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贝伐珠单抗腹腔内抑制:一种治疗恶性腹水症状的潜在方法?

Intraperitoneal VEGF inhibition using bevacizumab: a potential approach for the symptomatic treatment of malignant ascites?

机构信息

Department of Oncology/Hematology/Bone Marrow Transplantation with the Section Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

出版信息

Oncologist. 2009 Dec;14(12):1242-51. doi: 10.1634/theoncologist.2009-0109. Epub 2009 Dec 11.

Abstract

Despite overall improvements in oncological care in the palliative setting, symptomatic malignant ascites remains a severe clinical problem. This form of effusion is known to be widely resistant to established modes of systemic therapy. Accordingly, frequent paracentesis often represents the only effective way for symptom relief in patients with advanced cancer. This invasive mode of therapy, however, is often very burdensome for the patient who is already severely distressed by the underlying malignancy. Recently, the trifunctional monoclonal antibody catumaxomab given i.p. has shown symptom relief in patients with ovarian cancer and malignant ascites. On another front, the release of vascular endothelial growth factor (VEGF) by tumor cells has been identified as a main factor promoting the i.p. secretion of fluid. Accordingly, recent evidence suggests that targeting VEGF may have the potential to suspend the ascites production resulting from peritoneal metastasis. Here, we review preclinical and clinical data supporting this hypothesis. We show current evidence suggesting that the i.p. application of the anti-VEGF antibody bevacizumab, which is already in use as an i.v. therapeutic drug for a variety of tumors, might represent an effective way to prevent local fluid accumulation. Because such an effect would result in significant relief for patients, future clinical studies should stringently assess the effectiveness of this targeted therapy for the treatment of malignant i.p. effusions.

摘要

尽管在姑息治疗中肿瘤学治疗总体上有所改善,但症状性恶性腹水仍然是一个严重的临床问题。这种形式的积液已知对既定的全身治疗模式广泛耐药。因此,频繁的腹腔穿刺术通常是晚期癌症患者缓解症状的唯一有效方法。然而,这种侵入性治疗模式对于已经因潜在恶性肿瘤而严重痛苦的患者来说通常非常繁重。最近,腹腔内给予的三功能单克隆抗体 catumaxomab 已显示出对卵巢癌和恶性腹水患者的症状缓解作用。另一方面,肿瘤细胞释放血管内皮生长因子 (VEGF) 已被确定为促进腹腔内液体分泌的主要因素。因此,最近的证据表明,靶向 VEGF 可能有潜力阻止腹膜转移引起的腹水产生。在这里,我们回顾支持这一假设的临床前和临床数据。我们展示了目前的证据,表明腹腔内应用抗 VEGF 抗体贝伐单抗可能是一种有效的预防局部液体积聚的方法,贝伐单抗已作为静脉内治疗药物用于多种肿瘤。因为这种效果将为患者带来显著的缓解,所以未来的临床研究应严格评估这种靶向治疗对恶性腹腔积液的治疗效果。

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