文章：

节律化疗的抗血管生成基础

The anti-angiogenic basis of metronomic chemotherapy

原文发布日期：2004-06-01

DOI: 10.1038/nrc1369

类型: Review Article

开放获取: 否

要点：

1. Conventional cytotoxic anticancer drugs have anti-angiogenic effects, which could contribute to their antitumour efficacy.
2. The anti-angiogenic effects of chemotherapy seem to be optimized by administering such drugs 'metronomically' — in small doses on a frequent schedule (daily, several times a week, or weekly) in an uninterrupted manner, for prolonged periods.
3. Conventional chemotherapy, which is administered at more toxic 'maximum tolerated doses', requires 2–3-week breaks between successive cycles of therapy. This seems to counteract the potential for sustained, therapeutically effective anti-angiogenic effects.
4. In preclinical models, metronomic chemotherapy can be effective in treating tumours in which the cancer cells have developed resistance to the same chemotherapeutics. This also has the advantage of being less acutely toxic, therefore making more prolonged treatments possible.
5. The efficacy of metronomic chemotherapy can be significantly increased when administered in combination with anti-angiogenic drugs, such as antibodies against vascular endothelial growth factor (VEGF) or VEGF receptor 2.
6. Some metronomic-chemotherapy regimens induce sustained suppression of circulating endothelial progenitor cells and increase the levels of the endogenous angiogenesis inhibitor thrombospondin 1, both of which can suppress neovascularization.
7. Clinical trials are under way to test several combinations of metronomic chemotherapy and anti-angiogenic drugs.

要点翻译：

1. 传统细胞毒性抗癌药物具有抗血管生成作用，这有助于其抗肿瘤功效。
2. 通过"节拍式"给药方式——即长期、不间断地以小剂量频繁给药（每日、每周数次或每周），可优化化疗的抗血管生成效果。
3. 传统化疗采用毒性更强的"最大耐受剂量"给药，需要在连续治疗周期之间间隔2-3周。这种方式似乎会抵消持续有效的抗血管生成治疗潜力。
4. 在临床前模型中，节拍式化疗可有效治疗对相同化疗药物产生耐药性的肿瘤。该方法还具有急性毒性较低的优势，因此可实现更长期的治疗。
5. 当与抗血管生成药物（如抗血管内皮生长因子或VEGF受体2抗体）联合使用时，节拍式化疗的疗效可显著增强。
6. 某些节拍式化疗方案能持续抑制循环内皮祖细胞，并提高内源性血管生成抑制剂血小板反应蛋白1的水平，这两者都能抑制新生血管形成。
7. 目前正在进行临床试验，以测试多种节拍式化疗与抗血管生成药物的联合方案。

英文摘要：

In addition to proliferating cancer cells and various types of normal cells, such as those of the bone marrow, conventional cytotoxic chemotherapeutics affect the endothelium of the growing tumour vasculature. The anti-angiogenic efficacy of chemotherapy seems to be optimized by administering comparatively low doses of drug on a frequent or continuous schedule, with no extended interruptions — sometimes referred to as 'metronomic' chemotherapy. In addition to reduced acute toxicity, the efficacy of metronomic chemotherapy seems to increase when administered in combination with specific anti-angiogenic drugs. Gaining better insight into the mechanisms of these effects could lessen or even eliminate the empiricism used to determine the optimal dose and schedule for metronomic chemotherapy regimens.

摘要翻译： 

除了快速增殖的癌细胞和骨髓等多种正常细胞外，传统细胞毒类化疗药物还会影响正在生长的肿瘤血管内皮。所谓“节拍”化疗，即以较低剂量、频繁或持续给药、无长时间中断的方案，似乎能最大化化疗的抗血管生成效果。与特定抗血管生成药物联合应用时，节拍化疗不仅急性毒性降低，疗效也似乎增强。若能更深入地理解其作用机制，或可减少甚至消除目前确定节拍化疗最佳剂量与方案时依赖的经验主义。

原文链接：

The anti-angiogenic basis of metronomic chemotherapy