Wadler S
Department of Oncology, Montefiore Medical Center, Bronx, New York 10467.
Cancer. 1992 Aug 15;70(4 Suppl):949-58.
Originally described as antiviral agents, interferons (IFN) were investigated as potential anticancer agents because of their antiproliferative and cytotoxic effects, their ability to activate specific components of the immune system, and their relatively modest toxicities. Interest intensified when durable complete remissions were observed in patients with hairy cell leukemia after IFN treatment; modest, but reproducible activity also was found against tumors such as melanoma and renal cell carcinoma which are unresponsive to conventional chemotherapy. Observations of synergy between IFN and cytotoxic drugs in vitro and in vivo suggested that IFN may have additional utility as modulating agents.
Reports of major clinical trials using IFN either alone or in combination with other agents were reviewed. Activity was identified by disease site. Correlations were made with important preclinical studies.
IFN has reproducible, but modest, single-agent activity against melanoma, renal cell carcinoma, and acquired immune deficiency syndrome-related Kaposi sarcoma. IFN may be useful in the treatment of a number of benign, in situ, or low-grade tumors. IFN in combinations with cytotoxic agents have demonstrated activity in solid tumors. Clinical trials using combinations of IFN and 5-fluorouracil or dacarbazine suggested a potential benefit for the combination compared with single-agent chemotherapy. These are preliminary findings that require confirmation, but they suggest that combination therapy should be investigated further. In early preclinical and clinical studies, combinations of IFN and other biologic agents, hormonal agents, and radiation therapy appear to be interesting.
The role of IFN in the treatment of solid tumors may be evolving from that of single-agent therapy to combination therapy with other active agents. Additional studies are required to determine the optimal doses, schedules, and sequencing of these combination therapies.
干扰素（IFN）最初被描述为抗病毒药物，由于其具有抗增殖和细胞毒性作用、激活免疫系统特定成分的能力以及相对较低的毒性，因而作为潜在的抗癌药物进行了研究。当观察到毛细胞白血病患者在接受干扰素治疗后出现持久的完全缓解时，人们的兴趣大增；同时还发现，干扰素对黑色素瘤和肾细胞癌等对传统化疗无反应的肿瘤也有一定作用，虽效果不显著，但具有可重复性。体外和体内实验观察到干扰素与细胞毒性药物之间存在协同作用，这表明干扰素作为调节剂可能具有更多用途。
回顾了单独使用干扰素或与其他药物联合使用的主要临床试验报告。根据疾病部位确定活性。并与重要的临床前研究进行了相关性分析。
干扰素对黑色素瘤、肾细胞癌和获得性免疫缺陷综合征相关的卡波西肉瘤具有可重复但作用有限的单药活性。干扰素可能对多种良性、原位或低级别肿瘤的治疗有用。干扰素与细胞毒性药物联合使用在实体瘤中已显示出活性。使用干扰素与5-氟尿嘧啶或达卡巴嗪联合的临床试验表明，与单药化疗相比，联合用药可能具有潜在益处。这些都是需要证实的初步发现，但表明联合治疗应进一步研究。在早期临床前和临床研究中，干扰素与其他生物制剂、激素制剂及放射治疗的联合似乎很有意义。
干扰素在实体瘤治疗中的作用可能正从单药治疗向与其他活性药物联合治疗演变。需要进一步研究以确定这些联合治疗的最佳剂量、方案和顺序。
