Urate oxidase for the prevention and treatment of tumor lysis syndrome in children with cancer

Abstract

Tumor lysis syndrome (TLS) is a serious complication of malignancies and can result in renal failure or death. Preliminary reports suggest that urate oxidase is highly effective in reducing serum uric acid. It is uncertain whether high quality evidence exists to support its routine use in children with malignancies. We aimed to determine the effectiveness and safety of urate oxidase in the prevention and treatment of TLS in children with malignancies. We performed a comprehensive search of the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library issue 2, 2009), MEDLINE (1966 to 2009), EMBASE (1980 to 2009) and CINAHL (1982 to 2009). Randomized controlled trials (RCT) and controlled clinical trials (CCT) evaluating urate oxidase for the prevention or treatment of TLS in children under 18 years with any malignancy. Two review authors independently extracted trial data and assessed individual trial quality. We used relative risk (RR) for binary data and mean difference (MD) for continuous data. We included five trials, involved 336 patients in the treatment groups and 458 patients in the control groups. One RCT and three CCTs compared urate oxidase and allopurinol. Two trials tested Uricozyme and two tested rasburicase for the prevention of TLS. The RCT showed no significant difference in mortality or renal failure between the treatment and the control groups. The frequency of normalization of uric acid (RR 19.09, 95% CI 1.28 to 285.41) and area under curve of uric acid (MD -201, 95% CI to -258.05 to -143.95) were significantly better in the treatment group. One patient developed hemolysis. One CCT reported significantly lower mortality due to TLS (RR 0.05, 95% CI 0.00 to 0.89) and lower incidence of renal failure (RR 0.13, 95% CI 0.05 to 0.35) in the treatment group. Another CCT found significantly lower uric acid in the treatment group at 72 hours (MD -98.33, 95% CI -170.66 to -26) and 168 hours (MD -103.67, 95% CI -179.00 to -28.34). All included trials are highly susceptible to biases.Another included RCT with 30 patients compared different doses of rasburicase (0.2 mg/kg versus 0.15 mg/kg), which demonstrated similar efficacy in the reduction of uric acid. Adverse events occurred in 20% of patients, including hemolysis, hypersensitivity and anemia. Although urate oxidase might be effective in reducing serum uric acid, it is still unclear whether this translates into a reduction in mortality or renal failure. Clinicians should weigh the potential benefits of reducing uric acid and uncertain benefits of preventing renal failure or mortality from TLS against the potential risk of adverse effects.