Phase 2 study of sunitinib in patients with metastatic mucosal or acral melanoma
Phase 2 study of sunitinib in patients with metastatic mucosal or acral melanoma
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DOI：
10.1002/cncr.29622
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发表时间：
2015-11-15
期刊：
影响因子：
6.2
通讯作者：
Hodi, F. Stephen
中科院分区：
文献类型：
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作者：
Buchbinder, Elizabeth I.;Sosman, Jeffrey A.;Hodi, F. Stephen
粘膜和肢端黑色素瘤患者的治疗选择有限，预后差。这些黑色素瘤亚型中KIT癌基因的突变提供了一个潜在的治疗靶点。METHODSA舒尼替尼多中心2期临床试验在原发于粘膜或肢端的不可切除的III期或IV期黑色素瘤患者中进行。患者分2个队列接受治疗：队列A接受舒尼替尼治疗，剂量为50 mg/d，持续4周，6周为1周期;队列B接受舒尼替尼治疗，剂量为37.5 mg/d，持续治疗。对于治疗相关的毒性，允许降低剂量，并且每2个月进行一次肿瘤评估。4例患者证实部分缓解，持续5至10个月（1例KIT突变）。在两个队列中，2个月时存活且无进展的患者比例为52%（95%置信区间，38%-66%）;这显著大于假设的零值5%。25%的KIT突变患者和无突变患者的缓解率或总生存期无显著差异（缓解率，7.7% vs 9.7%;总生存期，6.4 vs 8.6个月）。整体疾病控制率为44%，和高毒性率与treatment.CONCLUSIONSSunitinib显示活性在粘膜和肢端黑色素瘤的治疗是不依赖于存在的KIT突变。然而，药物耐受性差，没有长期反应。Cancer 2015;121：4007-4015. (c)舒尼替尼在治疗粘膜和肢端黑色素瘤中具有活性，其不依赖于KIT突变的存在。然而，这种药物的耐受性很差，没有长期的反应。
BACKGROUNDPatients with mucosal and acral melanomas have limited treatment options and a poor prognosis. Mutations of the KIT oncogene in these melanoma subtypes provide a potential therapeutic target.METHODSA multicenter phase 2 trial of sunitinib was conducted in patients with unresectable stage III or IV melanoma of a mucosal or acral primary origin. Patients were treated in 2 cohorts: cohort A received sunitinib at a dose of 50 mg daily for 4 weeks of a 6-week cycle, and cohort B received sunitinib at a dose of 37.5 mg daily on a continuous basis. Dose reductions were permitted for treatment-related toxicities, and tumor assessments were performed every 2 months.RESULTSFifty-two patients were enrolled: 21 in cohort A and 31 in cohort B. Four patients had confirmed partial responses, which lasted 5 to 10 months (1 with a KIT mutation). In both cohorts, the proportion of patients alive and progression-free at 2 months was 52% (95% confidence interval, 38%-66%); this was significantly larger than the hypothesized null of 5%. There was no significant difference in response or overall survival between the 25% of patients with a KIT mutation and those without one (response rate, 7.7% vs 9.7%; overall survival, 6.4 vs 8.6 months). The overall disease control rate was 44%, and a high rate of toxicity was associated with the treatment.CONCLUSIONSSunitinib showed activity in the treatment of mucosal and acral melanoma that was not dependent on the presence of a KIT mutation. However, the medication was poorly tolerated, and there were no prolonged responses. Cancer 2015;121:4007-4015. (c) 2015 American Cancer Society.Sunitinib has activity in the treatment of mucosal and acral melanoma that is not dependent on the presence of a KIT mutation. However, the medication is poorly tolerated, and there are no prolonged responses.