Guleria A S, Yang J C, Topalian S L, Weber J S, Parkinson D R, MacFarlane M P, White R L, Steinberg S M, White D E, Einhorn J H
Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
J Clin Oncol. 1994 Dec;12(12):2714-22. doi: 10.1200/JCO.1994.12.12.2714.
To describe the incidence and management of renal dysfunction associated with the use of high-dose interleukin-2 (IL-2) (as is currently approved) in the treatment of cancer patients.
One hundred ninety-nine consecutive patients with metastatic renal carcinoma or melanoma were treated with intravenous bolus infusions of IL-2 alone (720,000 IU/kg) every 8 hours.
Patients received 310 courses (589 cycles) of therapy and most experienced oliguria, hypotension, and weight gain; 13% of cycles were discontinued due to increased serum creatinine levels. Creatinine values (mean pretherapy, 1.2 mg/dL) increased during therapy and peaked (mean, 2.7 mg/dL) approximately 1 day after discontinuation of the second cycle of IL-2. Off therapy, toxicities reversed promptly and creatinine values returned to baseline. Higher peak creatinine values occurred in patients with renal carcinoma (v melanoma), older patients, males (v females), and those who had undergone prior nephrectomy. These same patient subsets received fewer doses of IL-2, but clinical responses were not associated with creatinine values or number of IL-2 doses administered. Urinalyses showed the appearance of protein, bilirubin, RBCs, WBCs, and granular casts during therapy, which cleared completely on follow-up evaluation.
High-dose IL-2 can be safely administered to cancer patients. The associated renal dysfunction is transient and without evidence of intrinsic long-term renal damage. Practical guidelines for patient management have been identified.
描述在癌症患者治疗中使用高剂量白细胞介素-2（IL-2）（如当前获批使用的）所伴随的肾功能不全的发生率及处理方法。
199例连续的转移性肾癌或黑色素瘤患者接受每8小时静脉推注一次IL-2（720,000 IU/kg）的单独治疗。
患者共接受了310个疗程（589个周期）的治疗，大多数患者出现少尿、低血压和体重增加；13%的周期因血清肌酐水平升高而中断。肌酐值（治疗前平均为1.2 mg/dL）在治疗期间升高，并在停用第二个周期的IL-2后约1天达到峰值（平均为2.7 mg/dL）。停止治疗后，毒性反应迅速逆转，肌酐值恢复至基线水平。肾癌（对比黑色素瘤）患者、老年患者、男性（对比女性）以及曾接受过肾切除术的患者出现的肌酐峰值更高。这些相同的患者亚组接受的IL-2剂量较少，但临床反应与肌酐值或给予的IL-2剂量数量无关。尿液分析显示治疗期间出现蛋白质、胆红素、红细胞、白细胞和颗粒管型，在随访评估时完全清除。
高剂量IL-2可安全地给予癌症患者。相关的肾功能不全是短暂的，且无内在长期肾损害的证据。已确定了患者管理的实用指南。
