Law T M, Motzer R J, Mazumdar M, Sell K W, Walther P J, O'Connell M, Khan A, Vlamis V, Vogelzang N J, Bajorin D F
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
Cancer. 1995 Sep 1;76(5):824-32. doi: 10.1002/1097-0142(19950901)76:5<824::aid-cncr2820760517>3.0.co;2-n.
Treatment with interleukin-2 (IL-2) and lymphokine-activated killer cells (LAK) resulted in responses in some patients with advanced renal cell carcinoma (RCC). However, the relative therapeutic benefit of the addition of LAK to IL-2 was unknown.
A randomized Phase III trial was conducted in patients with RCC comparing continuous intravenous infusion (CI) IL-2 alone with CI IL-2 plus LAK. Interleukin-2 was administered at 3 x 10(6) U/m2/day on days 1-5, 13-17, 21-24, and 28-31. Patients on the LAK treatment arm underwent leukapheresis on days 8-10 and LAK cell reinfusion on days 13-15. The results are reported with long-term follow-up. The published experience with IL-2 alone or with the addition of LAK was investigated in a quantitative literature survey. The response proportions were studied by schedule (high dose bolus, moderate dose, low dose) and by concomitant administration of LAK.
Seventy-one patients were treated, 36 on the IL-2 arm and 35 on the IL-2 plus LAK arm. Four patients (6%) had major responses (two complete, two partial). The median survival of all patients was 13 months (95% confidence interval [CI], 9-18 months). There were no differences between treatment arms with regard to response (P = 0.61) and survival (P = 0.67). More patients on the LAK arm experienced pulmonary toxicity (P = 0.008). The overall weighted response proportion was 16% (95% CI, 8%-24%) for the 39 published series of 1291 patients treated with IL-2. The 95% confidence intervals for response proportion overlapped when compared by schedule and by administration of LAK.
The dose and schedule of IL-2 used in this study resulted in a low level of antitumor activity and the addition of LAK did not improve the response rate against RCC. Given the infrequent, but reproducible, responses with IL-2 and interferon-based regimens, continued investigation of these agents is warranted as is the study of new cytokines. Alternative treatment strategies should be studied in RCC and new agents and treatment regimens that appear promising in Phase II studies must be studied in randomized trials.
白细胞介素-2（IL-2）联合淋巴因子激活的杀伤细胞（LAK）治疗使部分晚期肾细胞癌（RCC）患者产生了反应。然而，IL-2联合LAK的相对治疗益处尚不清楚。
对RCC患者进行了一项随机III期试验，比较单纯持续静脉输注（CI）IL-2与CI IL-2加LAK的疗效。在第1 - 5天、13 - 17天、21 - 24天和28 - 31天，以3×10⁶ U/m²/天的剂量静脉输注IL-2。LAK治疗组的患者在第8 - 10天进行白细胞分离术，并在第13 - 15天回输LAK细胞。报告了长期随访结果。通过定量文献调查研究了单独使用IL-2或联合LAK的已发表经验。按给药方案（大剂量推注、中等剂量、低剂量）和LAK的联合使用情况研究了缓解率。
共治疗71例患者，IL-2组36例，IL-2加LAK组35例。4例患者（6%）出现主要反应（2例完全缓解，2例部分缓解）。所有患者的中位生存期为13个月（95%置信区间[CI]，9 - 18个月）。治疗组在反应（P = 0.61）和生存（P = 0.67）方面无差异。LAK组有更多患者出现肺部毒性（P = 0.008）。在已发表的1291例接受IL-2治疗的39个系列研究中，总体加权缓解率为16%（95% CI，8% - 24%）。按给药方案和LAK使用情况比较时，缓解率的95%置信区间相互重叠。
本研究中使用的IL-2剂量和方案导致抗肿瘤活性水平较低，添加LAK并未提高RCC的缓解率。鉴于IL-2和基于干扰素的方案虽反应不常见但可重复，有必要继续研究这些药物以及新的细胞因子。应在RCC中研究替代治疗策略，对于在II期研究中显示有前景的新药物和治疗方案，必须在随机试验中进行研究。
