Kozin S V, Boucher Y, Hicklin D J, Bohlen P, Jain R K, Suit H D
Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston 02114, USA.
Cancer Res. 2001 Jan 1;61(1):39-44.
Antiangiogenic therapy can enhance radiation-induced tumor growth inhibition. However, the effects of combined antiangiogenic and radiation therapy on long-term tumor control and normal tissue response have not been reported. We treated mice bearing two different human tumor xenografts with anti-vascular endothelial growth factor receptor-2 antibody (DC101) and five dose fractions of local radiation and followed them for at least 6 months. DC101 significantly decreased the dose of radiation necessary to control 50% of tumors locally. The decrease was 1.7- and 1.3-fold for the moderately radiosensitive small cell lung carcinoma 54A and the highly radioresistant glioblastoma multiforme U87, respectively. In contrast to tumors, no increase in skin radiation reaction by the antibody was detected. Surprisingly, 44% of mice bearing 54A tumor developed clear ascites after DC101 treatment at its highest dose; this was fatal to 20% of mice. This adverse effect was seen only in mice that received whole-body irradiation 1 day before tumor implantation. The encouraging results on two human tumor xenografts suggest that vascular endothelial growth factor receptor-2 blockade merits further investigation to assess its potential as an enhancer of radiation therapy in the clinic.
抗血管生成疗法可增强辐射诱导的肿瘤生长抑制作用。然而，抗血管生成与放射治疗联合应用对长期肿瘤控制和正常组织反应的影响尚未见报道。我们用抗血管内皮生长因子受体-2抗体（DC101）和五个剂量分割的局部放疗对荷有两种不同人肿瘤异种移植物的小鼠进行治疗，并对它们进行了至少6个月的随访。DC101显著降低了局部控制50%肿瘤所需的辐射剂量。对于中度放射敏感的小细胞肺癌54A和高度放射抗性的多形性胶质母细胞瘤U87，该降低倍数分别为1.7倍和1.3倍。与肿瘤情况相反，未检测到抗体导致皮肤辐射反应增加。令人惊讶的是，荷有54A肿瘤的小鼠中，44%在接受最高剂量DC101治疗后出现明显腹水；其中20%的小鼠因此死亡。这种不良反应仅在肿瘤植入前1天接受全身照射的小鼠中出现。在两种人肿瘤异种移植物上取得的令人鼓舞的结果表明，血管内皮生长因子受体-2阻断值得进一步研究，以评估其在临床上作为放射治疗增强剂的潜力。
