Margolin K A, Doroshow J H, Akman S A, Leong L A, Morgan R J, Raschko J, Somlo G, Mills B, Goldberg D, Sniecinski I
Department of Medical Oncology, City of Hope National Medical Center, Duarte, CA 91010-0269.
J Immunother (1991). 1992 Jan;11(1):50-5. doi: 10.1097/00002371-199201000-00006.
Interleukin-2 (IL-2) and gamma interferon (gamma-IFN) may be synergistic in inducing cell-mediated antitumor cytotoxicity. In order to determine the dose-limiting toxicities and define a maximum tolerated dose of these two agents in combination, we performed a Phase I clinical trial of intravenous IL-2 plus intramuscular gamma-IFN. Patients received both agents on a thrice-weekly schedule consisting of 4 weeks of treatment followed by 2 weeks of rest. Twenty-five patients were treated and received gamma-IFN doses between 0.05-0.25 mg/m2 (1-4 x 10(6) U/m2) with IL-2 doses from 0.33 mg/m2 to 2.33 mg/m2 (6-42 x 10(6) IU/m2). Two patients had partial responses of melanoma and adenocarcinoma of the lung lasting greater than 11 and 8 months, respectively. The toxicities of the combination were those expected from each agent, with no unusual effects, no irreversible organ toxicities, and no patient deaths. The doses recommended for outpatient administration on this schedule are IL-2, 2.0 mg/m2 plus gamma-IFN, 0.25 mg/m2, a dose combination that is unassociated with significant organ toxicity.
白细胞介素-2（IL-2）和γ干扰素（γ-IFN）在诱导细胞介导的抗肿瘤细胞毒性方面可能具有协同作用。为了确定这两种药物联合使用时的剂量限制性毒性并确定最大耐受剂量，我们进行了一项静脉注射IL-2加肌肉注射γ-IFN的I期临床试验。患者按每周三次的方案接受两种药物治疗，为期4周，随后休息2周。25名患者接受了治疗，γ-IFN剂量为0.05 - 0.25mg/m²（1 - 4×10⁶U/m²），IL-2剂量为0.33mg/m²至2.33mg/m²（6 - 42×10⁶IU/m²）。两名患者分别出现了黑色素瘤和肺腺癌的部分缓解，持续时间分别超过11个月和8个月。联合用药的毒性是每种药物预期的毒性，没有异常效应，没有不可逆的器官毒性，也没有患者死亡。按照该方案推荐的门诊给药剂量为IL-2 2.0mg/m²加γ-IFN 0.25mg/m²，这种剂量组合与显著的器官毒性无关。
