Urate oxidase for the prevention and treatment of tumor lysis syndrome in children with cancer
Abstract
Background
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.
Objectives
We aimed to determine the effectiveness and safety of urate oxidase in the prevention and treatment of TLS in children with malignancies.
Search methods
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).
Selection criteria
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.
Data collection and analysis
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.
Main results
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.
Authors' conclusions
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.
PICOs
Plain language summary
Urate oxidase for the prevention and treatment of complications from massive lysis (breakdown) of tumor cells in children with cancer
Tumor lysis syndrome occurs when uric acid and other cellular substances are rapidly released into the circulation when tumor cells are broken down spontaneously or during treatment. Uric acid has low solubility (does not dissolve easily), therefore it can build up in the kidney resulting in kidney failure and possibly death eventually. Urate oxidase is an enzyme that can be administered to patients at risk of tumor lysis syndrome to convert uric acid to a more soluble product, allantoin, which can be excreted by the kidneys more readily. Therefore, urate oxidase may be able to prevent or treat tumor lysis syndrome in patients with malignancies. However, the current systematic review of (randomized) controlled clinical trials found that although urate oxidase might be effective in reducing serum uric acid level, it has not been shown to reduce renal failure or mortality from tumor lysis syndrome in children with cancer.
