阿帕替尼联合替莫唑胺治疗常规治疗失败的晚期黑色素瘤的疗效分析

Efficacy of apatinib combined with temozolomide in the treatment of advanced melanoma patients after conventional treatment failure

目的探讨阿帕替尼联合替莫唑胺治疗晚期黑色素瘤的安全性及初步疗效。方法收集2016年12月至2017年5月常规治疗失败的晚期黑素瘤患者9例,分为3个剂量递增组(每组3例):替莫唑胺100 mg,阿帕替尼250 mg;替莫唑胺200 mg,阿帕替尼250 mg;替莫唑胺200 mg,阿帕替尼500 mg。每28天重复。剂量递增采用传统3+3方法,应用RECIST 1.1标准评价疗效,不良事件按照NCI-CTCAE 4.0分级。主要研究终点为安全性(剂量限制性毒性和最大耐受剂量),次要终点为客观有效率。结果 9例晚期黑素瘤患者,剂量递增完成,未观察到剂量限制性毒性,常见不良反应包括高血压(33.3%)、手足皮肤反应(33.3%)、蛋白尿(22.2%)、白细胞减少(22.2%)、恶心(22.2%)、乏力(11.1%)等,均为1~2级,最大耐受剂量目前未达到。截至2017年5月,7例患者可评价疗效,1例部分缓解(PR),4例稳定(SD),2例进展(PD),客观反应率为14.3%。结论阿帕替尼联合替莫唑胺治疗晚期黑色素瘤未观察到剂量限制性毒性,可观察到初步疗效。

Objective To investigate the safety and preliminary efficacy of apatinib combined with temozolomide in the treatment of advanced melanoma patients. Methods Nine patients with advanced melanoma after conventional treatment failures wereenrolled from December 2016 to May 2017.The patients were enrolled to three dose escalating groups（ 3 cases in each group）, with traditional 3＋3 method, temozolomidel00mg,apatinib 250 mg; temozolide 200 mg, apatinib 250 mg; temozolomide 200 mg, apatinib 500 rag, repeated every 28 days. Tumor response was evaluated by RECIST 1.1 criteria, and adverse events were graded according to NCI- CTCAE 4. 0. The primary end point was safety （ dose-limiting toxicity and maximum tolerated dose） , and the secondary endpoint was objective response. Results Dose escalation had been finished in nine patients without dose limiting toxicity （ 3 cases in each group）. Common adverse events included hypertension （ 33.3% ） , hand foot syndrome （ 33.3% ）, proteinuria （ 22. 2% ） , white blood cell de- crease （ 22. 2% ）, nausea （ 22. 2%）, fatigue （ 11.1% ）, etc. All adverse events were grade 1-2, maximum tolerated dose was not reached.Until May 2017, 7 patients could be evaluated, 1 got partial response（PR）, 4 got stable disease（SD） and 2 got progression disease（PD）, the objective response rate was 14. 3%. Conclusion Apatinib combined with temozolomide is well tolerated withoutdose-limiting toxicity, and has shown its efficacy in advanced melanoma patients.