Department of Gastroenterologic Surgery, Division of Cancer Medicine, Graduate School of Medical Science, Kanazawa University, 13-1 Takara-machi, Kanazawa, Ishikawa, Japan.
Cancer Chemother Pharmacol. 2010 Sep;66(4):745-53. doi: 10.1007/s00280-009-1219-y. Epub 2009 Dec 24.
Vascular endothelial growth factor (VEGF) is correlated with peritoneal metastasis of gastric cancer, increasing vascular permeability accompanied by accumulation of ascites. The aim of the current study is to investigate the biodistribution of bevacizumab in a peritoneal metastatic model of gastric cancer and to clarify which is more suited to treatment of peritoneal metastasis, systemic or regional therapy.
A highly peritoneal-seeding cell line of gastric cancer, OCUM-2MD3, which exhibited high production and release of VEGF was used in this study. The biodistribution of bevacizumab was investigated using peritoneal metastatic models together with subcutaneous xenografts, and (125)I-radiolabelled bevacizumab was administrated to these models subcutaneously (s.c.) or intraperitoneally (i.p.), respectively. In addition, the anti-tumor response of bevacizumab and paclitaxel was assessed as single agents or in combination using peritoneal metastatic models.
In the analysis of biodistribution, (125)I-bevacizumab administrated i.p. indicated low peritoneal clearance. On the other hand, s.c. administration of (125)I-bevacizumab showed preferential accumulation in subcutaneous tumors and peritoneal nodules, with a high blood concentration. In peritoneal metastatic models, the effects of bevacizumab were found for both the growth inhibition of peritoneal nodules (P < 0.01) and the reduction of ascites (P < 0.05). These effects were more prominent by s.c. administration compared with i.p. administration and were increased in combination with i.p. paclitaxel.
Bevacizumab should be administrated systemically compared to regionally, and the combination with i.p. paclitaxel has a potential to be useful for patients with peritoneal metastasis of gastric cancer.
血管内皮生长因子（VEGF）与胃癌腹膜转移相关，可增加血管通透性并伴有腹水积聚。本研究旨在探讨贝伐珠单抗在胃癌腹膜转移模型中的分布情况，并阐明哪种治疗方法更适合治疗腹膜转移，是全身治疗还是局部治疗。
本研究使用了一种具有高腹膜播种能力的胃癌细胞系 OCUM-2MD3，该细胞系表现出高产量和 VEGF 的释放。通过腹膜转移模型和皮下异种移植，研究了贝伐珠单抗的分布情况，并分别皮下（s.c.）或腹腔内（i.p.）给予（125）I 标记的贝伐珠单抗。此外，还评估了贝伐珠单抗和紫杉醇单药或联合治疗腹膜转移模型的抗肿瘤反应。
在分布分析中，腹腔内给予（125）I-贝伐珠单抗表明其腹膜清除率较低。另一方面，皮下给予（125）I-贝伐珠单抗显示出优先在皮下肿瘤和腹膜结节中积累，并具有较高的血液浓度。在腹膜转移模型中，贝伐珠单抗对腹膜结节的生长抑制（P < 0.01）和腹水减少（P < 0.05）均有作用。与腹腔内给予相比，皮下给予的效果更为显著，与腹腔内紫杉醇联合使用效果更佳。
与局部治疗相比，贝伐珠单抗应进行全身治疗，与腹腔内紫杉醇联合使用可能对胃癌腹膜转移患者有一定的应用潜力。
