Single-Dose Rasburicase 6 mg in the Management of Tumor Lysis Syndrome in Adults

Abstract

Rasburicase is currently approved at a dosage of 0.15-0.2 mg/kg once/day for 5 days in pediatric patients with cancer to lower plasma uric acid concentrations and manage tumor lysis syndrome (TLS). Information on rasburicase dosing in adults is limited, with some data on using rasburicase as a single dose instead of multiple daily doses. Therefore, we evaluated the efficacy of a single dose of rasburicase for preventing or managing TLS in adults. We collected retrospective data for 11 adults with hematologic malignancies who received a single 6-mg dose of rasburicase. All patients received intravenous hydration with urinary alkalinization and allopurinol; however, due to adverse reactions, two patients received short courses of allopurinol. Only patients at high risk for TLS (e.g., large tumor burden, increasing uric acid concentration) or those with TLS received rasburicase. The single dose of rasburicase 6 mg resulted in a median 0.0773-mg/kg dose (range 0.0232-0.1361 mg/kg). The single 6-mg dose rapidly lowered uric acid concentrations in 10 of the 11 patients. The median uric acid concentration of 11.7 mg/dl (range 7.4-17.4 mg/dl) declined to 2.0 mg/dl (range 0.5-15.4 mg/dl) within a day after rasburicase administration (p=0.022). In these 10 patients, uric acid concentrations remained low despite subsequent chemotherapy, and none required additional rasburicase doses. The only patient who did not respond to the single 6-mg rasburicase dose was a morbidly obese man (259 kg, body mass index 87 kg/m2) who subsequently responded to an additional dose of rasburicase 12 mg. These results warrant further investigation of a single 6-mg dose of rasburicase in adults with TLS or at high-risk for developing TLS.

Management of tumor lysis syndrome with a single fixed dose of rasburicase in Asian lymphoma patients: A case series and literature review

“…In these 10 patients, uric acid concentrations remained low despite subsequent chemotherapy and none required additional rasburicase doses. 11 A similar efficacy of single dose rasburicase was also observed in our case series with patients who were predominantly Chinese. Several small-scale studies [4][5][6][7][8] have also shown that a single dose of rasburicase produces a rapid uric acidlowering effect that is beneficial for patients manifesting TLS.…”

Reduced administration of rasburicase for tumor lysis syndrome: A single-institution experience

“…It is logical to block xanthine oxidase, which converts purine metabolites such as hypoxanthine and xanthine to UA, thereby reducing the production of UA (2,3,8). However, xanthine oxidase inhibitors do not reduce the already generated UA.…”

“…Allantoin is readily excreted by the kidneys. The UA-lowering efficacy of rasburicase is prompt and potent, and the administration of rasburicase appears to be extremely well tolerated (6)(7)(8)(9)(10). The approved method of administration in Japan is 0.2 mg/kg once daily, as an intravenous infusion administered over a 30-min period, for a maximum of seven days (11).…”

Onco-Nephrology

“…An expert panel convened in 2010, sponsored by the manufacturer of rasburicase (SanofiAventis), recommended the prophylactic use of rasburicase in adults with a high-risk malignancy, with other patients receiving rasburicase after chemotherapy in the setting of elevated uric acid levels (51). Several cohort studies have demonstrated persistently suppressed serum uric acid concentrations with one-time dosing; a dose of 0.15 mg/kg seems to be a clinically reasonable and cost-effective approach (62)(63)(64)(65)(66)(67)(68)(69)(70)(71)(72)(73)(74). Repeat dosing may be needed if uric acid remains at or increases above 8.0 mg/dl after the initial dose (75).…”