Olencki Thomas, Malhi Sareena, Mekhail Tarek, Dreicer Robert, Elson Paul, Wood Laura, Bukowski Ronald M
Division of Hematology/Oncology, Department of Internal Medicine, Ohio State University, Columbus, Ohio 43210, USA.
Invest New Drugs. 2006 Jul;24(4):321-6. doi: 10.1007/s10637-005-5211-z.
The treatment of advanced renal cell cancer remains unsatisfactory, therefore new combination regimens such as thalidomide and IL-2 are of interest. A phase I trial of SC IL-2 and oral thalidomide was performed to identify the toxicity, maximum tolerated dose (MTD) and preliminary clinical activity of this regimen.
33 patients with advanced/metastatic RCC were enrolled. An established 8-week outpatient schedule of subcutaneously administered IL-2 in escalating doses, days 1-5, for 6 weeks with a 2 week rest was utilized with daily oral thalidomide. Cohorts of 4-6 patients were treated at 4 dose levels.
Toxicity was moderate to severe and related to dose level. All patients developed fever, chills and fatigue. 29/33 patients developed < or = Grade 2 desquamation of hands and feet and/or rash. Dose limiting toxicity (DLT) included Grade 3 neutropenia and pulmonary embolus. The maximum tolerated dose (MTD) of IL-2 and thalidomide was 9.0 MIU/m2 s.c. days 1-5, weeks 1 to 6 and 100 mg p.o. daily, respectively. A median of 2 cycles of therapy was administered (range 1-9). 2/33 patients responded (1 CR--prior IL-2 therapy, 1 PR--no prior therapy) with an overall response of 6% (95% CI, 1-20%). One minimal response was converted to a surgical CR (remains disease free at 24 + months).
Outpatient administration of IL-2 and thalidomide is possible with acceptable toxicity. Further evaluation of this regimen is underway.
晚期肾细胞癌的治疗仍不尽人意，因此诸如沙利度胺和白细胞介素-2（IL-2）的新联合方案备受关注。开展了一项皮下注射IL-2与口服沙利度胺的I期试验，以确定该方案的毒性、最大耐受剂量（MTD）及初步临床活性。
纳入33例晚期/转移性肾细胞癌患者。采用既定的为期8周的门诊方案，皮下注射递增剂量的IL-2，第1 - 5天给药，共6周，休息2周，同时每日口服沙利度胺。每组4 - 6例患者，在4个剂量水平进行治疗。
毒性为中度至重度，与剂量水平相关。所有患者均出现发热、寒战和疲劳。29/33例患者出现≤2级手足脱屑和/或皮疹。剂量限制性毒性（DLT）包括3级中性粒细胞减少和肺栓塞。IL-2和沙利度胺的最大耐受剂量分别为9.0 MIU/m²皮下注射，第1 - 5天，第1至6周，以及每日口服100 mg。中位给予2个周期治疗（范围1 - 9）。2/33例患者有反应（1例完全缓解[CR]——既往接受过IL-2治疗，1例部分缓解[PR]——既往未接受过治疗），总缓解率为6%（95%可信区间，1 - 20%）。1例微小反应转化为手术CR（24 +个月无疾病）。
门诊给予IL-2和沙利度胺可行，毒性可接受。该方案的进一步评估正在进行中。
