A randomized trial of a single-dose rasburicase versus five-daily doses in patients at risk for tumor lysis syndrome

Abstract

Background: Tumor lysis syndrome (TLS) is a life-threatening disorder characterized by hyperuricemia and metabolic derangements. The efficacy of rasburicase, administered daily for 5 days, has been well established. However, the optimal duration of therapy is unknown in adults.

Patients and methods: We evaluated the efficacy of rasburicase (0.15 mg/kg) administered as single dose followed by as needed dosing (maximum five doses) versus daily dosing for 5 days in adult patients at risk for TLS.

Results: Eighty of the 82 patients enrolled received rasburicase; 40 high risk [median uric acid (UA) 8.5 mg/dl; range, 1.5-19.7] and 40 potential risk (UA = 5.6 mg/dl; range, 2.4-7.4). Seventy-nine patients (99%) experienced normalization in their UA within 4 h after the first dose; 84% to an undetectable level (<0.7 mg/dl). Thirty-nine of 40 (98%) patients in the daily-dose arm and 34 of 40 (85%) patients in single-dose arm showed sustained UA response. Six high-risk patients within the single-dose arm required second dose for UA >7.5 mg/dl. Rasburicase was well tolerated; one patient with glucose-6-phosphate dehydrogenase deficiency developed methemoglobinemia and hemolysis.

Conclusions: Rasburicase is highly effective for prevention and management of hyperuricemia in adults at risk for TLS. Single-dose rasburicase was effective in most patients; only a subset of high-risk patients required a second dose.

Figure 1.

CONSORT diagram. Patient enrollment and randomization.

Figure 2.

(A) Plasma uric acid (UA) levels (mean ± SEM) during the study period. Left panel shows plasma UA profile over the study period in arm A stratified by the risk group. Right panel shows plasma UA profile over the study period in arm B stratified by the risk group. (B) Timing of a second dose of rasburicase in a subset of high-risk patients within arm A requiring additional therapy. Five patients needed a second dose of rasburicase during the study period (days 2–5). Two patients on day 3, one patient on day 4, and two patients on day 5.