Department of Microbiology and Immunology, Institute of Biosciences, UNESP-Univ Estadual Paulista, Botucatu, São Paulo, Brazil.
Int J Cancer. 2013 Jun 1;132(11):2471-8. doi: 10.1002/ijc.27801. Epub 2012 Sep 21.
Given that cancer is one of the main causes of death worldwide, many efforts have been directed toward discovering new treatments and approaches to cure or control this group of diseases. Chemotherapy is the main treatment for cancer; however, a conventional schedule based on maximum tolerated dose (MTD) shows several side effects and frequently allows the development of drug resistance. On the other side, low dose chemotherapy involves antiangiogenic and immunomodulatory processes that help host to fight against tumor cells, with lower grade of side effects. In this review, we present evidence that metronomic chemotherapy, based on the frequent administration of low or intermediate doses of chemotherapeutics, can be better than or as efficient as MTD. Finally, we present some data indicating that noncytotoxic concentrations of antineoplastic agents are able to both up-regulate the immune system and increase the susceptibility of tumor cells to cytotoxic T lymphocytes. Taken together, data from the literature provides us with sufficient evidence that low concentrations of selected chemotherapeutic agents, rather than conventional high doses, should be evaluated in combination with immunotherapy.
鉴于癌症是全球主要死因之一，人们已经投入大量努力来寻找新的治疗方法和手段，以治愈或控制这类疾病。化疗是癌症的主要治疗方法；然而，基于最大耐受剂量 (MTD) 的常规方案会产生多种副作用，并且常常导致耐药性的产生。另一方面，低剂量化疗涉及抗血管生成和免疫调节过程，有助于宿主对抗肿瘤细胞，副作用程度较低。在这篇综述中，我们提出了证据，表明基于低剂量或中剂量化疗药物频繁给药的节拍化疗可能比 MTD 更好或同样有效。最后，我们提供了一些数据，表明非细胞毒性浓度的抗肿瘤药物既能上调免疫系统，又能增加肿瘤细胞对细胞毒性 T 淋巴细胞的敏感性。综上所述，文献中的数据为我们提供了充分的证据，表明应评估选定化疗药物的低浓度，而不是常规高剂量，与免疫疗法联合使用。
