title: Phase I study of the antineovascularization drug CM101.
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 microgram)/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, interleukin 8, interleukin 10, MIP-1alpha, 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.
authors.affiliation: Departments of Medicine, Biochemistry, Pediatrics, and Biology, Vanderbilt University, Nashville, Tennessee 37232, USA.
authors.forename: R F
authors.initials: RF
authors.lastname: DeVore
authors.forename: C G
authors.initials: CG
authors.lastname: Hellerqvist
authors.forename: G B
authors.initials: GB
authors.lastname: Wakefield
authors.forename: B D
authors.initials: BD
authors.lastname: Wamil
authors.forename: G B
authors.initials: GB
authors.lastname: Thurman
authors.forename: P A
authors.initials: PA
authors.lastname: Minton
authors.forename: H W
authors.initials: HW
authors.lastname: Sundell
authors.forename: H P
authors.initials: HP
authors.lastname: Yan
authors.forename: C E
authors.initials: CE
authors.lastname: Carter
authors.forename: Y F
authors.initials: YF
authors.lastname: Wang
authors.forename: G E
authors.initials: GE
authors.lastname: York
authors.forename: M H
authors.initials: MH
authors.lastname: Zhang
authors.forename: D H
authors.initials: DH
authors.lastname: Johnson
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D016207:Cytokines / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000098:blood supply* / Q000188:drug therapy*; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D011135:Polysaccharides, Bacterial / Q000008:administration & dosage / Q000009:adverse effects*; D012882:Skin Tests
chemical_list: D000970:Antineoplastic Agents; D016207:Cytokines; D011135:Polysaccharides, Bacterial; C032263:streptococcal polysaccharide type III group B