Foon K A, Roth M S, Bunn P A
Semin Oncol. 1986 Sep;13(3 Suppl 2):35-42.
The interferons represent an important first member of a family of biologic response modifiers used in treating human malignancies. Activities associated with the interferons include inhibition of viral replication, influence on cellular protein production, direct antiproliferative effects, and a variety of modulatory effects on the immune response. These regulatory functions of interferon underlie the interest in its use as an anticancer agent. Interferon alpha is the most extensively studied interferon species. Although antitumor activity has been seen both in vivo and in vitro in some solid malignancies, the most impressive responses have occurred in the hematologic malignancies. For the low-grade non-Hodgkin's lymphomas, response rates of 50%, with 10% to 15% complete responses, have been reported. A response rate of 15% has been reported for chronic lymphocytic leukemia in studies outside of the National Cancer Institute (NCI); in our phase II trials at the NCI, only two (11%) of 18 patients had brief partial responses to recombinant interferon alpha. For patients with cutaneous T-cell lymphomas (mycosis fungoides and the Sézary syndrome), a response rate of 45%, with 10% complete responses, was seen in patients treated with recombinant interferon alpha. Based on such findings, interferon appears to be one of the most effective single agents for cutaneous T-cell lymphomas. Further phase II trials are being conducted to determine whether lower doses of interferon alpha are as effective as the high doses used in the previously reported studies. Phase III trials will involve the use of interferons in combination with chemotherapeutic agents as well as in the adjuvant setting.
干扰素是用于治疗人类恶性肿瘤的生物反应调节剂家族中重要的首个成员。与干扰素相关的活性包括抑制病毒复制、影响细胞蛋白质生成、直接的抗增殖作用以及对免疫反应的多种调节作用。干扰素的这些调节功能是其作为抗癌药物受到关注的基础。α干扰素是研究最为广泛的干扰素种类。尽管在一些实体恶性肿瘤的体内和体外实验中均观察到了抗肿瘤活性，但最显著的反应出现在血液系统恶性肿瘤中。对于低度非霍奇金淋巴瘤，据报道缓解率为50%，完全缓解率为10%至15%。在国立癌症研究所（NCI）之外的研究中，慢性淋巴细胞白血病的缓解率为15%；在我们NCI的II期试验中，18例患者中只有2例（11%）对重组α干扰素出现短暂部分缓解。对于皮肤T细胞淋巴瘤（蕈样肉芽肿和Sezary综合征）患者，接受重组α干扰素治疗的患者缓解率为45%，完全缓解率为10%。基于这些发现，干扰素似乎是治疗皮肤T细胞淋巴瘤最有效的单一药物之一。正在进行进一步的II期试验，以确定较低剂量的α干扰素是否与先前报道研究中使用的高剂量一样有效。III期试验将涉及干扰素与化疗药物联合使用以及在辅助治疗中的应用。
