title: A phase I clinical and pharmacokinetic study of the angiogenesis inhibitor, tecogalan sodium.
abstract: BACKGROUND
  Tecogalan sodium is an angiogenesis inhibitor isolated from a sulfated polysaccharide produced by the bacterium Arthrobacter. The antiangiogenic effect of tecogalan sodium is thought to be mediated by the inhibition of binding of basic fibroblast growth factor to cellular receptors.
  
  
  METHODS
  A phase I study was conducted in thirty-three patients with refractory malignancies, including AIDS-associated Kaposi's sarcoma. Patients received a single i.v. infusion every three weeks with the infusion duration ranging from one to twenty-four hours. Seven different dosage levels were studied (125, 185, 240, 300, 390, 445, and 500 mg/m2).
  
  
  RESULTS
  The primary dose-limiting toxicity was prolongation of the activated partial thromboplastin time with peak times being between 1.0-4.0 times the upper limit of normal. This toxicity was ameliorated at a given dose level by prolonging the infusion time. Other common toxicities included fever (40%) and rigors (31%) which were well controlled with acetominophen and meperidine. The serum half-life of tecogalan sodium was between 1-1.5 hours and < 25% of unchanged drug was excreted in the urine.
  
  
  CONCLUSIONS
  The recommended phase II dose of tecogalan sodium on this schedule is 390 mg/m2 over 24 hours. Other schedules including continuous administration should be investigated to maximize the efficacy of this novel angiogenesis inhibitor.
authors.affiliation: Cancer Therapy and Research Center, University of Texas Health Science Center at San Antonio, USA.
authors.forename: S G
authors.initials: SG
authors.lastname: Eckhardt
authors.forename: H A
authors.initials: HA
authors.lastname: Burris
authors.forename: J R
authors.initials: JR
authors.lastname: Eckardt
authors.forename: G
authors.initials: G
authors.lastname: Weiss
authors.forename: G
authors.initials: G
authors.lastname: Rodriguez
authors.forename: M
authors.initials: M
authors.lastname: Rothenberg
authors.forename: D
authors.initials: D
authors.lastname: Rinaldi
authors.forename: R
authors.initials: R
authors.lastname: Barrington
authors.forename: J G
authors.initials: JG
authors.lastname: Kuhn
authors.forename: K
authors.initials: K
authors.lastname: Masuo
authors.forename: K
authors.initials: K
authors.lastname: Sudo
authors.forename: R
authors.initials: R
authors.lastname: Atsumi
authors.forename: T
authors.initials: T
authors.lastname: Oguma
authors.forename: L
authors.initials: L
authors.lastname: Higashi
authors.forename: S
authors.initials: S
authors.lastname: Fields
authors.forename: L
authors.initials: L
authors.lastname: Smetzer
authors.forename: D D
authors.initials: DD
authors.lastname: Von Hoff
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use* / Q000652:urine; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000503:physiopathology*; D011135:Polysaccharides, Bacterial / Q000009:adverse effects / Q000627:therapeutic use* / Q000652:urine; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D011135:Polysaccharides, Bacterial; C079061:tecogalan