尼并开始使用阿法替尼。虽然肺腺癌实现了部分缓解，但停用尼罗替尼后观察到CML细胞遗传学复发。我们应用先前描述的细胞色素P450 3A4介导的口服药物-药物相互作用框架，选择吉非替尼和尼罗替尼来治疗这两种恶性肿瘤。我们有效且安全地给予这种联合治疗7个月。本报告首次证明了EGFR和ABL双靶点TKI治疗同时患有EGFR突变型肺腺癌和CML患者的安全性和有效性。
