Randomized study of high-dose and low-dose interleukin-2 in patients with metastatic renal cancer
Randomized study of high-dose and low-dose interleukin-2 in patients with metastatic renal cancer
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DOI：
10.1200/jco.2003.02.122
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发表时间：
2003-08-15
影响因子：
45.3
通讯作者：
Rosenberg, SA
中科院分区：
文献类型：
--
作者：
Yang, JC;Sherry, RM;Rosenberg, SA
目的：这项三臂随机研究比较了接受高剂量或两种低剂量白细胞介素-2（IL-2）方案之一的转移性肾细胞癌（RCC）患者的缓解率和总生存率。具有可测量的转移性RCC和良好性能状态的患者被随机分配接受720，000 U/kg（高剂量[HD]）或72，000 U/kg（低剂量[LD]），均每8小时通过静脉（IV）推注给药。随机分配117例患者后，第三臂的低剂量每日皮下IL-2的添加，和另外283例患者被随机assigned.Results：共156例患者被随机分配到HD IV IL-2，和150例患者LD IV IL-2。LD IV IL-2的毒性较低（特别是低血压），但在任何组中均无IL-2相关死亡。HD IV IL-2的应答比例（21%）高于LD IV IL-2（13%; P = 0.048），但总体生存率无差异。皮下IL-2的应答率（10%，部分应答和完全应答）与LD IV IL-2相似，与HD IV不同（P = 0.033）。HD IV治疗完全缓解患者的缓解持久性和生存率上级LD IV治疗（P = 0.04）。结论：所有试验方案均观察到主要肿瘤消退和完全缓解。IL-2在最大剂量下具有更高的临床活性，尽管这并没有产生总体生存益处。限制IL-2治疗潜力的免疫学因素，只有一小部分患者需要进一步阐明。
Purpose : This three-arm randomized study compares response rates and overall survival of patients with metastatic renal cell cancer (RCC) receiving high-dose or one of two low-dose interleukin-2 (IL-2) regimens.Patients and Methods: Patients with measurable metastatic RCC and a good performance status were randomized to receive either 720,000 U/kg (high-dose [HD]) or 72,000 U/kg (low-dose [LD]), both given by intravenous (IV) bolus every 8 hours. After randomly assigning 117 patients, a third arm of low-dose daily subcutaneous IL-2 was added, and an additional 283 patients were randomly assigned.Results: A total of 156 patients were randomly assigned to HD IV IL-2, and 150 patients to LD IV IL-2. Toxicities were less frequent with LD IV IL-2 (especially hypotension), but there were no IL-2-related deaths in any arm. There was a higher response proportion with HD IV IL-2 (21%) versus LD IV IL-2 (13%; P =.048) but no overall survival difference. The response rate of subcutaneous IL-2 (10%, partial response and complete response) was similar to that of LD IV IL-2, differing from HD IV (P =.033). Response durability and survival in completely responding patients was superior with HD IV compared with LD IV therapy (P =.04).Conclusion: Major tumor regressions, as well as complete responses, were seen with all regimens tested. IL-2 was more clinically active at maximal doses, although this did not produce an overall survival benefit. The immunological factors which constrain the curative potential of IL-2 to only a small percentage of patients need to be further elucidated.