Adis International Limited, Auckland, New Zealand.
BioDrugs. 1997 Apr;7(4):285-317. doi: 10.2165/00063030-199707040-00005.
Aldesleukin (recombinant interleukin-2), like endogenous interleukin-2 (IL-2), has a variety of immunomodulatory properties. It is currently approved for intravenous use in patients with renal cell carcinoma, in whom it appears to have an indirect antitumour effect mediated by increased activity of the host's immune system. A large number of clinical trials (typically noncomparative) have established the efficacy of aldesleukin monotherapy in patients with renal cell carcinoma. Response rates of 13 to 20% achieved after intravenous administration and 18 to 31% after subcutaneous administration are greater than those previously reported ( approximately 10%) for other chemo- and immunotherapeutic agents. Furthermore, many patients who were previously refractory to treatment have achieved stable disease status or better after aldesleukin therapy. Median survival times of at least 37 months have been achieved, and perhaps more encouraging is an isolated report of a 5-year actuarial survival rate of 23%. Bolus intravenous administration of aldesleukin was associated with frequent, and occasionally life-threatening, adverse events. Hypotension and renal, pulmonary and cardiac complications were primarily manifestations of increased vascular permeability. Symptoms were generally manageable with treatment interruption and standard pharmaceutical and/or clinical intervention, although some treatment-related deaths were reported. The severity of adverse events was reduced with continuous infusion of the agent and more substantially so when aldesleukin was administered subcutaneously. In conclusion, despite a lack of comparative and phase III trials, aldesleukin therapy appears to result in a slightly better response rate than those previously reported with other antineoplastic therapies in this difficult-to-treat patient population. Retrospective data indicate that survival duration may be moderately increased by aldesleukin, but further prospective comparative data are required before this may be proven. In view of the poor prognosis associated with renal cell carcinoma, efficacy data from clinical trials evaluating aldesleukin, together with the potential for reducing adverse events by changing its route of administration, suggest the drug may be a worthwhile therapy for patients with this disease.
白细胞介素-2（IL-2）是一种具有多种免疫调节特性的细胞因子。目前，它被批准用于静脉注射治疗肾细胞癌患者，其抗肿瘤作用可能是通过增强宿主免疫系统的活性而间接发挥的。大量临床试验（通常是非对照性的）已证实白细胞介素-2 单独治疗肾细胞癌的疗效。静脉注射后缓解率为 13%20%，皮下注射后缓解率为 18%31%，高于以前报道的其他化疗和免疫治疗药物（约 10%）。此外，许多先前对治疗有抵抗的患者在接受白细胞介素-2 治疗后病情稳定或改善。中位生存时间至少为 37 个月，更令人鼓舞的是有 1 例患者的 5 年实际生存率为 23%。白细胞介素-2 静脉推注常引起频繁且有时危及生命的不良反应。低血压、肾、肺和心脏并发症主要表现为血管通透性增加。一般通过中断治疗和标准药物及/或临床干预可控制症状，但有报道称一些治疗相关死亡。连续输注该药物可降低不良反应的严重程度，而皮下注射则更为显著。总之，尽管缺乏对照和 III 期临床试验，白细胞介素-2 治疗似乎比以前报道的其他抗肿瘤疗法在这一治疗困难的患者群体中具有略高的缓解率。回顾性数据表明，白细胞介素-2 可能会适度延长生存时间，但需要进一步的前瞻性对照数据来证明这一点。鉴于肾细胞癌的预后较差，评估白细胞介素-2 的临床试验的疗效数据，加上通过改变给药途径降低不良反应的可能性，提示该药可能是治疗这种疾病的一种有价值的治疗方法。
