Tumor lysis syndrome (TLS) is a potentially life-threatening complication of
cancer therapy characterized by two or more of the following laboratory abnormalities:
hyperuricemia,
hyperkalemia,
hypocalcemia, and
hyperphosphatemia, with resultant end-organ damage, eg,
renal failure,
seizures, or
cardiac arrhythmias. High-risk patients include those with highly proliferative
cancers and/or large
tumor burdens, particularly in the setting of highly effective
chemotherapy, among other risk factors. Before 2002,
antihyperuricemic drug therapy was limited to
allopurinol, a
xanthine oxidase inhibitor.
Rasburicase, a recombinant
urate oxidase, was approved by the US Food and Drug Administration for children in 2002 and adults in 2009, ushering in a new era in TLS
therapy. We attempted to critically appraise the available evidence supporting the perceived benefits of
rasburicase in the management of TLS. A Medline search yielded 98 relevant articles, including 26 retrospective and 22 prospective studies of
rasburicase for the treatment of TLS, which were then evaluated to determine the best available evidence for the effectiveness of
rasburicase in terms of disease-oriented, patient-oriented, and economic outcomes.
Rasburicase is now a standard of care for patients at high risk of TLS despite continuing debate on the correlation between its profound and rapid lowering of plasma
uric acid levels with hard patient outcomes, eg, need for
renal replacement therapy and mortality.
Rasburicase is dramatically effective in lowering plasma
uric acid levels. The mortality and cost-effectiveness benefits of this expensive
drug remain to be conclusively proven, and well designed, randomized controlled trials are needed to answer these fundamentally important questions.