PHASE-I STUDY OF THE ANTINEOVASCULARIZATION DRUG CM101

CM101 is a bacterial polysaccharide that induces neovascular inflammat ion 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 mu g)/kg to 5 units/kg. Serum was analyzed for anti-CM101 IgG and IgM weekly, Plasma levels of inflammatory cytokines, including tumor necrosis factor alpha, interl eukin 8, interleukin 10, MIP-1 alpha, and soluble E-selectin, were ana lyzed from -15 min to 12 h during each treatment. Dose-limiting toxici ties, including grade IV dyspnea and arrhythmia, were encountered at t he 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. Al l patients experienced marked time- and dose-dependent elevations in a ll cytokines studied. Three patients experienced tumor shrinkage. The results show that CM101 can be safely administered at doses that produ ce evidence for severe, and possibly tumor-specific, inflammation. Fur ther study is necessary to better characterize the mechanism of action and determine the optimal dose and schedule of this new agent.