Gleave M E, Elhilali M, Fradet Y, Davis I, Venner P, Saad F, Klotz L H, Moore M J, Paton V, Bajamonde A
Vancouver Hospital and Health Sciences Centre, University of British Columbia, Canada.
N Engl J Med. 1998 Apr 30;338(18):1265-71. doi: 10.1056/NEJM199804303381804.
Most trials of immunomodulators in metastatic renal-cell carcinoma have been uncontrolled and subject to selection bias. The objective of this blinded, placebo-controlled study was to compare overall response rates, time to disease progression, and survival of patients with metastatic renal-cell carcinoma treated with recombinant human interferon gamma-1b or placebo.
Patients with biopsy-proved metastatic renal-cell carcinoma were randomly assigned to receive interferon gamma-1b (60 microg per square meter of body-surface area subcutaneously once weekly) or placebo. The primary tumor had been treated by nephrectomy or angioinfarction at least three weeks previously. Patients were evaluated for radiologic evidence of progression, and all responses were independently reviewed by a committee that was unaware of the treatment.
A total of 197 patients with metastatic renal-cell carcinoma were enrolled at 17 centers in Canada. One hundred eighty-one patients could be evaluated; of these, 91 were assigned to receive interferon gamma-1b and 90 were given placebo. The groups were well balanced in terms of prognostic factors. Two thirds of all patients had Karnofsky scores of 90 or 100, and more than half had two or more metastatic sites. Grade I and II toxicity, mostly chills, fever, asthenia, or headaches, was reported in 91 percent and 61 percent, respectively, of the patients in the interferon group, as compared with 76 percent and 63 percent in the placebo group. Life-threatening drug-related events were rare, occurring in 1 percent of patients in the interferon group. No significant differences between groups were observed in overall response rates, time to disease progression, or survival. The overall response rate was 4.4 percent (3.3 percent complete response and 1.1 percent partial response) in the interferon group and 6.6 percent (3.3 percent complete response and 3.3 percent partial response) in the placebo group (P=0.54), with a rate of durable complete response of 1 percent in both groups. The median time to disease progression was 1.9 months in both groups (P=0.49), and there was no significant difference in median survival (12.2 months with interferon vs. 15.7 months with placebo, P=0.52).
No difference in outcome was observed in patients with metastatic renal-cell carcinoma who were treated with interferon gamma-1b as compared with placebo. These results emphasize the necessity of testing the efficacy of immunomodulators in randomized studies.
大多数转移性肾细胞癌免疫调节剂试验缺乏对照且存在选择偏倚。这项双盲、安慰剂对照研究的目的是比较接受重组人干扰素γ-1b或安慰剂治疗的转移性肾细胞癌患者的总缓解率、疾病进展时间和生存率。
经活检证实为转移性肾细胞癌的患者被随机分配接受干扰素γ-1b（每平方米体表面积60微克，皮下注射，每周一次）或安慰剂。原发肿瘤至少在三周前已通过肾切除术或血管梗死术进行治疗。评估患者疾病进展的影像学证据，所有缓解情况均由一个不知情的委员会独立审查。
加拿大17个中心共纳入197例转移性肾细胞癌患者。181例患者可进行评估；其中，91例被分配接受干扰素γ-1b治疗，90例接受安慰剂治疗。两组在预后因素方面均衡良好。所有患者中有三分之二的卡诺夫斯基评分在90或100分，半数以上患者有两个或更多转移部位。干扰素组分别有91%和61%的患者报告了I级和II级毒性反应，主要为寒战、发热、乏力或头痛，而安慰剂组分别为76%和63%。危及生命的药物相关事件罕见，在干扰素组中占1%的患者。两组在总缓解率、疾病进展时间或生存率方面未观察到显著差异。干扰素组的总缓解率为4.4%（完全缓解率为3.3%，部分缓解率为1.1%），安慰剂组为6.6%（完全缓解率为3.3%，部分缓解率为3.3%）（P = 0.54），两组的持久完全缓解率均为1%。两组的疾病进展中位时间均为1.9个月（P = 0.49），中位生存期无显著差异（干扰素组为12.2个月，安慰剂组为15.7个月，P = 0.52）。
与安慰剂相比，接受干扰素γ-1b治疗的转移性肾细胞癌患者在结局方面未观察到差异。这些结果强调了在随机研究中测试免疫调节剂疗效的必要性。
