Pegylated asparaginase in combination with high-dose methotrexate for consolidation in adult acute lymphoblastic leukaemia in first remission: a pilot study.
The German Multicentre acute lymphoblastic leukaemia (ALL) study group (GMALL) performed a pilot study using pegylated asparaginase (PEG-ASP) in combination with high-dose methotrexate as consolidation therapy in the 05/93 protocol. The aim of the study was an intra-individual comparison of two different doses of PEG-ASP in 26 patients, with regard to the depletion of asparagine in serum and toxicity. 'Pharmacokinetic' monitoring was performed to evaluate the effect of an intra-individual dose escalation of PEG-ASP from 500 to 1000 U/m2 intravenously in successive doses. Serum asparaginase activity was targeted at > or =100 U/l for 1 week and > or =50 U/l for 10 d. The second course of PEG-ASP was administered to 23 patients. Due to hypersensitivity reactions in five patients, only 18 patients were evaluable for pharmacokinetic monitoring. With respect to the PEG-ASP activity, an effective depletion of asparagine could be postulated in the majority of patients during 10 d after the first administration. The effect of an intraindividual dose escalation form 500 to 1000 U/m2 was evaluable in 17 of 22 patients. An increment in peak PEG-ASP activity >70% was observed in 65% of the patients. PEG-ASP was well tolerated. Despite the long half-life of PEG-ASP, neither pancreatic nor central nervous toxicities occurred among the 26 adult patients treated in this pilot study.
Rosen
O
O
Department of Haematology/Oncology, Charité Campus Virchow, Berlin, Germany.
Müller
H J
HJ
Gökbuget
N
N
Langer
W
W
Peter
N
N
Schwartz
S
S
Hähling
D
D
Hartmann
F
F
Ittel
T H
TH
Mück
R
R
Rothmann
F
F
Arnold
R
R
Boos
J
J
Hoelzer
D
D
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001215:Asparaginase / Q000008:administration & dosage / Q000009:adverse effects; D001216:Asparagine / Q000097:blood; D001777:Blood Coagulation / Q000187:drug effects; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008099:Liver / Q000187:drug effects; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D010865:Pilot Projects; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D012074:Remission Induction
D001216:Asparagine; D001215:Asparaginase; D008727:Methotrexate