Effectiveness and Safety of Allopurinol, Febuxostat, and Rasburicase in the Prevention of Tumor Lysis Syndrome: A Systematic Review and Network Meta-analysis

Abstract

Although prevention is vital in managing tumor lysis syndrome (TLS), no study directly compares various regimens. This study compared the effectiveness and safety of urate-lowering agents in preventing TLS. Databases were searched for randomized controlled trials involving adults with hematologic or solid malignancies on chemotherapy or cytoreductive agents given allopurinol, febuxostat, or rasburicase alone or in combination at any dose, form, or frequency published in English by December 2021. Outcomes included laboratory and clinical TLS expressed as relative risks, adverse events as described by authors, and mean serum uric acid (sUA) as mean differences of area under the curve. A network of meta-analysis and post-hoc meta-analysis based on TLS risk using a random-effects model was done using Stata 14.0 and Review Manager 5.3, respectively. Certainty of evidence was assessed using the GRADE approach. Three studies with a total of 633 participants given allopurinol, febuxostat, rasburicase, or rasburicase combined with allopurinol were included. Rasburicase is more effective than allopurinol in preventing laboratory TLS (relative risk: 0.51; 95% confidence interval [CI]: 0.32–0.81) based on moderate quality evidence. No significant differences were observed in clinical TLS. Adverse events were attributable to toxicities of chemotherapy. Rasburicase alone or in combination with allopurinol was better than allopurinol or febuxostat alone in reducing sUA level. Febuxostat is more effective than allopurinol in lowering sUA levels among patients at high-risk of TLS (mean difference −125.75; 95% CI: −223.47 to −28.02). Rasburicase may be the most effective agent in preventing laboratory TLS and maintaining low sUA levels.