Phase I trial of recombinant macrophage colony-stimulating factor by rapid intravenous infusion in patients with cancer.

B G Redman, L Flaherty, T H Chou, M Kraut, S Martino, M Simon, M Valdivieso, E Groves
{"title":"Phase I trial of recombinant macrophage colony-stimulating factor by rapid intravenous infusion in patients with cancer.","authors":"B G Redman, L Flaherty, T H Chou, M Kraut, S Martino, M Simon, M Valdivieso, E Groves","doi":"10.1097/00002371-199207000-00006","DOIUrl":null,"url":null,"abstract":"<p><p>Fourteen patients were entered into a phase I dose-escalation trial of macrophage colony-stimulating factor (M-CSF). M-CSF was administered to inpatients by rapid 15 min i.v. infusion every 8 h x 5 days, repeated after a 9-day rest. Dose levels evaluated were 20, 40, 80, 330, and 1,100 micrograms/m2. Monitoring of patients every 4 h included vital signs, daily complete blood count (CBC), and serum chemistries (SGOT, creatinine, and bilirubin) while receiving M-CSF. No clinical or laboratory evidence of toxicity was seen. The average serum t1/2 varied with dose level. At 330 and 1,100 micrograms/m2, the serum t1/2 was 25 and 84 min, respectively, implying a saturable mechanism of clearance. After 5 days of treatment, the t1/2 decreased by twofold, consistent with enhancement of the saturable mechanism. Monocyte cytotoxicity against the A375 melanoma cell line was evaluated pretreatment and day 5 of each cycle. No consistent enhancement of monocyte cytotoxicity was seen. No effect on peripheral blood monocyte number was seen until the 1,100 micrograms/m2 dose level. At this dose level, the mean monocyte number on day 5 was increased compared to baseline (1,300 mm3 vs. 300/mm3). Clinical activity was seen in two patients with previously progressive leiomyosarcoma metastatic to the liver. A partial response (PR) lasting 7 months occurred at the 330 micrograms/m2 dose level while a patient treated at 1,100 micrograms/m2 has had stable disease for 20+ months. The maximum tolerated dose (MTD) of M-CSF was not determined. Based on clinical responses, a phase II trial is warranted in patients with metastatic soft tissue sarcoma.</p>","PeriodicalId":77209,"journal":{"name":"Journal of immunotherapy : official journal of the Society for Biological Therapy","volume":"12 1","pages":"50-4"},"PeriodicalIF":0.0000,"publicationDate":"1992-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1097/00002371-199207000-00006","citationCount":"27","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of immunotherapy : official journal of the Society for Biological Therapy","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1097/00002371-199207000-00006","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 27

Abstract

Fourteen patients were entered into a phase I dose-escalation trial of macrophage colony-stimulating factor (M-CSF). M-CSF was administered to inpatients by rapid 15 min i.v. infusion every 8 h x 5 days, repeated after a 9-day rest. Dose levels evaluated were 20, 40, 80, 330, and 1,100 micrograms/m2. Monitoring of patients every 4 h included vital signs, daily complete blood count (CBC), and serum chemistries (SGOT, creatinine, and bilirubin) while receiving M-CSF. No clinical or laboratory evidence of toxicity was seen. The average serum t1/2 varied with dose level. At 330 and 1,100 micrograms/m2, the serum t1/2 was 25 and 84 min, respectively, implying a saturable mechanism of clearance. After 5 days of treatment, the t1/2 decreased by twofold, consistent with enhancement of the saturable mechanism. Monocyte cytotoxicity against the A375 melanoma cell line was evaluated pretreatment and day 5 of each cycle. No consistent enhancement of monocyte cytotoxicity was seen. No effect on peripheral blood monocyte number was seen until the 1,100 micrograms/m2 dose level. At this dose level, the mean monocyte number on day 5 was increased compared to baseline (1,300 mm3 vs. 300/mm3). Clinical activity was seen in two patients with previously progressive leiomyosarcoma metastatic to the liver. A partial response (PR) lasting 7 months occurred at the 330 micrograms/m2 dose level while a patient treated at 1,100 micrograms/m2 has had stable disease for 20+ months. The maximum tolerated dose (MTD) of M-CSF was not determined. Based on clinical responses, a phase II trial is warranted in patients with metastatic soft tissue sarcoma.

通过快速静脉注射重组巨噬细胞集落刺激因子治疗癌症患者的 I 期试验。
14名患者参加了巨噬细胞集落刺激因子(M-CSF)的I期剂量递增试验。M-CSF每8小时静脉快速输注15分钟,连续输注5天,休息9天后重复输注。评估的剂量水平为 20、40、80、330 和 1,100 微克/平方米。在接受 M-CSF 治疗期间,每 4 小时对患者进行一次监测,包括生命体征、每日全血细胞计数(CBC)和血清化学指标(SGOT、肌酐和胆红素)。未发现任何临床或实验室毒性证据。平均血清 t1/2 随剂量水平而变化。在 330 微克/平方米和 1,100 微克/平方米剂量下,血清 t1/2 分别为 25 分钟和 84 分钟,这意味着清除机制达到饱和。治疗 5 天后,t1/2 下降了两倍,这与饱和机制的增强相一致。单核细胞对 A375 黑色素瘤细胞系的细胞毒性在治疗前和每个周期的第 5 天进行了评估。未发现单核细胞细胞毒性持续增强。在 1100 微克/平方米的剂量水平之前,外周血单核细胞数量没有受到影响。在这一剂量水平,第 5 天的平均单核细胞数量比基线有所增加(1,300 立方毫米对 300/立方毫米)。两名曾患进展性肝转移细肌瘤的患者出现了临床活性。330微克/平方米剂量水平的患者出现了持续7个月的部分应答(PR),而1100微克/平方米剂量水平的患者病情稳定了20多个月。M-CSF 的最大耐受剂量 (MTD) 尚未确定。根据临床反应,有必要对转移性软组织肉瘤患者进行 II 期试验。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
自引率
0.00%
发文量
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信