Gerena-Lewis Margie, Crawford Jeffrey, Bonomi Philip, Maddox Ann Marie, Hainsworth John, McCune David E, Shukla Rakesh, Zeigler Haoyue, Hurtubise Paul, Chowdhury Tracy R, Fletcher Brandon, Dyehouse Karyn, Ghalie Richard, Jazieh Abdul R
University of Cincinnati, OH, USA.
Am J Clin Oncol. 2009 Jun;32(3):269-73. doi: 10.1097/COC.0b013e318187dd40.
Denileukin diftitox, a chimeric protein, uses the cytocidal properties of diphtheria toxin to cells expressing interleukin-2 receptors. The aim of this study was to evaluate the efficacy and safety of denileukin diftitox in the treatment of advanced relapsed nonsmall cell lung cancer (NSCLC).
Multicenter phase II trial in patients with NSCLC with Eastern Cooperative Oncology Group PS 0-2, stage IIIB/IV at diagnosis, who had failed at least 1 previous chemotherapy regimen. Denileukin diftitox was infused at 18 microg/kg/d x 5 days, every 21 days for 6 cycles.
For the 41 patients enrolled, the median age was 56 years (range, 21-80), 25 were men, and the median number of previous chemotherapy regimens was 2 (range, 1-5). The median number of treatment cycles was 2 (range, 1-6). By RECIST criteria, 18 (44%) had stable disease, 10 (24%) progressive disease, and 13 (32%) were not evaluable for response as they received less than 2 treatment cycles. The median time to disease progression was 1.8 months [range, 0.3-11.3; 95% confidence interval (CI) 1.3-2.6]. Median survival was 5.8 months (range, 0.3-33.6; 95% CI 3.4-11.4). The median follow-up time was 16.1 month. One death from myocarditis verified at autopsy was attributed to treatment. One grade 4 toxicity (vascular leak syndrome) was encountered, and 18 grade 3 toxicities, primarily gastro-intestinal, vascular leak syndrome, and constitutional symptoms.
Denileukin diftitox at current dose schedule has limited activity in patients with previously treated NSCLC, manifested by disease control without impact on survival.
地尼白介素-妥昔单抗是一种嵌合蛋白，利用白喉毒素对表达白细胞介素-2受体的细胞的杀伤特性。本研究的目的是评估地尼白介素-妥昔单抗治疗晚期复发非小细胞肺癌（NSCLC）的疗效和安全性。
对东部肿瘤协作组体能状态评分为0 - 2、诊断为ⅢB/Ⅳ期、既往至少一种化疗方案治疗失败的NSCLC患者进行多中心Ⅱ期试验。地尼白介素-妥昔单抗以18μg/kg/d的剂量输注5天，每21天为一个周期，共6个周期。
入组的41例患者中，中位年龄为56岁（范围21 - 80岁），男性25例，既往化疗方案的中位次数为2次（范围1 - 5次）。治疗周期的中位次数为2次（范围1 - 6次）。根据RECIST标准，18例（44%）疾病稳定，10例（24%）疾病进展，13例（32%）因接受的治疗周期少于2个而无法评估疗效。疾病进展的中位时间为1.8个月[范围0.3 - 11.3；95%置信区间（CI）1.3 - 2.6]。中位生存期为5.8个月（范围0.3 - 33.6；95%CI 3.4 - 11.4）。中位随访时间为16.1个月。尸检证实1例死于心肌炎，归因于治疗。出现1例4级毒性反应（血管渗漏综合征），18例3级毒性反应，主要为胃肠道反应、血管渗漏综合征和全身症状。
按照当前剂量方案，地尼白介素-妥昔单抗对既往接受治疗的NSCLC患者活性有限，表现为疾病得到控制但对生存无影响。
