title: Evaluation of L-asparaginase: polyethylene glycol conjugate versus native L-asparaginase combined with chemotherapy. A randomized double-blind study in canine lymphoma.
abstract: L-asparaginase is an enzyme that inhibits protein synthesis by the depletion of sources of L-asparagine, which is necessary for transformed lymphoid cells to proliferate. L-asparaginase is used in the treatment of childhood acute lymphoblastic leukemia. A problem with L-asparaginase therapy is the immunogenicity of the enzyme and the development of anaphylactic reactions. Canine lymphoma is a predominantly B-cell tumor with widespread disease; without treatment, dogs with lymphoma usually survive 1-2 months. Canine lymphoma will respond to L-asparaginase therapy. A randomized double-blind study evaluated a polyethylene glycol (PEG) conjugate L-asparaginase combined with chemotherapy (vincristine, cyclophosphamide, doxorubicin, and prednisone). Thirty-five dogs were randomized to the PEG L-asparaginase group, and 34 dogs were randomized to the native L-asparaginase group. Thirty dogs (85.7%) achieved a complete remission (CR) with a median time to relapse of 217 days, and 32 (94.1%) dogs in the native L-asparaginase group achieved a CR with a median time to relapse of 214 days (P greater than 0.05). The asparaginase was well tolerated in both groups. Two dogs in the native L-asparaginase group had severe allergic reactions, and one dog in the PEG asparaginase group had a generalized urticarial reaction after repeated injections. This study indicates that PEG L-asparaginase has equal therapeutic efficacy to native L-asparaginase.
authors.affiliation: Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin, Madison 53706.
authors.forename: E G
authors.initials: EG
authors.lastname: MacEwen
authors.forename: R C
authors.initials: RC
authors.lastname: Rosenthal
authors.forename: L E
authors.initials: LE
authors.lastname: Fox
authors.forename: A S
authors.initials: AS
authors.lastname: Loar
authors.forename: I D
authors.initials: ID
authors.lastname: Kurzman
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001215:Asparaginase / Q000009:adverse effects / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage; D004283:Dog Diseases / Q000188:drug therapy*; D004285:Dogs; D004311:Double-Blind Method; D004317:Doxorubicin / Q000008:administration & dosage; D004361:Drug Tolerance; D004800:Enzymes, Immobilized / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D008223:Lymphoma / Q000188:drug therapy / Q000662:veterinary*; D008297:Male; D011092:Polyethylene Glycols / Q000009:adverse effects / Q000627:therapeutic use*; D011241:Prednisone / Q000008:administration & dosage; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage
chemical_list: D004800:Enzymes, Immobilized; D011092:Polyethylene Glycols; D014750:Vincristine; C042705:pegaspargase; D004317:Doxorubicin; D003520:Cyclophosphamide; D001215:Asparaginase; D011241:Prednisone