Pegasparaginase: where do we stand?
The use of unmodified asparaginases (ASP) in the management of pediatric and adult acute lymphoblastic leukemia (ALL) is well established. Despite its well-proven clinical efficacy, the use of unmodified Escherichia coli ASP (EC-ASP) has been limited by frequent toxicities, especially the development of hypersensitivity reactions and neutralizing antibodies, and by the need for frequent administration. To overcome these limitations, EC-ASP enzyme was covalently linked to monomethoxypolyethylene glycol (PEG), forming the pegylated ASP (PEG-ASP) (Oncaspar). PEG-ASP has a prolonged half-life and is associated with decreased immunogenicity when compared with EC-ASP. Clinical trials have demonstrated the efficacy, safety and tolerability of PEG-ASP administered intramuscularly, subcutaneously or intravenously as part of multi-agent chemotherapy regimens in the management of newly diagnosed and relapsed pediatric and adult ALL. Here we discuss the pharmacology, pharmacokinetics, clinical trial results and potential side effects of PEG-ASP.
Zeidan
Amer
A
Roswell Park Cancer Institute, Department of Medicine, Buffalo, New York 14263, USA.
Wang
Eunice S
ES
Wetzler
Meir
M
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001215:Asparaginase / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D001216:Asparagine / Q000378:metabolism; D002986:Clinical Trials as Topic; D004342:Drug Hypersensitivity / Q000209:etiology; D019008:Drug Resistance, Neoplasm; D006801:Humans; D011092:Polyethylene Glycols / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy
D000970:Antineoplastic Agents; D011092:Polyethylene Glycols; D001216:Asparagine; C042705:pegaspargase; D001215:Asparaginase