Pharmacology of Escherichia coli-L-asparaginase polyethylene glycol adduct

Anticancer Res. 1981;1(6):373-6.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antineoplastic Agents / administration & dosage*
  • Asparaginase / administration & dosage*
  • Asparaginase / adverse effects
  • Asparaginase / metabolism
  • Escherichia coli / enzymology*
  • Humans
  • Male
  • Neoplasms / drug therapy*
  • Polyethylene Glycols / administration & dosage*

Substances

  • Antineoplastic Agents
  • Polyethylene Glycols
  • Asparaginase