Kim K B, Eton O, Davis D W, Frazier M L, McConkey D J, Diwan A H, Papadopoulos N E, Bedikian A Y, Camacho L H, Ross M I, Cormier J N, Gershenwald J E, Lee J E, Mansfield P F, Billings L A, Ng C S, Charnsangavej C, Bar-Eli M, Johnson M M, Murgo A J, Prieto V G
Department of Melanoma Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Br J Cancer. 2008 Sep 2;99(5):734-40. doi: 10.1038/sj.bjc.6604482. Epub 2008 Aug 19.
Metastatic melanoma cells express a number of protein tyrosine kinases (PTKs) that are considered to be targets for imatinib. We conducted a phase II trial of imatinib in patients with metastatic melanoma expressing at least one of these PTKs. Twenty-one patients whose tumours expressed at least one PTK (c-kit, platelet-derived growth factor receptors, c-abl, or abl-related gene) were treated with 400 mg of imatinib twice daily. One patient with metastatic acral lentiginous melanoma, containing the highest c-kit expression among all patients, had dramatic improvement on positron emission tomographic scan at 6 weeks and had a partial response lasting 12.8 months. The responder had a substantial increase in tumour and endothelial cell apoptosis at 2 weeks of treatment. Imatinib was fairly well tolerated: no patient required treatment discontinuation because of toxicity. Fatigue and oedema were the only grade 3 or 4 toxicities that occurred in more than 10% of the patients. Imatinib at the studied dose had minimal clinical efficacy as a single-agent therapy for metastatic melanoma. However, based on the characteristics of the responding tumour in our study, clinical activity of imatinib, specifically in patients with melanoma with certain c-kit aberrations, should be examined.
转移性黑色素瘤细胞表达多种蛋白酪氨酸激酶（PTK），这些激酶被认为是伊马替尼的作用靶点。我们对表达至少一种此类PTK的转移性黑色素瘤患者进行了伊马替尼的II期试验。21例肿瘤表达至少一种PTK（c-kit、血小板衍生生长因子受体、c-abl或abl相关基因）的患者接受了每日两次400mg伊马替尼的治疗。1例转移性肢端雀斑样痣黑色素瘤患者，其c-kit表达在所有患者中最高，在6周时正电子发射断层扫描显示有显著改善，部分缓解持续了12.8个月。该反应者在治疗2周时肿瘤和内皮细胞凋亡大幅增加。伊马替尼耐受性相当良好：没有患者因毒性而需要停药。疲劳和水肿是超过10%的患者出现的仅有的3级或4级毒性反应。研究剂量的伊马替尼作为转移性黑色素瘤的单药治疗临床疗效甚微。然而，基于我们研究中反应性肿瘤的特征，应研究伊马替尼的临床活性，特别是在具有某些c-kit异常的黑色素瘤患者中。
