Sarah Cannon Research Institute, Nashville, TN 37203, USA.
Cancer. 2010 Sep 1;116(17):4122-9. doi: 10.1002/cncr.25320.
In this phase 2 study, the activity and tolerability of the combination of bevacizumab, an inhibitor of angiogenesis, and everolimus, an inhibitor of the mammalian target of rapamycin (mTOR), was evaluated in the treatment of patients with metastatic melanoma.
Patients with metastatic melanoma who had received up to 2 previous systemic regimens (chemotherapy and/or immunotherapy) were eligible. Previous treatment with angiogenesis or mTOR inhibitors was not allowed. All patients received bevacizumab at a dose of 15 mg/kg intravenously every 21 days and everolimus at a dose of 10 mg orally daily. Patients were re-evaluated every 6 weeks; those with an objective response or stable disease (according to Response Evaluation Criteria in Solid Tumors [RECIST]) continued therapy until tumor progression or unacceptable toxicity occurred.
Fifty-seven patients with metastatic melanoma received a median of 4 treatment cycles (range, 1-14+ cycles). Seven patients (12%) achieved major responses, whereas 33 patients (58%) were found to have stable disease at the time of first evaluation. The median progression-free and overall survivals were 4 months and 8.6 months, respectively. Approximately 43% of patients were alive after 12 months of follow-up. The treatment regimen was well tolerated by the majority of patients.
The combination of bevacizumab and everolimus was found to have moderate activity and was well tolerated in the treatment of patients with metastatic melanoma. Further exploration of agents with these mechanisms of action is indicated, perhaps in combination with inhibitors of the mitogen-activated protein kinase (MAPK) pathway.
在这项 2 期研究中，评估了贝伐珠单抗（一种血管生成抑制剂）联合依维莫司（一种哺乳动物雷帕霉素靶蛋白（mTOR）抑制剂）在治疗转移性黑色素瘤患者中的活性和耐受性。
符合条件的患者为转移性黑色素瘤患者，他们接受了最多 2 种先前的全身治疗方案（化疗和/或免疫治疗）。不允许以前接受过血管生成或 mTOR 抑制剂治疗。所有患者均接受贝伐珠单抗 15mg/kg 静脉注射，每 21 天一次，依维莫司 10mg 口服，每日一次。患者每 6 周重新评估一次；那些有客观反应或疾病稳定（根据实体瘤反应评估标准[RECIST]）的患者继续治疗，直到肿瘤进展或出现不可接受的毒性。
57 名转移性黑色素瘤患者接受了中位数为 4 个治疗周期（范围 1-14+个周期）的治疗。7 名患者（12%）达到了主要反应，而 33 名患者（58%）在首次评估时发现疾病稳定。中位无进展生存期和总生存期分别为 4 个月和 8.6 个月。大约 43%的患者在 12 个月的随访后仍然存活。大多数患者对治疗方案耐受良好。
贝伐珠单抗联合依维莫司在治疗转移性黑色素瘤患者中具有中等活性，且耐受性良好。进一步探索具有这些作用机制的药物是必要的，也许可以与丝裂原活化蛋白激酶（MAPK）途径抑制剂联合使用。
