Turco Luigi Carlo, Ferrandina Gabriella, Vargiu Virginia, Cappuccio Serena, Fagotti Anna, Sallustio Giuseppina, Scambia Giovanni, Cosentino Francesco
Mater Olbia Hospital, Gynaecology and Breast Unit, Olbia.
Division of Gynecologic Oncology, Gemelli-Molise, Università Cattolica del Sacro Cuore, Campobasso, Italia.
Ann Transl Med. 2020 Dec;8(24):1687. doi: 10.21037/atm-20-4448.
In patients undergoing debulking surgery for ovarian cancer (OC), bevacizumab-combined chemotherapy has been reported to be associated with an increased incidence of adverse events (AEs). Reports in the literature have noted the overall morbidity of bevacizumab to be between 3.7% and 9%. The aim of this study is to report uncommon and unusual manifestations of morbidity in surgical cases performed at our third level referral centers for gynecologic oncology. Additionally, we review the rare and severe bevacizumab-related complications that have been described in the literature. We defined as "extreme", the particularly rare and/or severe complications up to determining a life-threatening condition or death, which are related to the use of bevacizumab. A case-series of extreme complications registered at our institutions were reported. In addition, a literature search of the PubMed, MEDLINE and EMBASE electronic databases was performed for this review. The studies collected included: 8 randomized controlled trials (RCT) and 5 prospective observational, 1 prospective phase-IV, 10 prospective phase-II, 2 prospective phase-I, and 20 retrospective studies, as well as 9 case reports. Bevacizumab was administered as primary treatment in adjuvant and neo-adjuvant setting in 16 and 5 studies respectively, as treatment for recurrence in 36 trials, and for secondary cytoreductive surgery (SCS) in 3 studies. The overall population administered with bevacizumab numbered 7,096 women. Extreme complications were observed in 591 patients, with a morbidity rate of the 8.3%. Overall, central nervous system (CNS), cardiovascular, gastrointestinal (GI) and primary infectious complications were seen in 22 patients (0.3%), 261 patients (3.7%), 159 patients (2.2%), and 8 patients (0.13%), respectively. Hemorrhagic and wound complications occurred in 18 women (0.25%), and 112 women (1.6%), respectively. Extreme complications related to the use of bevacizumab are rare, and often go unrecognized. The recognition and immediate management of such rare and life-threatening complications in patients treated at third level referral centers could significantly improve patient survival.
在接受卵巢癌（OC）减瘤手术的患者中，据报道贝伐单抗联合化疗与不良事件（AE）发生率增加有关。文献报道指出，贝伐单抗的总体发病率在3.7%至9%之间。本研究的目的是报告在我们的三级妇科肿瘤转诊中心进行的手术病例中不常见和异常的发病表现。此外，我们回顾了文献中描述的罕见且严重的贝伐单抗相关并发症。我们将与使用贝伐单抗相关的特别罕见和/或严重的并发症定义为“极端”并发症，这些并发症直至确定为危及生命的状况或导致死亡。报告了我们机构记录的一系列极端并发症病例。此外，为进行本综述，我们对PubMed、MEDLINE和EMBASE电子数据库进行了文献检索。收集的研究包括：8项随机对照试验（RCT）、5项前瞻性观察性研究、1项前瞻性IV期研究、10项前瞻性II期研究、2项前瞻性I期研究和20项回顾性研究，以及9篇病例报告。在16项和5项研究中，贝伐单抗分别作为辅助和新辅助治疗的主要用药，在36项试验中用于复发治疗，在3项研究中用于二次减瘤手术（SCS）。接受贝伐单抗治疗的总人数为7096名女性。591名患者出现极端并发症，发病率为8.3%。总体而言，中枢神经系统（CNS）、心血管、胃肠道（GI）和原发性感染并发症分别见于22名患者（0.3%）、261名患者（3.7%）、159名患者（2.2%）和8名患者（0.13%）。出血和伤口并发症分别发生在18名女性（0.25%）和112名女性（1.6%）中。与使用贝伐单抗相关的极端并发症很罕见，且常常未被识别。在三级转诊中心接受治疗的患者中，识别并立即处理此类罕见且危及生命的并发症可显著提高患者生存率。
