A randomized comparison between rasburicase and allopurinol in children with lymphoma or leukemia at high risk for tumor lysis

Standard therapy in the United States for malignancy-associated hyperuricem ia consists of hydration, alkalinization, and allopurinol. Urate oxidase ca talyzes the enzymatic oxidation of uric acid to a 5 times increased urine s oluble product, allantoin. Rasburicase is a new recombinant form of urate o xidase available for clinical evaluation. This multicenter randomized trial compared allopurinol to rasburicase in pediatric patients with leukemia or lymphoma at high risk for tumor lysis. Patients received the assigned uric acid-lowering agent for 5 to 7 days during induction chemotherapy. The pri mary efficacy end point was to compare the area under the serial plasma uri c acid concentration curves during the first 96 hours of therapy (AUC(0-96) ). Fifty-two patients were randomized at 6 sites. In an intent-to-treat ana lysis, the mean uric acid AUC(0-96) was 128 +/- 70 mg/dL.hour for the rasbu ricase group and 329 +/- 129 mg/dL.hour for the allopurinol group (P<.0001) . The rasburicase versus allopurinol group experienced a 2.6-fold (95% CI: 2.0-3.4) less exposure to uric acid. Four hours after the first dose, patie nts randomized to rasburicase compared to allopurinol achieved an 86% versu s 12% reduction (P<.0001) of initial plasma uric acid levels. No antirasbur icase antibodies were detected at day 14. This randomized study demonstrate d more rapid control and lower levels of plasma uric acid in patients at hi gh risk for tumor lysis who received rasburicase compared to allopurinol. F or pediatric patients with advanced stage lymphoma or high tumor burden leu kemia, rasburicase is a safe and effective alternative to allopurinol durin g initial chemotherapy. (Blood. 2001; 97:2998-3003) (C) 2001 by The America n Society of Hematology.