Witte R S, Leong T, Ernstoff M S, Krigel R L, Oken M M, Harris J, Tormey D C, Trump D L
Gundersen Clinic, Ltd., La Crosse, WI, USA.
Invest New Drugs. 1995;13(3):241-7. doi: 10.1007/BF00873807.
Biologic response modifiers have activity in renal cell carcinoma. The combination of interleukin-2 (IL-2) and beta-interferon (B-IFN) is synergistic in vitro. This trial was initiated to determine the efficacy of IL-2 alone and with B-IFN in advanced RCC.
Ambulatory patients with advanced RCC were randomly allocated to either IL-2 6 x 10(6) units/M2 intravenously (IV) three days a week for four weeks or IL-2 5 x 10(6) units/M2 IV plus B-IFN 6 x 10(6) units/M2 IV three days a week for 4 weeks. This induction phase was followed by a maintenance phase of the same drugs and doses administered for two weeks out of every four.
84 patients were entered onto this phase II trial with 75 considered eligible for response and survival. Toxicity is reported for the 81 patients on whom data was received, irrespective of eligibility. The overall response rate (RR) was 9.3% (7/75). Of the 3 responses in the IL-2 arm (RR = 8.3%), one was a complete response. 4 patients in the IL-2 + B-IFN arm (RR = 10.3%) achieved a partial response. Median survival was estimated to be 8.4 months for patients given IL-2 and 8.0 months for patients given the IL-2 and B-IFN combination. Multivariate analysis of survival data identified initial performance status, metastases of > 1 site, and weight loss as being important prognostic factors for survival. There were 2 lethal and 3 life threatening toxicities with the IL-2 treatment. While there were no lethal toxicities on the combination arm, there were 4 life threatening toxicities.
The results of this study indicate that further investigation of IL-2 with or without B-IFN at this dose and schedule as treatments for renal cell carcinoma is probably not warranted.
生物反应调节剂对肾细胞癌有活性。白细胞介素-2（IL-2）和β-干扰素（B-IFN）联合在体外具有协同作用。启动该试验以确定单独使用IL-2以及与B-IFN联合使用在晚期肾细胞癌中的疗效。
晚期肾细胞癌的门诊患者被随机分配至以下两组：一组接受IL-2 6×10⁶单位/平方米静脉注射，每周3天，共4周；另一组接受IL-2 5×10⁶单位/平方米静脉注射加B-IFN 6×10⁶单位/平方米静脉注射，每周3天，共4周。诱导期之后是维持期，每4周中有2周给予相同药物和剂量。
84例患者进入该II期试验，75例被认为符合反应和生存评估条件。报告了81例有数据患者的毒性情况，无论其是否符合条件。总缓解率（RR）为9.3%（7/75）。IL-2组的3例缓解（RR = 8.3%）中，1例为完全缓解。IL-2 + B-IFN组的4例患者（RR = 10.3%）达到部分缓解。接受IL-2治疗患者的中位生存期估计为8.4个月，接受IL-2和B-IFN联合治疗患者的中位生存期为8.0个月。生存数据的多因素分析确定初始体能状态、转移部位>1个以及体重减轻是生存的重要预后因素。IL-2治疗有2例致命和3例危及生命的毒性反应。联合治疗组虽无致命毒性反应，但有4例危及生命的毒性反应。
本研究结果表明，以该剂量和方案使用或不使用B-IFN的IL-2作为肾细胞癌治疗方法可能无需进一步研究。
