A single, fixed dose of rasburicase (6 mg maximum) for treatment of tumor lysis syndrome in adults

To the Editor: Tumor lysis syndrome (TLS) is an oncologic emergency characterized by hyperuricemia, hyperkalemia, hyperphosphatemia, hypocalcemia, and oliguric renal failure (1). Management of TLS requires initiation of preventive measures in high-risk patients such as hydration, allopurinol, and ⁄or alkalinization. Also, rasburicase, a recombinant form of urate oxidase enzyme, should be considered for high-risk groups as both preventive and therapeutic modality. Rasburicase converts uric acid to allantoin, and this metabolite is inactive and 10–15 times more soluble than uric acid. This increased solubility leads to a more efficient excretion of this extracellular product (2, 3). Currently, the United States guidelines (4) recommend that rasburicase (Elitek ; Sanofi-aventis U.S. LLC, Bridgewater, NJ, USA) be used in the adult and pediatric patients with high risk for TLS. Although the European Medicines Agency (5) (EMEA) and Food and Drug Administration (6) (FDA) recommended dosing range for rasburicase is 0.15– 0.2 mg ⁄kg ⁄d for 5 d, several studies have been published evaluating a shorter period and ⁄or a lower dosage (7– 15). A single-dosing strategy has shown to be effective in the TLS treatment. In fact, most US centers have a protocol of a flat dose ranging from 3 to 9 mg times one dose instead of using the FDA-approved dosing. As the ideal dose and schedule of rasburicase is still being explored, we conducted a retrospective study to evaluate the effectiveness and safety of a fixed maximum 6 mg of rasburicase in 15 patients with Tumor Lysis Syndrome at Jackson Memorial Hospital (JMH, Miami, FL, USA). In addition, the cost-avoidance of the implemented protocol was quantified. Institutional Review Board approval was obtained. During the 7 months of the study period, we included all the patients who received rasburicase for the treatment of TLS at our institution. Response was defined as a reduction in plasma uric acid to less than 8 mg ⁄dL within 24 h after the first administration. Paired t test was performed to analyze whether there were statistically significant differences between uric acid levels preand postrasburicase treatment. Statistical significance was defined at a P value of < 0.05. Analyses were conducted with the spss v 15.0 software (SPSS lberica, Madrid, Spain). Patient¢s baseline demographic and clinical characteristics are presented in Table 1. Other data collected were risk factors such as renal impairment, concomitant allopurinol administration, and the need for hemodialysis. In this study, most patients had high levels of white blood cells and lactate dehydrogenase (LDH) associated with large tumor burden and high risk of developing TLS. Three patients had renal infiltration with the tumor. Twenty-one rasburicase doses were given to 18 patients during 7 months of the study period. Fifteen patients were given single, fixed maximum dose rasburicase (0.15– 0.2 mg ⁄kg ⁄d up to 6 mg). Three patients received single, weight-based rasburicase (0.15–0.2 mg ⁄kg ⁄d without any dose capping). These three patients were excluded from the study evaluation because they did not meet the protocol criteria for dosage.