6-Mercaptopurine dose escalation and its effect on drug tolerance in childhood lymphoblastic leukaemia

Cancer Chemotherapy and Pharmacology
J C Welch, J S Lilleyman

Abstract

Daily oral 6-mercaptopurine (6MP) is important in the treatment of childhood lymphoblastic leukaemia (ALL), but there is great inter-patient variability in the pattern of evident drug effect (myelosuppression) seen at a standard dose. In an attempt to reduce that variability the current practise in the United Kingdom for the last 4 years has been to escalate the amount prescribed in patients who do not experience cytopenias at 75 mg/m2. We undertook a study to see whether that strategy would increase the total dose of 6MP prescribed in such patients and whether it would alter the pattern of myelosuppression. Over a 6-month period we studied 44 children treated conventionally (without escalation) and compared them with another 44 (matched for sex) who were treated on the same protocol but where doses were increased in monthly 25% steps if 75 mg/m2 was tolerated without cytopenias. We then compared the two groups for the total dose of drug prescribed and the frequency and duration of neutropenia or thrombocytopenia. The median cumulative dose of 6MP received by the conventionally treated children (10,002 mg/m2) was not significantly different from that of the children treated with dose escalation (9,429 mg/m2). In a comparison of...Continue Reading

Citations

May 10, 2008·Chemical Biology & Drug Design·Marcio L De PaulaAna Paula Ferreira
Feb 18, 2011·Pediatric Blood & Cancer·Smita Bhatia
Dec 7, 2000·Clinical Pharmacokinetics·F InnocentiM J Ratain
Oct 13, 2020·Journal of Oncology Pharmacy Practice : Official Publication of the International Society of Oncology Pharmacy Practitioners·A C WhileyT MacDonald

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