Phase I study of the antineovascularization drug CM101

Russell F. DeVore, Carl G. Hellerqvist, Gail B. Wakefield, Barbara D. Wamil, Gary B. Thurman, Patricia A. Minton, Håkan W. Sundell, He Ping Yan, Clint E. Carter, Yue Fen Wang, Gerald E. York, Ming Hua Zhang, David H. Johnson

Research output: Contribution to journalArticle

43 Scopus citations

Abstract

CM101 is a bacterial polysaccharide that induces neovascular inflammation in malignant tumors. Fifteen patients with refractory malignancies received CM101 i.v. by a 15-min infusion every other day, three times in 1 week, at doses ranging from 1 unit (7.5 μg/kg to 5 units/kg. Serum was analyzed for anti-CM101 IgG and IgM weekly. Plasma levels of inflammatory cytokines, including tumor necrosis factor α, interleukin 8, interleukin 10, MIP-1α, and soluble E-selectin, were analyzed from -15 min to 12 h during each treatment. Dose-limiting toxicities, including grade IV dyspnea and arrhythmia, were encountered at the 5-unit/kg level. Toxicities occurred primarily within the first 12 h after therapy and included mild-to-moderate fever and chills, nausea, cough, headache, facial flushing, dyspnea, myalgias, and acute tumor-related pain. No patient developed detectable antibodies to CM101. All patients experienced marked time- and dose-dependent elevations in all cytokines studied. Three patients experienced tumor shrinkage. The results show that CM101 can be safely administered at doses that produce evidence for severe, and possibly tumor-specific, inflammation. Further study is necessary to better characterize the mechanism of action and determine the optimal dose and schedule of this new agent.

Original languageEnglish (US)
Pages (from-to)365-372
Number of pages8
JournalClinical Cancer Research
Volume3
Issue number3
Publication statusPublished - 1997

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ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

DeVore, R. F., Hellerqvist, C. G., Wakefield, G. B., Wamil, B. D., Thurman, G. B., Minton, P. A., ... Johnson, D. H. (1997). Phase I study of the antineovascularization drug CM101. Clinical Cancer Research, 3(3), 365-372.