Abdel-Rahman Omar, Fouad Mona
Clinical Oncology Department, Faculty of Medicine, Ain Shams University, Lotfy Elsayed Street, 11665, Cairo, Egypt,
J Cancer Res Clin Oncol. 2015 Feb;141(2):295-305. doi: 10.1007/s00432-014-1757-5. Epub 2014 Jul 3.
Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) consist of a large heterogeneous group of epithelial tumors with neuroendocrine differentiation that arises in gastrointestinal tract and pancreatic tissues. Advanced GEP-NENs are considered distinct disease entity with limited approved treatment options and poor prognosis. So, we will explore in this systematic review the value of using bevacizumab-based combination in this subset of NENs.
PubMed, Medline, the Cochrane Library, trip database and Google Scholar were searched using the terms "GEP-NENs" OR "Gastroenteropancreatic neuroendocrine tumors" AND "systemic anticancer therapy" AND "Bevacizumab" and selecting only the English literature. Outcomes of interest included progression-free survival and overall survival (PFS and OS), tumor response and toxicities.
A total of 17 potentially relevant trials were identified, of which eight studies were excluded. Hence, nine trials involving 320 patients were included. Median PFS was reported in eight out of the nine studies ranging from 8.2 to 16.5 months. Median OS was reported in one study, and it was 33.3 months for the whole group. The disease control rate was reported in the seven studies, and it ranged from 80 to 96%. The overall response rate was reported in eight studies, and it ranged from 0 to 64%. Frequently reported grade 3/4 toxicities were gastrointestinal toxicities, mucocutaneous toxicities and hematologic toxicities (particularly leucopenia).
The current evidence from the available clinical trials suggests that bevacizumab in combination with some other anticancer agents (especially mTOR inhibitors and interferons) could be a more effective and tolerable treatment for advanced GEP-NENs in the future. However, such bevacizumab-based combination cannot be recommended outside the setting of clinical trials.
胃肠胰神经内分泌肿瘤（GEP-NENs）是一大类异质性上皮性肿瘤，具有神经内分泌分化，起源于胃肠道和胰腺组织。晚期GEP-NENs被认为是一种独特的疾病实体，获批的治疗选择有限，预后较差。因此，我们将在本系统评价中探讨在这一亚组神经内分泌肿瘤中使用以贝伐单抗为基础的联合治疗的价值。
使用“GEP-NENs”或“胃肠胰神经内分泌肿瘤”以及“全身抗癌治疗”和“贝伐单抗”等检索词，在PubMed、Medline、Cochrane图书馆、trip数据库和谷歌学术中进行检索，仅选择英文文献。感兴趣的结局包括无进展生存期和总生存期（PFS和OS）、肿瘤反应和毒性。
共识别出17项潜在相关试验，其中8项研究被排除。因此，纳入了9项涉及320例患者的试验。9项研究中有8项报告了中位PFS，范围为8.2至16.5个月。1项研究报告了中位OS，全组为33.3个月。7项研究报告了疾病控制率，范围为80%至96%。8项研究报告了总体缓解率，范围为0至64%。常见的3/4级毒性反应为胃肠道毒性、皮肤黏膜毒性和血液学毒性（尤其是白细胞减少）。
现有临床试验的当前证据表明，未来贝伐单抗与其他一些抗癌药物（尤其是mTOR抑制剂和干扰素）联合使用可能是晚期GEP-NENs更有效且耐受性更好的治疗方法。然而，在临床试验之外，不推荐使用这种以贝伐单抗为基础的联合治疗。
