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Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet]. Chichester, UK: John Wiley & Sons, Ltd; 2003-. doi: 10.1002/14651858.CD006945.pub4

Cochrane Database of Systematic Reviews: Plain Language Summaries [Internet].

Urate oxidase for the prevention and treatment of complications from massive lysis (breakdown) of tumour cells in children with cancer

This version published: 2017; Review content assessed as up-to-date: March 14, 2016.

Link to full article: [Cochrane Library]

Plain language summary

Review question

We reviewed the evidence of the effects and safety of urate oxidase for the prevention and treatment of tumour lysis syndrome (TLS) in children with malignancies.

Background

TLS occurs when uric acid and other cellular substances are rapidly released into the circulation when tumour cells are broken down spontaneously or during treatment. Uric acid does not dissolve easily, therefore it can build up in the kidney, resulting in kidney failure and possibly death. Urate oxidase is an enzyme that can be administered to people at risk of TLS to convert uric acid to allantoin, which is easily dissolved and then readily excreted by the kidneys. Therefore, urate oxidase may be able to prevent or treat TLS in people with malignancies.

Study characteristics

The evidence is current to March 2016.

We found seven trials (1074 participants). No new studies were identified in this update. Six studies compared urate oxidase and allopurinol. Three trials tested Uricozyme, and three trials tested rasburicase. One study (30 participants) compared different doses of rasburicase.

Key results

The current systematic review of (randomised) controlled clinical trials found that although urate oxidase might be effective in reducing serum uric acid level, it has not been confirmed to reduce renal failure or mortality from TLS in children with cancer. Adverse effects might be more common in people who receive urate oxidase compared with allopurinol. Urate oxidase needs to be further evaluated, especially in high‐risk patients, such as those with high‐risk leukaemia and lymphoma.

Quality of the evidence

The quality of evidence ranks from very low to low because of imprecise results, and all included trials were highly susceptible to biases.

Abstract

Background: Tumour lysis syndrome (TLS) is a serious complication of malignancies and can result in renal failure or death. Previous reviews did not find clear evidence of benefit of urate oxidase in children with cancer. This review is the second update of a previously published Cochrane review.

Objectives: To assess the effects and safety of urate oxidase for the prevention and treatment of TLS in children with malignancies.

Search methods: In March 2016 we searched CENTRAL, MEDLINE, Embase, and CINAHL. In addition, we searched the reference lists of all identified relevant papers, trials registers and other databases. We also screened conference proceedings and we contacted experts in the field and the manufacturer of rasburicase, Sanofi‐aventis.

Selection criteria: Randomised controlled trials (RCT) and controlled clinical trials (CCT) of 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 risk ratios (RR) for dichotomous data and mean difference (MD) for continuous data.

Main results: We included seven trials, involving 471 participants in the treatment groups and 603 participants in the control groups. No new studies were identified in the update. One RCT and five CCTs compared urate oxidase and allopurinol. Three trials tested Uricozyme, and three trials tested rasburicase for the prevention of TLS.

The RCT did not evaluate the primary outcome (incidence of clinical TLS). It showed no clear evidence of a difference in mortality (both all‐cause mortality (Fisher's exact test P = 0.23) and mortality due to TLS (no deaths in either group)), renal failure (Fisher's exact test P = 0.46), and adverse effects between the treatment and the control groups (Fisher's exact test P = 1.0). The frequency of normalisation of uric acid at four hours (10 out of 10 participants in the treatment group versus zero out of nine participants in the control group, Fisher's exact test P < 0.001) and area under the curve of uric acid at four days (MD ‐201.00 mg/dLhr, 95% CI ‐258.05 mg/dLhr to ‐143.95 mg/dLhr; P < 0.00001) were significantly better in the treatment group.

One CCT evaluated the primary outcome; no clear evidence of a difference was identified between the treatment and the control groups (RR 0.77, 95% CI 0.44 to 1.33; P = 0.34). Pooled results of three CCTs showed significantly lower mortality due to TLS in the treatment group (RR 0.05, 95% CI 0.00 to 0.89; P = 0.04); no clear evidence of a difference in all‐cause mortality was identified between the groups (RR 0.19, 95% CI 0.01 to 3.42; P = 0.26). Pooled results from five CCTs showed significantly lower incidence of renal failure in the treatment group (RR 0.26, 95% CI 0.08 to 0.89; P = 0.03). Results of CCTs also showed significantly lower uric acid in the treatment group at two days (three CCTs: MD ‐3.80 mg/dL, 95% CI ‐7.37 mg/dL to ‐0.24 mg/dL; P = 0.04), three days (two CCTs: MD ‐3.13 mg/dL, 95% CI ‐6.12 mg/dL to ‐0.14 mg/dL; P = 0.04), four days (two CCTs: MD ‐4.60 mg/dL, 95% CI ‐6.39 mg/dL to ‐2.81 mg/dL; P < 0.00001), and seven days (one CCT: MD ‐1.74 mg/dL, 95% CI ‐3.01 mg/dL to ‐0.47 mg/dL; P = 0.007) after therapy, but not one day (three CCTs: MD ‐3.00 mg/dL, 95% CI ‐7.61 mg/dL to 1.60 mg/dL; P = 0.2), five days (one CCT: MD ‐1.02 mg/dL, 95% CI ‐2.24 mg/dL to 0.20 mg/dL; P = 0.1), and 12 days (one CCT: MD ‐0.80 mg/dL, 95% CI ‐2.51 mg/dL to 0.91 mg/dL; P = 0.36) after therapy. Pooled results from three CCTs showed higher frequency of adverse effects in participants who received urate oxidase (RR 9.10, 95% CI 1.29 to 64.00; P = 0.03).

Another included RCT, with 30 participants, compared different doses of rasburicase (0.2 mg/kg versus 0.15 mg/kg). The primary outcome was not evaluated. No clear evidence of a difference in mortality (all‐cause mortality (Fisher's exact test P = 1.0) and mortality due to TLS (no deaths in both groups)) and renal failure (no renal failure in both groups) was identified. It demonstrated no clear evidence of a difference in uric acid normalisation (RR 1.07, 95% CI 0.89 to 1.28; P = 0.49) and uric acid level at four hours (MD 8.10%, 95% CI ‐0.99% to 17.19%; P = 0.08). Common adverse events of urate oxidase included hypersensitivity, haemolysis, and anaemia, but no clear evidence of a difference between treatment groups was identified (RR 0.54, 95% CI 0.12 to 2.48; P = 0.42).

The quality of evidence ranks from very low to low because of imprecise results, and all included trials were highly susceptible to biases.

Authors' conclusions: Although urate oxidase might be effective in reducing serum uric acid, it is unclear whether it reduces clinical TLS, renal failure, or mortality. Adverse effects might be more common for urate oxidase compared with allopurinol. Clinicians should weigh the potential benefits of reducing uric acid and uncertain benefits of preventing mortality or renal failure from TLS against the potential risk of adverse effects.

Editorial Group: Cochrane Childhood Cancer Group.

Publication status: New search for studies and content updated (no change to conclusions).

Citation: Cheuk DKL, Chiang AKS, Chan GCF, Ha SY. Urate oxidase for the prevention and treatment of tumour lysis syndrome in children with cancer. Cochrane Database of Systematic Reviews 2017, Issue 3. Art. No.: CD006945. DOI: 10.1002/14651858.CD006945.pub4. Link to Cochrane Library. [PubMed: 28272834]

Copyright © 2017 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

PMID: 28272834

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