Prospective Study of Bevacizumab Plus Temozolomide in Patients With Advanced Neuroendocrine Tumors
Prospective Study of Bevacizumab Plus Temozolomide in Patients With Advanced Neuroendocrine Tumors
复制标题
DOI：
10.1200/jco.2011.40.3147
复制
发表时间：
2012-08-20
影响因子：
45.3
通讯作者：
Kulke, Matthew H.
中科院分区：
文献类型：
--
作者：
Chan, Jennifer A.;Stuart, Keith;Kulke, Matthew H.
目的靶向血管内皮生长因子（VEGF）受体的酪氨酸激酶抑制剂和靶向血管内皮生长因子（VEGF）的单克隆抗体贝伐珠单抗（bevacizumab）在神经内分泌肿瘤（NET）中具有抗肿瘤活性。替莫唑胺是达卡巴嗪的一种口服类似物，当单独给药或与其他药物联合给药时，也具有抗NET的活性。我们进行了一项II期研究，以评估替莫唑胺与贝伐单抗联合治疗局部晚期或转移性NET患者的疗效。（56%的类癌患者，44%的胰腺NETs患者）在第1天至第7天和第15天至第21天每天口服替莫唑胺150 mg/m2，以及在每个28天周期的第1天和第15天以5 mg/kg/天的剂量静脉内给予贝伐单抗。所有患者均接受预防卡氏肺孢子虫和水痘带状疱疹。患者的毒性，生化和放射学反应，survival.ResultsThe组合替莫唑胺和贝伐单抗与预期的3至4级毒性，包括淋巴细胞减少症（53%）和血小板减少症（18%）。尽管总体放射学缓解率为15%（5/34），但胰腺NETs患者（33%; 5/15）和类癌患者（0/19）的缓解率不同。中位无进展生存期为11.0个月（胰腺NETs为14.3个月，类癌为7.3个月）。中位总生存期为33.3个月（41.7个月的胰腺NETs v 18.8个月的类癌肿瘤）。ConclusionTemozolomide和贝伐单抗可以安全地管理在晚期NETs患者一起，联合治疗方案似乎有前途的胰腺NETs患者。研究评价这两种药物对观察到的抗肿瘤活性的相对贡献是必要的。
PurposeBoth tyrosine kinase inhibitors targeting the vascular endothelial growth factor (VEGF) receptor and bevacizumab, a monoclonal antibody targeting VEGF, have antitumor activity in neuroendocrine tumors (NETs). Temozolomide, an oral analog of dacarbazine, also has activity against NETs when administered alone or in combination with other agents. We performed a phase II study to evaluate the efficacy of temozolomide in combination with bevacizumab in patients with locally advanced or metastatic NETs.Patients and MethodsThirty-four patients (56% with carcinoid, 44% with pancreatic NETs) were treated with temozolomide 150 mg/m(2) orally per day on days 1 through 7 and days 15 through 21, together with bevacizumab at a dose of 5 mg/kg per day intravenously on days 1 and 15 of each 28-day cycle. All patients received prophylaxis against Pneumocystis carinii and varicella zoster. Patients were followed for toxicity, biochemical and radiologic response, and survival.ResultsThe combination of temozolomide and bevacizumab was associated with anticipated grade 3 to 4 toxicities, including lymphopenia (53%) and thrombocytopenia (18%). Although the overall radiographic response rate was 15% (five of 34), response rates differed between patients with pancreatic NETs (33%; five of 15) and those with carcinoid tumors (zero of 19). The median progression-free survival was 11.0 months (14.3 months for pancreatic NETs v 7.3 months for carcinoid tumors). The median overall survival was 33.3 months (41.7 months for pancreatic NETs v 18.8 months for carcinoid tumors).ConclusionTemozolomide and bevacizumab can be safely administered together in patients with advanced NETs, and the combination regimen appears promising for patients with pancreatic NETs. Studies evaluating the relative contributions of these two agents to the observed antitumor activity are warranted.