Effects of bacterially synthesized recombinant human granulocyte-macrophage colony-stimulating factor in patients with advanced malignancy.
Effects of bacterially synthesized recombinant human granulocyte-macrophage colony-stimulating factor in patients with advanced malignancy.
复制标题
细菌合成的重组人粒细胞-巨噬细胞集落刺激因子对晚期恶性肿瘤患者的影响。
DOI：
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发表时间：
1989
影响因子：
39.2
通讯作者：
G. Morstyn
中科院分区：
文献类型：
--
作者：
G. Lieschke;D. Maher;J. Cebon;M. O'Connor;Michael D. Green;W. Sheridan;A. Boyd;M. Rallings;E. Bonnem;D. Metcalf;A. Burgess;K. McGrath;R. Fox;G. Morstyn
学习目标
旨在确定皮下注射细菌合成的重组人粒细胞-巨噬细胞集落刺激因子 (rhGM-CSF) 的临床和血液学效应。
设计
单臂非随机剂量递增研究。
患者
21 名未接受同步骨髓抑制治疗的晚期恶性肿瘤患者。
干预措施
每天一次，以 0.3 至 30 微克/公斤体重的剂量，对 2 至 4 名患者进行皮下注射，连续 10 天。一些患者在 10 天不治疗间隔后接受第二个 10 天的每日 rhGM-CSF 治疗，然后隔日治疗。经常监测临床状态和血液学值。
测量和主要结果
所有剂量的 rhGM-CSF 均导致循环中性粒细胞、嗜酸性粒细胞和单核细胞立即短暂下降 84% 至 99%。持续每日给药导致白细胞增加高达 10 倍，循环中性粒细胞、嗜酸性粒细胞、单核细胞和淋巴细胞数量增加。在 3 至 15 微克/公斤·天的剂量范围内，中性粒细胞的增加似乎出现了一个平台期。骨髓抽吸物显示早幼粒细胞和中粒细胞比例增加。隔日注射 15 微克/公斤可维持白细胞增多。在剂量高达 15 微克/公斤·天时，rhGM-CSF 的耐受性良好，但副作用包括骨痛、肌痛、皮疹和肝功能障碍。当剂量超过 15 微克/千克·天时，心包炎是一种剂量限制性毒性。一名患者的特发性血小板减少性紫癜被 rhGM-CSF 重新激活。
结论
细菌合成的 rhGM-CSF 在 3 至 15 微克/kg.d 的剂量范围内诱导白细胞增多。这些剂量适合 II 期研究。
STUDY OBJECTIVE
To define the clinical and hematologic effects of subcutaneously administered bacterially synthesized recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF).
DESIGN
Single arm nonrandomized dose escalation study.
PATIENTS
Twenty-one patients with advanced malignancy who were not receiving concurrent myelosuppressive therapy.
INTERVENTIONS
Subcutaneous administration of rhGM-CSF by once-daily injection to groups of two to four patients at doses of 0.3 to 30 micrograms/kg body weight.d for 10 consecutive days. Some patients received a second 10-day period of daily rhGM-CSF treatment after a 10-day nontreatment interval followed by alternate-day treatment. Clinical status and hematologic values were monitored frequently.
MEASUREMENTS AND MAIN RESULTS
All doses of rhGM-CSF caused an immediate transient fall of 84% to 99% in circulating neutrophils, eosinophils, and monocytes. Continued daily dosing caused a leukocytosis of up to 10-fold with increases in numbers of circulating neutrophils, eosinophils, monocytes, and lymphocytes. There appeared to be a plateau in the increase in neutrophils in the dose range 3 to 15 micrograms/kg.d. Marrow aspirates showed increased proportions of promyelocytes and myelocytes. Alternate-day injection of 15 micrograms/kg maintained a leukocytosis. At doses up to 15 micrograms/kg.d, rhGM-CSF was well tolerated but adverse effects included bone pains, myalgias, rashes, and liver dysfunction. At doses exceeding 15 micrograms/kg.d, pericarditis was a dose-limiting toxicity. Idiopathic thrombocytopenic purpura was reactivated by rhGM-CSF in one patient.
CONCLUSIONS
Bacterially synthesized rhGM-CSF induces a leukocytosis in the dose range of 3 to 15 micrograms/kg.d. These doses are appropriate for phase II studies.
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影响因子：
15.9
作者：
LOPEZ, AF;WILLIAMSON, DJ;VADAS, MA
通讯作者：
VADAS, MA
人粒细胞-单核细胞集落刺激因子和白细胞介素 3 通过肿瘤坏死因子依赖性机制刺激单核细胞的细胞毒性。
影响因子：
20.3
作者：
Cannistra,SA;Vellenga,E;Groshek,P;Rambaldi,A;Griffin,JD
通讯作者：
Griffin,JD
重组人粒细胞-巨噬细胞集落刺激因子的体外生物学特性。
影响因子：
20.3
作者：
Metcalf,D;Begley,CG;Johnson,GR;Nicola,NA;Vadas,MA;Lopez,AF;Williamson,DJ;Wong,GG;Clark,SC;Wang,EA
通讯作者：
Wang,EA
影响因子：
158.5
作者：
GABRILOVE, JL;JAKUBOWSKI, A;SOUZA, L
通讯作者：
SOUZA, L
影响因子：
158.5
作者：
BRANDT, SJ;PETERS, WP;OETTE, DH
通讯作者：
OETTE, DH