A single low dose of rasburicase for treatment of hyperuricemia in patients with malignant diseases

Hyperuricemia is a major feature of tumor lysis syndrome (TLS) in patients with hematololoic malignancies. Because of high tumor burden or pre-existing renal dysfunction, a conventional approach with hydration, alkalinization, and allopurinol may not be sufficient to lower uric acid levels rapidly. Rasburicase, a recombinant urate oxidase enzyme, converts uric acid to soluble allantoin reducing the risk of renal events. The approved dose is 0.15-0.2 mg/kg/d for 3-7 days. The cost is $255/mg corresponding to approximately $15,000/5day for an average adult. Having had success with variable lower doses and frequency in a small number of patients (Trifilio et al, ASH 2004), we treated patients with fixed single doses of the drug with close monitoring of biochemical parameters. Patients received hydration and allopurinoal as well. Records of 51 patients treated with single-dose rasburicase were reviewed with IRB approval. The rasburicase dose used was 3 mg (n = 44), 4.5 mg (n = 3), or 6 mg (n = 4). The mean baseline uric acid for the 3 mg group was 10.2 and serum creatinine was 2.9, and for the combined 4.5/6 mg group, 13 and 2.7. After a single 3 mg dose, mean uric acid and creatine fell to 5.7 (44% decline) and 2.7 (7% decline) at 24 hours and 4.0 (61% decline) and 2.5 (14% decline) at 48 hours, respectively. Uric acid levels were in the normal range (≤8) in 91% of patients at 24 hours and in all at 48 hours. After a single 4.5/6 mg dose, uric acid and creatinine fell to 8.8 (32% decline) and 2.3 (15% decline) at 24 hours and 4.8 (63% decline) and 2.2 (19% decline) at 48 hours, respectively. Uric acid levels were within the normal range at 48 hours in all 7 patients. Importantly, uric acid levels at 24 hours were within the normal range in 46 of 47 patients with baseline uric acid ≤15. All 51 patients, including those with baseline uric acid >15, achieved nomral levels within 48 hours. A week after rasburicase, all 51 patients had maintained uric acid levels ≤8, and had experienced improvement in creatine to 2.0. No additional renal dysfunction developed in any patient, and no patient required hemodialysis (myeloma patients with end-stage renal disease undergoing HSCT continued hemodialysis). We conclude that a single low dose of rasburicase is effective in lowering elevated serum uric acid levels to normal with preservation of renal function. Significant cost savings with this approach (94-97% cost reduction) should reduce the reluctance to use rasburicase in patients with elevated uric acid levels.