Negrier S, Escudier B, Lasset C, Douillard J Y, Savary J, Chevreau C, Ravaud A, Mercatello A, Peny J, Mousseau M, Philip T, Tursz T
Department of Medical Oncology, Centre Léon Bérard, Lyons, France.
N Engl J Med. 1998 Apr 30;338(18):1272-8. doi: 10.1056/NEJM199804303381805.
Recombinant human interleukin-2 (aldesleukin) and recombinant human interferon alfa can induce notable tumor regression in a limited number of patients with metastatic renal-cell carcinoma. We conducted a multicenter, randomized trial to determine the effect of each cytokine independently and in combination, and to identify patients who are best suited for this treatment.
Four hundred twenty-five patients with metastatic renal-cell carcinoma were randomly assigned to receive either a continuous intravenous infusion of interleukin-2, subcutaneous injections of interferon alfa-2a, or both. The main outcome measure was the response rate; secondary outcomes were the rates of event-free and overall survival. Predictive factors for response and rapid progression were identified by multivariate analysis.
Response rates were 6.5 percent, 7.5 percent, and 18.6 percent (P<0.01) for the groups receiving interleukin-2, interferon alfa-2a, and interleukin-2 plus interferon alfa-2a, respectively. At one year, the event-free survival rates were 15 percent, 12 percent, and 20 percent, respectively (P=0.01). There was no significant difference in overall survival among the three groups. Toxic effects of therapy were more common in patients receiving interleukin-2 than in those receiving interferon alfa-2a. Response to treatment was associated with having metastasis to a single organ and with receiving the combined treatment. The probability of rapid progression of disease was at least 70 percent for patients with at least two metastatic sites, liver metastases, and a period of less than one year between the diagnosis of the primary tumor and the appearance of metastases.
Cytokines are active in a few patients with metastatic renal-cell carcinoma. The higher response rate and longer event-free survival obtained with a combination of cytokines must be balanced against the toxicity of such treatment.
重组人白细胞介素-2（阿地白介素）和重组人干扰素α可使少数转移性肾细胞癌患者出现显著的肿瘤消退。我们进行了一项多中心随机试验，以确定每种细胞因子单独使用及联合使用的效果，并确定最适合这种治疗的患者。
425例转移性肾细胞癌患者被随机分配接受持续静脉输注白细胞介素-2、皮下注射干扰素α-2a或两者联合使用。主要结局指标为缓解率；次要结局为无事件生存率和总生存率。通过多变量分析确定缓解和快速进展的预测因素。
接受白细胞介素-2、干扰素α-2a和白细胞介素-2加干扰素α-2a治疗的组的缓解率分别为6.5%、7.5%和18.6%（P<0.01）。一年时，无事件生存率分别为15%、12%和20%（P=0.01）。三组的总生存率无显著差异。接受白细胞介素-2治疗的患者比接受干扰素α-2a治疗的患者治疗毒性更常见。对治疗的反应与转移至单个器官及接受联合治疗有关。对于有至少两个转移部位、肝转移以及原发性肿瘤诊断与转移出现之间间隔少于一年的患者，疾病快速进展的概率至少为70%。
细胞因子对少数转移性肾细胞癌患者有效。细胞因子联合使用获得的较高缓解率和较长无事件生存率必须与这种治疗的毒性相权衡。
