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北京肿瘤医院肾癌黑色素瘤病区郭军教授等新近刊发在国际权威肿瘤杂志Journal of Clinical Oncology(JCO)(最新影响因子18.97)上的题为《Phase II, Open-Label, Single-Arm Trial of Imatinib Mesylate in Patients With Metastatic Melanoma Harboring c-Kit Mutation or Amplification》的报告显示:经Ⅱ期临床研究证实,伊马替尼治疗c-Kit基因突变转移性黑色素瘤,可获得较高的总缓解率(23.3%)和疾病控制率(54%)。
郭军教授及其团队在该项II期临床研究中评价了43例患者(均为c-Kit基因突变或扩增的转移性黑色素瘤患者)总体的无疾病进展生存(PFS)、总反应率(ORR)和总生存(OS)。结果显示:6个月的无疾病进展生存率为36.6%,中位无疾病进展生存为3.5个月。1年总生存率为51.0%,中位总生存为14.0个月,PR或SD患者总生存为15个月,疾病进展者为9个月(P=0.036)。相关工作在2010年美国癌症年会上进行了专题讨论,该结果已于近期在JCO杂志正式发表。
此前曾有三位研究者对未经选择的89例转移性黑色素瘤患者使用伊马替尼治疗,结果仅有一例患者疾病缓解。后来证明此例获得缓解的患者是一个c-Kit基因突变的肢端黑色素瘤患者。在郭军教授主持的这项研究中,入组患者均为c-Kit基因突变和(或)c-Kit基因拷贝数扩增患者。与未经选择患者中进行的试验结果相比,这项研究结果非常令人振奋,这些患者多为Ⅳ期、化疗失败患者,目前尚无标准治疗。据此推论,未来可能可以将黑色素瘤患者按分子分型进行分类,之后再根据突变特点选择合适的个体化靶向治疗,如BRAF突变患者可使用PLX4032,c-Kit突变患者可选择伊马替尼,从而逐步地解决整个黑色素瘤的治疗问题。
郭军教授的这一临床试验设计和结果为中国黑色素瘤患者的个体化靶向治疗提供了新的思路,也向其他肿瘤治疗专家及与肿瘤抗争人群展现出了令人振奋的肿瘤治疗前景。(生物谷 Bioon.com)
doi:10.1200/JCO.2010.33.9275
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Phase II, Open-Label, Single-Arm Trial of Imatinib Mesylate in Patients With Metastatic Melanoma Harboring c-Kit Mutation or Amplification
Jun Guo, Lu Si, Yan Kong, Keith T. Flaherty, Xiaowei Xu, Yanyan Zhu, Christopher L. Corless, Li Li, Haifu Li, Xinan Sheng, Chuanliang Cui, Zhihong Chi, Siming Li, Mei Han, Lili Mao, Xuede Lin, Nan Du, Xiaoshi Zhang, Junling Li, Baocheng Wang and Shukui Qin
Many persistent pain states (pain lasting for hours, days, or longer) are poorly treated because of the limitations of existing therapies. Analgesics such as nonsteroidal anti-inflammatory drugs and opioids often provide incomplete pain relief and prolonged use results in the development of severe side effects. Identification of the key mediators of various types of pain could improve such therapies. Here, we tested the hypothesis that hitherto unrecognized cytokines and chemokines might act as mediators in inflammatory pain. We used ultraviolet B (UVB) irradiation to induce persistent, abnormal sensitivity to pain in humans and rats. The expression of more than 90 different inflammatory mediators was measured in treated skin at the peak of UVB-induced hypersensitivity with custom-made