Metabolic functions of the liver during chemotherapy in children with acute lymphoblastic leukemia.
OBJECTIVE
The purpose of the present work was estimation of liver function using the phenazone test and commonly used biochemical tests in children with acute lymphoblastic leukemia (ALL) during anticancer treatment.


METHODS
Observations were carried out in the same 21 patients with ALL before the beginning of chemotherapy, after Protocol I and after Protocol M of the antileukemic treatment carried out according to the program BFM 86.


RESULTS
The applied chemotherapy inhibited phenazone elimination. Both phenazone half-life and metabolic clearance rate were significantly different in patients after treatment with anticancer drugs, especially with high-dose of methotrexate (MTX), from those in patients before the beginning of chemotherapy (p < 0.001). Moreover, after MTX administration transaminases activity and serum bilirubin concentration were significantly higher than before treatment (p < 0.05).


CONCLUSIONS
Our results showed that in children with acute lymphoblastic leukemia, anticancer chemotherapy decreased liver metabolic capacity. Particularly, high-dose methotrexate treatment altered the elimination of phenazone by inhibiting the activity of hepatic mixed function oxidase system. This change may lead to an increase in toxicity of active drugs which are metabolized by this enzyme system. In addition, altered activity of liver metabolic function can impair transformation of prodrugs to active forms. It should be considered in selection of individual drug dosages. The objective estimation of the type and degree of liver dysfunction can only be achieved by the combination of a quantitative phenazone dynamic test and static biochemical tests.
Wiela-Hojenska
A
A
Department of Clinical Pharmacology, Wroclaw Medical University, Poland.
Gorczynska
E
E
Orzechowska-Juzwenko
K
K
Golebiowski
W
W
Hurkacz
M
M
Boguslawska-Jaworska
J
J
D000704:Analysis of Variance; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000097:blood / Q000493:pharmacokinetics*; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use*; D000983:Antipyrine / Q000097:blood / Q000493:pharmacokinetics*; D002648:Child; D002675:Child, Preschool; D006207:Half-Life; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008111:Liver Function Tests; D008657:Metabolic Clearance Rate; D008727:Methotrexate / Q000009:adverse effects / Q000627:therapeutic use*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000964:Antimetabolites, Antineoplastic; D000983:Antipyrine; D008727:Methotrexate