Nasr S, McKolanis J, Pais R, Findley H, Hnath R, Waldrep K, Ragab A H
Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia 30322.
Cancer. 1989 Aug 15;64(4):783-8. doi: 10.1002/1097-0142(19890815)64:4<783::aid-cncr2820640402>3.0.co;2-f.
The authors performed a Phase I study to assess the toxicity and hematologic effect of recombinant human interleukin-2 (rIL-2) in seven children with advanced malignancies. The rIL-2 was given as a bolus injection of 1 or 3 X 10(6) U/m2/dose three times a week (Monday, Wednesday, and Friday) for 3 weeks. No life-threatening toxicity occurred with the dose of 1 X 10(6) U/m2 of rIL-2. At a dose of 3 X 10(6) U/m2, therapy had to be terminated due to cardiovascular toxicity in two patients. Toxic effects at low-dose rIL-2 included fever, nausea, vomiting, and mild hypotension. High-dose rIL-2 toxicity included fluid retention, increased creatinine, oliguria, elevated liver enzymes, and significant hypotension. Immunologic studies showed that rIL-2 caused a drop in the number of circulating peripheral blood mononuclear cells, T-cells, and natural killer cells which returned to pretherapy levels or above by 24 to 48 hours. The rIL-2 exerted no growth or stimulatory activity on the leukemic cell population. To the authors' knowledge, this is the first report of a Phase I study of IL-2 therapy in children.
作者开展了一项I期研究，以评估重组人白细胞介素-2（rIL-2）对7名晚期恶性肿瘤患儿的毒性和血液学影响。rIL-2以1或3×10(6) U/m2/剂量的大剂量注射给药，每周三次（周一、周三和周五），共3周。1×10(6) U/m2剂量的rIL-2未出现危及生命的毒性。在3×10(6) U/m2的剂量下，两名患者因心血管毒性不得不终止治疗。低剂量rIL-2的毒性作用包括发热、恶心、呕吐和轻度低血压。高剂量rIL-2的毒性包括液体潴留、肌酐升高、少尿、肝酶升高和显著低血压。免疫学研究表明，rIL-2导致循环外周血单核细胞、T细胞和自然杀伤细胞数量下降，这些细胞数量在24至48小时内恢复到治疗前水平或以上。rIL-2对白血病细胞群体没有生长或刺激活性。据作者所知，这是关于儿童IL-2治疗I期研究的首次报告。
