我们评估了联合贝伐单抗和奥曲肽注射液（temsirolimus）治疗晚期非胰腺神经内分泌肿瘤的疗效和安全性。该NCI赞助的多中心、开放标签、第II期研究（NCT01010126）招募了晚期、复发或转移的非胰腺神经内分泌肿瘤患者。所有患者均接受奥曲肽注射液和贝伐单抗治疗，直到疾病进展或不能接受的毒性反应出现为止。奥曲肽注射液以25毫克静脉注射，每个疗程的第1、8、15和22天，而贝伐单抗以10毫克/千克静脉注射，每个疗程的第1和15天。停用奥曲肽注射液或贝伐单抗并不要求停用另一种药物。主要终点为客观缓解率和6个月无进展生存率。共有59名患者参与了这项研究，其中54名患者进行了疗效和不良事件评估。虽然中位无进展生存期为7.1个月，但奥曲肽注射液的治疗中位持续时间为3.9个月，贝伐单抗的治疗中位持续时间为3.5个月。联合治疗的客观缓解率为2%，6个月无进展生存率为48%。最常见的3-4级不良事件包括疲劳（13%）、高血压（13%）和出血（13%）。约54%的患者因不良事件、拒绝进一步治疗或治疗延迟而停止治疗。研究中发生了3例死亡，其中2例是由于治疗相关的肠道穿孔引起的。鉴于贝伐单抗和奥曲肽注射液联合治疗的疗效较小且毒性增加，我们不建议在晚期非胰腺神经内分泌肿瘤患者中使用该方案。

We assessed the efficacy and safety of combining bevacizumab with temsirolimus in patients with advanced extra-pancreatic neuroendocrine tumors. This NCI-sponsored multicenter, open-label, phase II study (NCT01010126) enrolled patients with advanced, recurrent, or metastatic extra-pancreatic neuroendocrine tumors. All patients were treated with temsirolimus and bevacizumab until disease progression or unacceptable toxicity. Temsirolimus 25 mg was administered i.v. on days 1, 8, 15, and 22 and bevacizumab 10 mg/kg i.v. on days 1 and 15 of a 4-week cycle. Discontinuation of temsirolimus or bevacizumab did not require discontinuation of the other agent. The primary endpoints were objective response rate and 6-month progression-free survival rate. Fifty-nine patients were enrolled in this study, and 54 were evaluated for efficacy and adverse events. While median progression-free survival was 7.1 months, the median duration of treatment with temsirolimus was 3.9 months and that with bevacizumab was 3.5 months. The objective response rate of combination therapy was 2%, and 6-month progression-free survival was 48%. The most frequently reported grade 3-4 adverse events included fatigue (13%), hypertension (13%), and bleeding (13%). Close to 54% of the patients discontinued treatment due to adverse events, refusal of further treatment, or treatment delays. Three deaths occurred in the study, of which two were due to treatment-related bowel perforations. Given the minimal efficacy and increased toxicity seen with the combination of bevacizumab and temsirolimus, we do not recommend the use of this regimen in patients with advanced extra-pancreatic neuroendocrine tumors.