Itri L M
R. W. Johnson Pharmaceutical Research Institute, Raritan, New Jersey 08869.
Cancer. 1992 Aug 15;70(4 Suppl):940-5.
In the 10 years since the interferons (IFN) entered large-scale clinical trials, much has been learned much about their uses as single agents. alpha-IFN, the most widely studied, has shown antitumor and antiviral efficacy against various tumors and tumor-related viruses; it has been approved by the Food and Drug Administration for the treatment of patients with hairy cell leukemia, acquired immune deficiency syndrome-related Kaposi sarcoma, and condylomata acuminata. Although IFN are effective as single agents in certain clinical situations, increasing experience with these cytokines suggests that their greatest therapeutic potential may be in combination with other biologic response-modifying, cytotoxic, or antiviral drugs. Trials combining alpha-IFN with 5-fluorouracil to treat colorectal carcinoma or with zidovudine to treat acquired immune deficiency syndrome have shown the significant impact that IFN administered in conjunction with other carefully selected agents can have. To design the most effective combination regimens, better preclinical models that clarify the mechanisms of action of IFN and define their biochemical interactions with other agents are needed.
自干扰素(IFN)进入大规模临床试验的10年来,人们对其作为单一药物的用途已有了很多了解。α-干扰素是研究最为广泛的,已显示出对各种肿瘤和肿瘤相关病毒具有抗肿瘤和抗病毒功效;它已被美国食品药品监督管理局批准用于治疗毛细胞白血病、获得性免疫缺陷综合征相关的卡波西肉瘤和尖锐湿疣患者。尽管干扰素在某些临床情况下作为单一药物有效,但对这些细胞因子的经验不断增加表明,它们最大的治疗潜力可能在于与其他生物反应调节剂、细胞毒性药物或抗病毒药物联合使用。将α-干扰素与5-氟尿嘧啶联合用于治疗结直肠癌或与齐多夫定联合用于治疗获得性免疫缺陷综合征的试验表明,与其他精心挑选的药物联合使用干扰素可产生显著影响。为了设计出最有效的联合治疗方案,需要更好的临床前模型来阐明干扰素的作用机制,并确定它们与其他药物的生化相互作用。