Motzer R J, Rakhit A, Thompson J A, Nemunaitis J, Murphy B A, Ellerhorst J, Schwartz L H, Berg W J, Bukowski R M
Genitourinary Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
J Interferon Cytokine Res. 2001 Apr;21(4):257-63. doi: 10.1089/107999001750169934.
Recombinant human interleukin-12 (rHuIL-12) is a pleiotropic cytokine with anticancer activity against renal cell carcinoma (RCC) in preclinical models and in a phase I trial. A randomized phase II study of rHuIL-12 compared with interferon-alpha (IFN-alpha) evaluated clinical response for patients with previously untreated, advanced RCC. Patients were randomly assigned 2:1 to receive either rHuIL-12 or IFN-alpha2a. rHuIL-12 was administered by subcutaneous (s.c.) injection on days 1, 8, and 15 of each 28-day cycle. The dose of IL-12 was escalated during cycle 1 to a maintenance dose of 1.25 microg/kg. IFN was administered at 9 million units by s.c. injection three times per week. Serum concentrations of IL-12, IFN-gamma, IL-10, and neopterin were obtained in 10 patients treated with rHuIL-12 after the first full dose of 1.25 microg/kg given on day 15 (dose 3) of cycle 1 and again after multiple doses on day 15 (dose 6) of cycle 2. Thirty patients were treated with rHuIL-12, and 16 patients were treated with IFN-alpha. Two (7%) of 30 patients treated with rHuIL-12 achieved a partial response, and the trial was closed to accrual based on the low response proportion. IL-12 was absorbed rapidly after s.c. drug administration, with the peak serum concentration appearing at approximately 12 h in both cycles. Serum IL-12 concentrations remained stable on multiple dosing. Levels of IFN-gamma, IL-10, and neopterin increased with rHuIL-12 and were maintained in cycle 2. rHuIL-12 is a novel cytokine with unique pharmacologic and pharmacodynamic features under study for the treatment of malignancy and other medical conditions. The low response proportion associated with rHuIL-12 single-agent therapy against metastatic RCC was disappointing, given the preclinical data. Further study of rHuIL-12 for other medical conditions is underway. For RCC, the study of new cytokines is of the highest priority.
重组人白细胞介素-12（rHuIL-12）是一种多效性细胞因子，在临床前模型和一项I期试验中对肾细胞癌（RCC）具有抗癌活性。一项将rHuIL-12与α干扰素（IFN-α）进行比较的随机II期研究评估了先前未接受治疗的晚期RCC患者的临床反应。患者按2:1随机分组，分别接受rHuIL-12或IFN-α2a治疗。rHuIL-12在每个28天周期的第1、8和15天通过皮下（s.c.）注射给药。在第1周期中，IL-12的剂量逐步增加至维持剂量1.25μg/kg。IFN通过皮下注射，每周3次，每次900万单位给药。在第1周期第15天（第3剂）给予1.25μg/kg的首次全剂量后，对10例接受rHuIL-12治疗的患者进行血清IL-12、IFN-γ、IL-10和新蝶呤浓度检测，并在第2周期第15天（第6剂）多次给药后再次检测。30例患者接受rHuIL-12治疗，16例患者接受IFN-α治疗。接受rHuIL-12治疗的30例患者中有2例（7%）获得部分缓解，鉴于缓解率较低，该试验停止入组。皮下给药后，IL-12吸收迅速，两个周期的血清浓度峰值均出现在约12小时。多次给药后血清IL-12浓度保持稳定。rHuIL-12治疗后，IFN-γ、IL-10和新蝶呤水平升高，并在第2周期维持。rHuIL-12是一种新型细胞因子，具有独特的药理和药效学特性，正在研究用于治疗恶性肿瘤和其他疾病。鉴于临床前数据，rHuIL-12单药治疗转移性RCC的缓解率较低，令人失望。针对其他疾病的rHuIL-12进一步研究正在进行中。对于RCC，新型细胞因子的研究具有最高优先级。
