Dutcher J P, Atkins M, Fisher R, Weiss G, Margolin K, Aronson F, Sosman J, Lotze M, Gordon M, Logan T, Mier J
Albert Einstein Cancer Center/Montefiore Medical Center, Bronx, New York 10467, USA.
Cancer J Sci Am. 1997 Dec;3 Suppl 1:S73-8.
This article reviews long-term follow-up data from three phase II studies conducted by the Cytokine Working Group from 1989 to 1995 that evaluated various recombinant interleukin-2 (rIL-2) -based regimens in patients with metastatic renal cell cancer. Response rates, long-term response duration, and toxicity are compared.
The Cytokine Working Group studies reviewed here investigated the safety and efficacy of two high-dose intravenous rIL-2-based regimens and two moderate-dose outpatient subcutaneous rIL-2-based regimens in patients with progressive metastatic renal cell cancer. A randomized phase II study, initiated in 1989, investigated the safety and efficacy of high-dose intravenous rIL-2 alone and high-dose intravenous rIL-2 plus recombinant interferon-alpha (rIFN-alpha). A second phase II study, initiated in 1992, tested the safety and efficacy of moderate-dose subcutaneous rIL-2 plus subcutaneous rIFN-alpha in the outpatient setting. The third trial, initiated in 1995, investigated a regimen consisting of the previous subcutaneous rIL-2 plus rIFN-alpha regimen alternating with intravenous bolus 5-fluorouracil (5-FU) plus subcutaneous rIFN-alpha. Median follow-up for these studies is 72 months, 48 months, and 24 months, respectively.
The overall response rates observed with each of these regimens were similar (17% with high-dose rIL-2 alone, 11% with high-dose rIL-2/rIFN-alpha, 17% with outpatient subcutaneous rIL-2/rIFN-alpha, and 16% with outpatient rIL-2/rIFN-alpha, plus 5-FU/rIFN-alpha). However, the high-dose rIL-2 regimen produced a 7% complete response rate, compared with 0%, 4%, and 4%, respectively, with each of the other regimens. Median response duration was also much longer with high-dose intravenous rIL-2 alone (53 months), compared with 7 months, 12 months, and 9 months, respectively, with each of the other regimens.
Complete response rate and response duration appear to favor the high-dose intravenous rIL-2 regimen. This will require verification in a randomized study comparing the best high-dose arm (rIL-2 alone) with the best outpatient regimen (rIL-2/IFN-alpha). The Cytokine Working Group is currently conducting such a study.
本文回顾了细胞因子工作组在1989年至1995年进行的三项II期研究的长期随访数据，这些研究评估了转移性肾细胞癌患者中各种基于重组白细胞介素-2（rIL-2）的治疗方案。比较了缓解率、长期缓解持续时间和毒性。
本文回顾的细胞因子工作组研究调查了两种基于高剂量静脉注射rIL-2的方案和两种基于中等剂量门诊皮下注射rIL-2的方案在进展期转移性肾细胞癌患者中的安全性和有效性。一项始于1989年的随机II期研究，调查了单独使用高剂量静脉注射rIL-2以及高剂量静脉注射rIL-2加重组干扰素-α（rIFN-α）的安全性和有效性。第二项II期研究始于1992年，测试了门诊环境下中等剂量皮下注射rIL-2加皮下注射rIFN-α的安全性和有效性。第三项试验始于1995年，研究了由先前的皮下rIL-2加rIFN-α方案与静脉推注5-氟尿嘧啶（5-FU）加皮下rIFN-α交替组成的治疗方案。这些研究的中位随访时间分别为72个月、48个月和24个月。
这些方案中每种方案观察到的总体缓解率相似（单独使用高剂量rIL-2为17%，高剂量rIL-2/rIFN-α为11%，门诊皮下rIL-2/rIFN-α为17%，门诊rIL-2/rIFN-α加5-FU/rIFN-α为16%）。然而，高剂量rIL-2方案产生了7%的完全缓解率，而其他方案分别为0%、4%和4%。单独使用高剂量静脉注射rIL-2的中位缓解持续时间也长得多（53个月），而其他方案分别为7个月、12个月和9个月。
完全缓解率和缓解持续时间似乎有利于高剂量静脉注射rIL-2方案。这需要在一项随机研究中进行验证，该研究将最佳高剂量组（单独使用rIL-2）与最佳门诊方案（rIL-2/IFN-α）进行比较。细胞因子工作组目前正在进行这样一项研究。
