Graduate Institute of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Obstetrics and Gynecology, National Taiwan University Hospital Hsin-Chu Branch, Hsin-Chu City, Taiwan; Department of Obstetrics and Gynecology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Department of Obstetrics and Gynecology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Cancer Lett. 2017 Aug 1;400:282-292. doi: 10.1016/j.canlet.2017.01.040. Epub 2017 Feb 9.
Systemic chemotherapy given at maximum tolerated doses (MTD) has been the mainstay of cancer treatment for more than half a century. In some chemosensitive diseases such as hematologic malignancies and solid tumors, MTD has led to complete remission and even cure. The combination of maintenance therapy and standard MTD also can generate good disease control; however, resistance to chemotherapy and disease metastasis still remain major obstacles to successful cancer treatment in the majority of advanced tumors. Metronomic chemotherapy, defined as frequent administration of chemotherapeutic agents at a non-toxic dose without extended rest periods, was originally designed to overcome drug resistance by shifting the therapeutic target from tumor cells to tumor endothelial cells. Metronomic chemotherapy also exerts anti-tumor effects on the immune system (immunomodulation) and tumor cells. The goal of immunotherapy is to enhance host anti-tumor immunities. Adding immunomodulators such as metronomic chemotherapy to immunotherapy can improve the clinical outcomes in a synergistic manner. Here, we review the anti-tumor mechanisms of metronomic chemotherapy and the preliminary research addressing the combination of immunotherapy and metronomic chemotherapy for cancer treatment in animal models and in clinical setting.
半个多世纪以来，以最大耐受剂量（MTD）给予的全身性化疗一直是癌症治疗的主要手段。在一些化疗敏感的疾病中，如血液恶性肿瘤和实体肿瘤，MTD 可导致完全缓解甚至治愈。维持治疗与标准 MTD 的联合应用也能很好地控制疾病；然而，在大多数晚期肿瘤中，化疗耐药和疾病转移仍然是成功治疗癌症的主要障碍。节拍化疗是指在无延长休息期的情况下，以非毒性剂量频繁给予化疗药物，最初的设计目的是通过将治疗靶点从肿瘤细胞转移到肿瘤内皮细胞来克服耐药性。节拍化疗还对免疫系统（免疫调节）和肿瘤细胞发挥抗肿瘤作用。免疫疗法的目标是增强宿主的抗肿瘤免疫。将免疫调节剂如节拍化疗与免疫疗法联合使用可以以协同的方式改善临床结果。在这里，我们回顾了节拍化疗的抗肿瘤机制，以及在动物模型和临床环境中，免疫疗法联合节拍化疗治疗癌症的初步研究。
