Inayat Faisal, Saif Muhammad Wasif
Department of Medicine, New York-Presbyterian Hospital, Weill Cornell Medical College, New York, NY, U.S.A.
Department of Hematology/Oncology, Tufts Medical Center, Tufts University School of Medicine, Boston, MA, U.S.A.
Anticancer Res. 2016 Nov;36(11):6201-6204. doi: 10.21873/anticanres.11214.
Molecularly targeted therapy has revolutionized the treatment of advanced gastrointestinal stromal tumors (GISTs). Specifically, the consistent dependence of GISTs on proto-oncogene c-KIT signaling led to the development and successful implementation of imatinib, a small-molecule c-KIT inhibitor. Imatinib induces, rapid and sustained clinical benefit by blocking the signaling via c-KIT. The most frequently reported adverse reactions (>30%) include edema, nausea, vomiting, muscle cramps, musculoskeletal pain, diarrhea, rash, fatigue and abdominal pain.
Herein, we report a case series of cutaneous squamous cell carcinoma (SCC) occurring secondary to imatinib in two patients treated for GISTs. Both patients were successfully managed with surgical resection of SCC and the discontinuation of the drug. Furthermore, we undertook a comprehensive literature review on this association. Few cases of cutaneous SCC secondary to imatinib therapy were reported in patients with chronic myeloid leukemia. However, there was no clinical evidence on causation of imatinib-associated SCC in patients with GIST.
To our knowledge, the present report is the first to describe imatinib-related SCC in patients undergoing treatment for GISTs. This implicates that safety and long-term tolerability of imatinib in patients with GISTs warrant rigorous testing and close monitoring.
分子靶向治疗彻底改变了晚期胃肠道间质瘤(GIST)的治疗方式。具体而言,GIST对原癌基因c-KIT信号通路的持续依赖促使了小分子c-KIT抑制剂伊马替尼的研发及成功应用。伊马替尼通过阻断c-KIT信号通路诱导快速且持续的临床获益。最常报道的不良反应(>30%)包括水肿、恶心、呕吐、肌肉痉挛、肌肉骨骼疼痛、腹泻、皮疹、疲劳和腹痛。
在此,我们报告了2例接受GIST治疗的患者继发于伊马替尼的皮肤鳞状细胞癌(SCC)病例系列。2例患者均通过手术切除SCC及停用药物成功治愈。此外,我们对这种关联进行了全面的文献综述。慢性髓性白血病患者中报道了少数伊马替尼治疗继发皮肤SCC的病例。然而,在GIST患者中尚无关于伊马替尼相关SCC病因的临床证据。
据我们所知,本报告首次描述了接受GIST治疗的患者中与伊马替尼相关的SCC。这意味着伊马替尼在GIST患者中的安全性和长期耐受性需要严格检测及密切监测。