Mercaptopurine in childhood leukaemia: the effects of dose escalation on thioguanine nucleotide metabolites.
The current U.K. trial protocol (UKALL XI) for childhood lymphoblastic leukaemia demands mercaptopurine (MP) dose escalation in children who tolerate daily 75 mg/m2 MP (100% dose) without cytopenias. The previous trial (UKALL X) did not. MP metabolism was studied in a group of UKALL XI children (n = 21) who tolerated 100% dosages and who were matched in this respect with a similar group of UKALL X children. Red blood cell MP derived thioguanine nucleotide (TGN) concentrations were measured in both groups under comparable conditions; at 75 mg/m2 MP there was no significant difference. MP dose escalation in the UKALL XI children produced higher TGN concentrations (TGNs at 100% vs 125% dosages, median difference 90 pmol/8 x 10(8) RBCs, 95% CI 25 to 165 pmol, P < 0.02). Assayed at the time of cytopenia induced dose reduction, the UKALL XI children had accumulated significantly higher TGN concentrations than the UKALL X children (median difference 78 pmol/8 x 10(8) RBCs, 95% CI 20 to 144, P < 0.02). These findings indicate that dose escalation in children tolerant of 100% MP dosages produces higher peak TGN concentrations.
University of Sheffield Department of Medicine and Pharmacology, Royal Hallamshire Hospital, Sheffield.
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L
Lennard
J
J
Welch
J S
JS
Lilleyman
D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000627:therapeutic use*; D002648:Child; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D015122:Mercaptopurine / Q000008:administration & dosage / Q000627:therapeutic use*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000378:metabolism
D000964:Antimetabolites, Antineoplastic; D015122:Mercaptopurine