Negrier S, Maral J, Drevon M, Vinke J, Escudier B, Philip T
Centre Léon-Bérard, Lyon, France.
Cancer J Sci Am. 2000 Feb;6 Suppl 1:S93-8.
The median survival for patients with metastatic renal cell carcinoma (mRCC) is generally < 1 year. Immunotherapy with high-dose recombinant interleukin (IL)-2 has been reported to produce objective responses in approximately 15% of treated patients and is associated with durable complete responses and prolonged survival in responding patients. The impact of IL-2 therapy on survival of metastatic renal cell carcinoma patients has begun to emerge, based on long-term follow-up data from large databases. Combinations of IL-2 and interferon alfa (IFN-alpha) have also been intensively investigated in mRCC.
Between 1987 and 1990, 281 mRCC patients were treated with continuous infusion IL-2 in three European multinational, single-arm phase II trials. Long-term treatment outcomes for these patients were analyzed, and the results are presented here. The results of a large, randomized French cooperative group trial (the Cancer Renal Cytokine [CRECY] study) that enrolled 425 patients between 1991 and 1995 are also summarized. Patients on this trial were randomized to treatment with IL-2 alone, IFN-alpha alone, or the combination.
Among patients included in the 281-patient database, the objective response rate was 15%. Median survival was 10 months; 41% of patients were alive at 1 year, 22% were alive at 2 years, and 8% were alive at 5 years. Among patients with a complete or partial response, 60% and 18% were alive at 5 years, respectively. No clinical factors were predictive for response or survival; however, no patient with a high endogenous IL-6 level at diagnosis responded to IL-2 therapy. The CRECY trial demonstrated that the combination of IL-2 and IFN-alpha induced a significantly higher response rate (P < 0.01) and significantly improved 1-year event-free survival (P = 0.01) compared with either agent alone, but overall survival was not significantly different between the three treatment groups.
The European experience suggests that the 5-year survival rate for metastatic renal cell carcinoma patients treated with high-dose continuous infusion IL-2 therapy is approximately 8% and that the majority of the therapeutic benefit is restricted to patients achieving a complete response. Therefore, given the toxicity, candidates for IL-2 therapy should be carefully selected. The combination of IL-2 and IFN-alpha does not appear to provide additional survival benefit. Efforts to further improve therapeutic outcome for patients with metastatic renal cell carcinoma should focus on understanding the underlying mechanisms of cytokine-induced tumor regression.
转移性肾细胞癌（mRCC）患者的中位生存期通常<1年。据报道，高剂量重组白细胞介素（IL）-2免疫疗法在约15%的接受治疗的患者中产生客观反应，并与持久的完全缓解和反应患者的生存期延长相关。基于大型数据库的长期随访数据，IL-2疗法对转移性肾细胞癌患者生存期的影响已开始显现。IL-2与干扰素α（IFN-α）的联合应用也在mRCC中得到了深入研究。
1987年至1990年期间，在三项欧洲多国单臂II期试验中，281例mRCC患者接受了持续输注IL-2治疗。分析了这些患者的长期治疗结果，并在此展示结果。还总结了1991年至1995年期间纳入425例患者的一项大型随机法国合作组试验（癌症肾细胞因子[CRECY]研究）的结果。该试验的患者被随机分配接受单独的IL-2治疗、单独的IFN-α治疗或联合治疗。
在纳入281例患者的数据库中，客观缓解率为15%。中位生存期为10个月；41%的患者在1年时存活，22%的患者在2年时存活，8%的患者在5年时存活。在完全缓解或部分缓解的患者中，5年时存活的分别为60%和18%。没有临床因素可预测反应或生存；然而，诊断时内源性IL-6水平高的患者对IL-2治疗均无反应。CRECY试验表明，与单独使用任何一种药物相比，IL-2与IFN-α联合使用诱导的缓解率显著更高（P<0.01），并显著改善了1年无事件生存期（P = 0.01），但三个治疗组之间的总生存期无显著差异。
欧洲的经验表明，接受高剂量持续输注IL-2治疗的转移性肾细胞癌患者的5年生存率约为8%，且大部分治疗益处仅限于实现完全缓解的患者。因此，鉴于毒性，应仔细选择IL-2治疗的候选者。IL-2与IFN-α联合使用似乎并未提供额外的生存益处。进一步改善转移性肾细胞癌患者治疗结果的努力应集中在了解细胞因子诱导肿瘤消退的潜在机制上。
