PEG-asparaginase (Oncaspar) 2500 U/m(2) BSA in reinduction and relapse treatment in the ALL/NHL-BFM protocols.
OBJECTIVE
As previous data had shown that only two-thirds of patients had the predicted activity time courses when PEG-asparaginase 1000 U/m(2) was used in reinduction after native E. coli asparaginase in induction treatment of acute lymphoblastic leukaemia (ALL), drug monitoring was performed with the use of a higher dose.


METHODS
Because one-third of patients had insufficient serum asparaginase activity time courses after a single dose of 1000 U/m(2) PEG-asparaginase during reinduction treatment, a dose of 2500 U/m(2) PEG-asparaginase, which is the approved dosage in Germany, was used in 39 reinduction and 20 relapse patients to determine whether prolongation of the activity time course may be possible with this higher dose, and to look for significant differences between reinduction and relapse patients.


RESULTS
After 1, 2 and 3 weeks, the mean activities were 1113 +/- 699 U/l, 231 +/- 259 U/l, and 13 +/- 35 U/l in the reinduction patients, and 1078 +/- 649 U/l, 165 +/- 195 U/l and 19 +/- 28 U/l in the relapse patients, respectively. There were a considerable number of patients with a substantially shortened activity time course in both groups. In 10 of 39 reinduction patients and in 7 of 24 doses during relapse treatment, only activities <100 U/l were found after 1 week with a further fast decline. No statistically significant differences between the two patient groups could be shown at any time-point.


CONCLUSIONS
Comparison of these data with activities after 1000 U/m(2) PEG-asparaginase showed no prolongation of the time with activity in the therapeutic range with the higher dose. Therefore, for a longer duration of therapeutic activity, administration of further doses is mandatory.
Müller
Hans-Joachim
HJ
Department of Pediatric Hematology/Oncology, University of Münster, Germany. muellerb@mailer.uni-marburg.de
Beier
Rita
R
da Palma
João Casimiro
JC
Lanvers
Claudia
C
Ahlke
Elvira
E
von Schütz
Volker
V
Gunkel
Martin
M
Horn
Alexander
A
Schrappe
Martin
M
Henze
Günter
G
Kranz
Karen
K
Boos
Joachim
J
D000293:Adolescent; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001215:Asparaginase / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy*; D008297:Male; D011092:Polyethylene Glycols / Q000493:pharmacokinetics / Q000627:therapeutic use*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D012008:Recurrence
D000970:Antineoplastic Agents; D011092:Polyethylene Glycols; C042705:pegaspargase; D001215:Asparaginase