北京腫瘤醫(yī)院腎癌黑色素瘤病區(qū)郭軍教授等新近刊發(fā)在國際權(quán)威腫瘤雜志《臨床腫瘤學(xué)期刊》（Journal of Clinical Oncology）(最新影響因子18.97)上的題為“Phase II, Open-Label, Single-Arm Trial of Imatinib Mesylate in Patients With Metastatic Melanoma Harboring c-Kit Mutation or Amplification”的報告顯示：經(jīng)Ⅱ期臨床研究證實,，伊馬替尼治療c-Kit基因突變轉(zhuǎn)移性黑色素瘤,，可獲得較高的總緩解率（23.3%）和疾病控制率（54%）。
郭軍教授及其團(tuán)隊在該項II期臨床研究中評價了43例患者（均為c-Kit基因突變或擴(kuò)增的轉(zhuǎn)移性黑色素瘤患者）總體的無疾病進(jìn)展生存（PFS）,、總反應(yīng)率（ORR）和總生存（OS）。結(jié)果顯示：6個月的無疾病進(jìn)展生存率為36.6%，中位無疾病進(jìn)展生存為3.5個月,。1年總生存率為51.0%，中位總生存為14.0個月,，PR或SD患者總生存為15個月,，疾病進(jìn)展者為9個月（P=0.036）。相關(guān)工作在2010年美國癌癥年會上進(jìn)行了專題討論,，該結(jié)果已于近期在JCO雜志正式發(fā)表,。
此前曾有三位研究者對未經(jīng)選擇的89例轉(zhuǎn)移性黑色素瘤患者使用伊馬替尼治療，結(jié)果僅有一例患者疾病緩解,。后來證明此例獲得緩解的患者是一個c-Kit基因突變的肢端黑色素瘤患者,。在郭軍教授主持的這項研究中，入組患者均為c-Kit基因突變和（或）c-Kit基因拷貝數(shù)擴(kuò)增患者,。與未經(jīng)選擇患者中進(jìn)行的試驗結(jié)果相比,，這項研究結(jié)果非常令人振奮，這些患者多為Ⅳ期、化療失敗患者,，目前尚無標(biāo)準(zhǔn)治療,。據(jù)此推論，未來可能可以將黑色素瘤患者按分子分型進(jìn)行分類,，之后再根據(jù)突變特點(diǎn)選擇合適的個體化靶向治療,，如BRAF突變患者可使用PLX4032，c-Kit突變患者可選擇伊馬替尼,，從而逐步地解決整個黑色素瘤的治療問題,。
郭軍教授的這一臨床試驗設(shè)計和結(jié)果為中國黑色素瘤患者的個體化靶向治療提供了新的思路，也向其他腫瘤治療專家及與腫瘤抗?fàn)幦巳赫宫F(xiàn)出了令人振奮的腫瘤治療前景,。（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
Guo J, Si L, Kong Y, Flaherty KT, Xu X, Zhu Y, Corless CL, Li L, Li H, Sheng X, Cui C, Chi Z, Li S, Han M, Mao L, Lin X, Du N, Zhang X, Li J, Wang B, Qin S.
PURPOSE:Melanomas harbor aberrations in the c-Kit gene. We tested the efficiency of the tyrosine kinase inhibitor imatinib in selected patients with metastatic melanoma harboring c-Kit mutations or amplifications.PATIENTS AND METHODS:Forty-three patients with metastatic melanoma harboring c-Kit aberrations were enrolled on this phase II trial. Each patient received a continuous dose of imatinib 400 mg/d unless intolerable toxicities or disease progression occurred. Fifteen patients who experienced progression of disease were allowed to escalate the dose to 800 mg/d.RESULTS:Forty-three patients were eligible for evaluation, and the median follow-up time was 12.0 months. The median progression-free survival (PFS) was 3.5 months, and the 6-month PFS rate was 36.6%. Rate of total disease control was 53.5%: 10 patients (23.3%; 95% CI, 10.2% to 36.4%) and 13 patients (30.2%; 95% CI, 16.0% to 44.4%) achieved partial response (PR) and stable disease (SD), respectively. Eighteen patients (41.9%) demonstrated regression of tumor mass. Notably, nine of the 10 PRs were observed in patients with mutations in exons 11 or 13. The 1-year overall survival (OS) rate was 51.0%. The median PFS and OS times for patients who had PR or SD versus disease progression were 9.0 months versus 1.5 months (P < .001) and 15.0 months versus 9.0 months (P = .036), respectively. Imatinib 400 mg/d was well tolerated, and only one of the 15 patients who received dose escalation to 800 mg/d achieved SD.CONCLUSION:Imatinib demonstrated significant activity in patients with metastatic melanoma harboring genetic c-Kit aberrations, with an overall response rate of 23.3%. Escalation to 800 mg/d could not restore disease control.
