A PHASE-I CLINICAL AND PHARMACOKINETIC STUDY OF THE ANGIOGENESIS INHIBITOR, TECOGALAN SODIUM

Background: Tecogalan sodium is an angiogenesis inhibitor isolated fro m a sulfated polysaccharide produced by the bacterium Arthrobacter. Th e antiangiogenic effect of tecogalan sodium is thought to be mediated by the inhibition of binding of basic fibroblast growth factor to cell ular receptors. Patients and methods: A phase I study was conducted in thirty-three patients with refractory malignancies, including AIDS-as sociated Kaposi's sarcoma. Patients received a single i.v. infusion ev ery 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/m(2)). Results: The primary dose-limiting t oxicity 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 rigor s (31%) which were well controlled with acetominophen and meperidine. The serum half-life of tecogalan sodium was between 1-1.5 hours and <2 5% of unchanged drug was excreted in the urine. Conclusions: The recom mended phase II dose of tecogalan sodium on this schedule is 390 mg/m( 2) over 24 hours. Other schedules including continuous administration should be investigated to maximize the efficacy of this novel angiogen esis inhibitor.