Spiegel R J
Cancer. 1987 Feb 1;59(3 Suppl):626-31. doi: 10.1002/1097-0142(19870201)59:3+<626::aid-cncr2820591310>3.0.co;2-d.
The clinical development of the alpha interferons has now progressed through initial Phase I and II trials into extensive controlled clinical trial designs. Alpha interferon has been a prototype of other biological agents that are now in clinical development. These agents operate through fundamentally different mechanisms of action than conventional chemotherapy and have produced a unique profile of side effects as well as response patterns. Time to response is generally longer than with chemotherapy, and dose-response and schedule-dependency questions continue to be explored for most tumor types. Although response rates have been low against most solid tumors when alpha interferon is used as a single agent, it has demonstrated a surprisingly wide range of efficacy in hematologic malignancies. These include tumors of presumed B-cell, T-cell, and myeloid lineages. In some diseases, e.g., hairy cell leukemia and chronic myelogenous leukemia, alpha interferon is broadly effective; it appears to considerably reduce or occasionally eliminate the malignant clone while normalizing the peripheral blood counts in most patients. In other diseases, alpha interferon appears destined to play a major role as part of combination therapy or in maintenance or consolidation therapy. In other disease settings, alpha interferon's role continues to be explored as part of combination therapy, adjuvant therapy, or as local-regional therapy. The full potential of alpha interferon as an antineoplastic agent will not be determined for many years. In this paper, the results from the first 5 years of widespread clinical testing are reviewed.
α干扰素的临床开发现已从最初的I期和II期试验进展到广泛的对照临床试验设计阶段。α干扰素一直是目前正在进行临床开发的其他生物制剂的原型。这些制剂的作用机制与传统化疗根本不同，产生了独特的副作用和反应模式。与化疗相比，起效时间通常更长，对于大多数肿瘤类型，剂量反应和给药方案依赖性问题仍在探索中。虽然单独使用α干扰素时，对大多数实体瘤的反应率较低，但它在血液系统恶性肿瘤中显示出惊人的广泛疗效。这些包括推测为B细胞、T细胞和髓系谱系的肿瘤。在某些疾病中，如毛细胞白血病和慢性粒细胞白血病，α干扰素具有广泛的疗效；它似乎能在大多数患者中显著减少或偶尔消除恶性克隆，同时使外周血细胞计数恢复正常。在其他疾病中，α干扰素似乎注定要作为联合治疗的一部分或在维持或巩固治疗中发挥主要作用。在其他疾病情况下，α干扰素作为联合治疗、辅助治疗或局部区域治疗的一部分，其作用仍在探索中。α干扰素作为一种抗肿瘤药物的全部潜力在未来许多年内都无法确定。本文回顾了广泛临床测试头5年的结果。
