[Therapeutic alternatives to native L-asparaginase in the treatment of adult acute lymphoblastic leukemia].
L-asparaginase is an effective antineoplastic agent, which is an integral part of combination chemotherapy protocols for adult acute lymphoblastic leukemia. Its antitumor effect results from the depletion of asparagine, an amino acid essential to leukemia cells, and subsequent inhibition of protein synthesis leading to cytotoxicity. However, its use has been limited by a high rate of hypersensitivity reactions and development of neutrolizing anti-asparaginase antibodies, and by the need of frequent administration. To overcome these limitations modified versions of L-asparaginase (such as asparaginase from other sources, pegylated formulations, and asparaginase loaded into erythrocytes) have been recently proposed. Advantages of these therapeutic alternatives to native L-asparaginase and their results as part of preliminary clinical trials in adults have been outlined in this review.
Thomas
X
X
Hôpital Edouard-Herriot, Lyon, France. xavier.thomas@chu-lyon.fr
Cannas
G
G
Chelghoum
Y
Y
Gougounon
A
A
D000328:Adult; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001215:Asparaginase / Q000493:pharmacokinetics / Q000627:therapeutic use; D001216:Asparagine / Q000009:adverse effects / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D016974:Dickeya chrysanthemi / Q000201:enzymology; D004337:Drug Carriers; D004347:Drug Interactions; D004912:Erythrocytes; D004926:Escherichia coli / Q000201:enzymology; D006801:Humans; D011092:Polyethylene Glycols / Q000493:pharmacokinetics / Q000627:therapeutic use; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*
D000970:Antineoplastic Agents; D004337:Drug Carriers; D011092:Polyethylene Glycols; D001216:Asparagine; C042705:pegaspargase; D001215:Asparaginase