Kidney cancer: The Cytokine Working Group experience (1986-2001) - Part II: Management of IL-2 toxicity and studies with other cytokines
Kidney cancer: The Cytokine Working Group experience (1986-2001) - Part II: Management of IL-2 toxicity and studies with other cytokines
复制标题
DOI：
10.1385/mo:18:3:209
复制
发表时间：
2001-01-01
期刊：
影响因子：
3.4
通讯作者：
Mier, J
中科院分区：
文献类型：
--
作者：
Dutcher, J;Atkins, MB;Mier, J
细胞因子工作组 (CWG) 最初成立于 1986 年，当时名为校外 IL-2/LAK 工作组。在国家癌症研究所 (NCI) 的资助下，CWG 的任务是确认 NCI 试点的高剂量白细胞介素 2 (IL2)/淋巴因子激活杀伤细胞 (LAK 细胞) 方案治疗肾细胞癌的疗效数据。自这些初步研究以来，CWG 进行了一系列临床试验，通常进行相关的免疫学研究，以评估联合免疫疗法，以增强 IL-2 的功效或降低毒性。随后，CWG 进行了试验，以证明低剂量门诊联合细胞因子疗法的活性，以帮助确定其在转移性肾细胞癌治疗方案中的作用。这最终导致了一项 III 期随机试验，该试验比较了高剂量 IL-2 的活性与门诊 IL-2 加干扰素 ix 的活性。 CWG 还完善了高剂量 IL-2 和门诊 IL-2 方案的管理，使这些方案在经验丰富的临床医生手中更加安全。此外，CWG 还对新细胞因子进行了一系列精心进行的临床试验，再次试图确定其作为抗癌药物的临床功效。其中包括 IL-4、IL-6 和 IL-12 的研究。目前，CWG 正在开展 IL-2 治疗新方法的研究，并计划试验治疗肾细胞癌的新药物。这篇评论描述了过去 15 年所做的这些努力。
The Cytokine Working Group (CWG) was initially established in 1986 as the Extramural IL-2/LAK Working Group. With funding from the National Cancer Institute (NCI), the CWG was mandated to confirming data regarding the efficacy of the high-dose interleukin-2 (IL2)/lymphokine-activated killer cell (LAK cell) regimen piloted at the NCI in the treatment of renal cell cancer. Since those initial studies, the CWG has conducted a series of clinical trials, often with correlative immunologic investigations, to evaluate combination immunotherapy in attempts to enhance the efficacy of IL-2 or to reduce toxicity. Subsequently, the CWG conducted trials to demonstrate the activity of lower-dose outpatient combination cytokine regimens to help determine their role in the armamentarium of treatment for metastatic renal cell cancer. This has culminated in a phase III randomized trial comparing the activity of high-dose IL-2 with the activity of outpatient IL-2 plus interferon-ix. The CWG also has honed the management of both high-dose IL-2 and outpatient IL-2 regimens to make these safer in the hands of experienced clinicians. In addition, the CWG has produced a series of carefully conducted clinical trials of new cytokines, again attempting to define their clinical efficacy as anticancer agents. These include studies of IL-4, IL-6, and IL-12. Currently, the CWG is conducting studies with new approaches to IL-2 therapy, as well as planning trials with new agents for treatment of renal cell cancer. This review describes these efforts conducted over the past 15 yr.