Pharmacology of Escherichia coli-L-asparaginase polyethylene glycol adduct.
The polyethylene glycol (PEG) adduct of Escherichia coli L-asparaginase was administered intravenously to 4 patients with chemotherapy refractory cancers. The PEG-enzyme in plasma exhibited a half-life of 16-25 days. Doses of 250IU/m2 or greater reduced plasma asparagine to undetectable levels for as long as enzyme was detectable in plasma. All doses of enzyme administered (250-1000 IU/m2) caused similar increases in plasma aspartate, i.e. no dose-response relationship. Pleural fluid and ascites contained detectable enzyme but at a value 10-15% of simultaneously drawn plasma levels. Toxicity in this small group of patients was minimal; nausea and transient fever predominated. There were no clinical signs of PEG-asparaginase-induced pancreatitis, renal dysfunction, hypocalcemia and hyperglycemia. No patient developed evidence of a PEG-asparaginase allergic reaction; no patient formed antibodies to asparaginase or PEG-asparaginase. Two patients with large cell lymphoma showed a partial response to treatment.
D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001215:Asparaginase / Q000008:administration & dosage* / Q000009:adverse effects / Q000378:metabolism; D004926:Escherichia coli / Q000201:enzymology*; D006801:Humans; D008297:Male; D009369:Neoplasms / Q000188:drug therapy*; D011092:Polyethylene Glycols / Q000008:administration & dosage*
D000970:Antineoplastic Agents; D011092:Polyethylene Glycols; D001215:Asparaginase