Furman W L, Luo X, Fairclough D, Garrison L, Marina N, Pratt C B, Bleyer A, Meyer W H
Department of Hematology-Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105-2794, USA.
Med Pediatr Oncol. 1997 Jun;28(6):444-50. doi: 10.1002/(sici)1096-911x(199706)28:6<444::aid-mpo10>3.0.co;2-9.
Interleukin-1 alpha (IL-1 alpha) is myeloprotective in a variety of animal models of cancer chemotherapy and is similarly beneficial in adults treated with carboplatin, 5-fluorouracil, and after autologous bone marrow transplantation. There are no trials of this agent in children. Our purpose was to determine the toxicity and maximum tolerated dose (MTD) of recombinant human interleukin-1 alpha (rhuIL-1 alpha) in children with solid tumors receiving intensive cancer chemotherapy and to evaluate its myelo-protective effects. Cohorts of patients received rhuIL-1 alpha in doses of 0.1-10 micrograms/m2 for 4 days by subcutaneous injection prior to ICF chemotherapy (ifosfamide, 2 g/m2/day x 3, carboplatin targeted to an area under the curve of 8 mg/ml x min on day 1, and etoposide, 100 mg/m2 daily for 3 days). Patients were randomized to receive rhuIL-1 alpha before either the first or second course of therapy. After the MTD of rhuIL-1 alpha was determined an additional group of patients received rhuIL-1 alpha at the dose immediately following ICE chemotherapy. The dose-limiting toxicities of rhuIL-1 alpha in the 27 children tested comprised systemic symptoms of fever, chills, headache, and hypotension. The MTD was 3 micrograms/m2/day. There were no differences in chemotherapy-induced hematologic toxicity with increasing doses of rhuIL-1 alpha or in comparisons before or after ICE chemotherapy. Although rhuIL-1 alpha can be given safely to children receiving myelosuppressive chemotherapy, clinical usefulness would mandate a significant hematopoietic benefit in view of the trouble some side effects identified. We saw no evidence of a hematoprotective effect.
白细胞介素 -1α（IL -1α）在多种癌症化疗动物模型中具有骨髓保护作用，对接受卡铂、5 -氟尿嘧啶治疗的成人以及自体骨髓移植后的成人同样有益。目前尚无该药物在儿童中的试验。我们的目的是确定重组人白细胞介素 -1α（rhuIL -1α）在接受强化癌症化疗的实体瘤儿童中的毒性和最大耐受剂量（MTD），并评估其骨髓保护作用。在进行ICF化疗（异环磷酰胺，2 g/m²/天×3天，第1天卡铂靶向曲线下面积为8 mg/ml×分钟，依托泊苷，100 mg/m²/天×3天）之前，患者队列通过皮下注射接受剂量为0.1 - 10微克/平方米的rhuIL -1α，持续4天。患者被随机分配在第一疗程或第二疗程之前接受rhuIL -1α。确定rhuIL -1α的MTD后，另一组患者在ICE化疗后立即接受rhuIL -1α。在接受测试的27名儿童中，rhuIL -1α的剂量限制性毒性包括发热、寒战、头痛和低血压等全身症状。MTD为3微克/平方米/天。随着rhuIL -1α剂量增加，化疗引起的血液学毒性与ICE化疗前后的比较均无差异。尽管rhuIL -1α可以安全地给予接受骨髓抑制化疗的儿童，但鉴于已发现的一些麻烦的副作用，其临床实用性需要有显著的造血益处。我们没有发现骨髓保护作用的证据。
