The optimal single-dose regimen of rasburicase for management of tumour lysis syndrome in children and adults: a systematic review and meta-analysis

J Clin Pharm Ther. 2017 Feb;42(1):18-26. doi: 10.1111/jcpt.12479. Epub 2016 Nov 25.

Abstract

What is known and objective: To perform a meta-analysis exploring the optimal single-dose regimen for managing tumour lysis syndrome (TLS) in children and adults with haematological malignancies.

Methods: We systematically searched PubMed, MEDLINE, Web of Science, the Cochrane Library and the ClinicalTrials.gov website for studies regarding single-dose rasburicase in paediatric and adult patients with TLS. Data were analysed using Open MetaAnalyst statistical software.

Results: Fifteen adult studies (fourteen retrospective studies and one randomized controlled trial) and four observational studies using children were extracted, with a total of 906 and 92 subjects, respectively. Single doses of 1·5, 3, 4·5, 6, 7·5 mg and weight-based single doses of 0·05 and 0·15 mg/kg were compared. The response rate for 6, 7·5 mg and 0·15 mg/kg single doses was 90% (95% CI: 0·825-0·974), 98·6% (95% CI: 0·957-1·015) and 93·6% (95% CI: 0·864-1·007), respectively, and higher than other dosing regimens tested. The single doses of 6 mg and 0·15 mg/kg rasburicase decreased uric acid levels more than the other regimens, and the mean uric acid reduction was 8·45 mg/dL (95% CI, 7·51-9·38) and 10 mg/dL (95% CI, 8·58-11·42), respectively.

What is new and conclusion: Our meta-analysis revealed that, for adult patients, a single 6 mg rasburicase dose is sufficient to normalize and sustain lower uric acid and creatinine levels in adults with TLS. This dose, therefore, balances cost and efficacy of treatment. The 3- and 4·5-mg single dose can be considered if the baseline uric acid level <12 mg/dL, with close monitoring of clinical and biochemical parameters, and repeat dosing if required. The 1·5 mg and 0·15 mg/kg single dose were sufficient to manage TLS in children.

Keywords: adults; children; meta-analysis; rasburicase; single-dose regimen; tumour lysis syndrome.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Adult
  • Child
  • Humans
  • Observational Studies as Topic
  • Randomized Controlled Trials as Topic
  • Retrospective Studies
  • Tumor Lysis Syndrome / drug therapy*
  • Urate Oxidase / administration & dosage*

Substances

  • rasburicase
  • Urate Oxidase