重组人源化白细胞介素2治疗转移性肾癌的临床研究

Clinical study on recombinant human interleukin-2 （Proleukin）in the treatment of metastatic renal cell carcinoma

目的观察重组人源化白细胞介素2皮下注射治疗转移性肾癌的疗效及安全性。方法入组转移性肾癌患者41例，经重组人源化白细胞介素2皮下注射治疗2～4个周期，每个周期共5周。第1个周期：9百万单位（MIU）、每12h1次、第1～5天；第2～4个周期：9MIU、每12h1次、第1～2天，9MIU、每天1次、第3～5天；停药1周后重复。2个周期后评价疗效，有效或稳定的患者继续2个周期治疗。结果意向治疗人群（ITT）集中，完全缓解（CR）0例，部分缓解（PR）7例（17．1％），病情稳定（SD）19例（46．3％），疾病进展（PD）15例（36．6％），总有效率为17．1％[95％可信区间（叫）为5．6％～28．6％]，疾病控制率为63．4％；中位疾病进展时间（下rP）为6个月，中位总生存时间（OS）为22．5个月，1年生存率为71．2％。符合方案人群（PP）集中，CR0例，PR7例（19．4％），SD16例（44．4％），PD13例（36．1％），总有效率为19．4％（95％ CI 为6．5％～32．3％），疾病控制率为63．9％；中位TTP为6个月，中位OS未达到，1年生存率为66．7％。随访显示，治疗获益能够改善患者的长期生存。患者的不良反应以轻中度为主，包括疲乏感（100％）和发热（82．9％）等，3级以上不良反应少见。结论重组人源化白细胞介素2治疗转移性肾癌在中国人中具有一定的疗效，且能延长患者的生存期，其不良反应大部分患者能够耐受。

Objective To evaluate the efficacy and safety of subcutaneous injection of recombinant human interleukin-2 （Proleukin） in the treatment of metastatic renal cell carcinoma （RCC）. Methods Forty- one patients with pathologically confirmed metastatic RCC after radical nephrectomy were enrolled into this study. Two or four consecutive cycles of subcutaneous injection of rhIL-2 were given, with each cycle duration of five weeks consisting of 4 weeks of treatment and one week of rest. The rhlL-2 was injected twice daily subcutaneously at a dose of 9 MIU on D1-D5 during week one, then 9 MIU twice daily on D1-D2 and followed by 9 MIU daily on D3-D5 during week 2-4. Patients were evaluated after the second cycle of treatment. If an objective response or stable disease was observed, the patient would receive another two cycles of treeatment. Results Of the 41 patients, the overall objective response rate was 17.1% （95% confidence interval, 5.6% to 28.6% ） with a complete response （CR） rate of 0.0% and partial response rate （PR）of 17.1%. However, nineteen patients （46.3%） still had a stable disease （SD）, and 15（36.6%） had progressed disease （PD）. The disease control rate was 63.4% and the median time to progression （mTTP） Was 6 months. The 1-year survival rate was 71.2% with a median overall survival （mOS） rate of 22.5 months. Among 36 PP population, the overall objective response rate was 19.4% （95% confidence interval, 6.5% to 32.3% ） with CR rate of 0.0% and PR rate of 19.4%. Sixteen patients（44.4% ） had stable disease, and 13 （36.1%） progressed disease. The disease control rate was 63.9%. The 1-year survival rate was 66.7% with a median time to progression of 6 months. The median overall survival （mOS） had not reached yet. The follow-up data showed that the long term survival of the patient who responsed to the IL-2 therapy can be prolonged. Severe toxicity （ ≥ grade Ⅲ ） was rarely observed. Grade Ⅰ or Ⅱ toxicities such as fatigue （100. 0% ） and fever （82. 9% ） were frequently observed but reversible. Conclusion Subcutaneous injection of recombinant human interleukin-2 may prolong the survival of patients with a metastatic renal cell carcinoma. This regimen is tolerable with rare severe toxicities.