What is the best treatment for a patient with tumor lysis syndrome (TLS) and hyperuricemia?

From the Guidelines

The most appropriate additional treatment for this patient with tumor lysis syndrome (TLS) and hyperuricemia is rasburicase, as it rapidly converts uric acid to allantoin, which is more soluble and easily excreted, and has been shown to be effective in reducing uric acid levels and preventing TLS-related complications 1.

Key Considerations

• Aggressive hydration with intravenous normal saline at 2-3 L/m²/day should be initiated immediately to maintain high urine output (100-200 mL/hour) and help excrete uric acid and phosphate.
• Rasburicase (0.1-0.2 mg/kg IV as a single dose) is the preferred agent for established hyperuricemia in TLS, as it rapidly converts uric acid to allantoin, which is more soluble and easily excreted.
• Allopurinol (100-300 mg orally every 8 hours or 200-400 mg/m²/day divided) is used primarily for prevention rather than treatment of established hyperuricemia, as it only prevents new uric acid formation.
• Urinary alkalinization is no longer recommended as it may promote calcium phosphate precipitation.
• Electrolyte abnormalities should be corrected concurrently: hyperkalemia may require calcium gluconate, insulin with glucose, sodium bicarbonate, or potassium binders; hyperphosphatemia is treated with phosphate binders; and hypocalcemia should only be treated if symptomatic.
• Hemodialysis should be considered for severe cases with renal failure, persistent electrolyte abnormalities, or fluid overload, as indicated by the latest guidelines 1.

Treatment Approach

• The patient should receive rasburicase and aggressive hydration, with close monitoring of urine output, electrolyte levels, and renal function.
• Electrolyte abnormalities should be corrected promptly, and hemodialysis should be considered if necessary.
• The patient's condition should be closely monitored, and treatment should be adjusted as needed to prevent TLS-related complications.

From the FDA Drug Label

Of the subset of 61 patients whose plasma uric acid level was elevated at baseline (≥8 mg/dL), plasma uric acid concentration was maintained by 4 hours for 72% of patients (44/61), by 24 hours for 80% of patients (49/61), by 48 hours for 92% of patients (56/61), by 72 hours for 98% of patients (60/61), and by 96 hours for 100% (61/61).

Table 2 presents the response rates in the three treatment arms. The response rate in arm A was significantly greater than in arm C (p=0. 0009).

Tumor Lysis Syndrome (TLS) Clinical TLS was defined by changes in at least two or more laboratory parameters for hyperuricemia, hyperkalemia, hyperphosphatemia and hypocalcemia and at least one of the following events occurring within 7 days of treatment: renal failure/injury, need for renal dialysis, and/or serum creatinine increase >1.5 ULN, arrhythmia or seizure.

The best treatment for a patient with tumor lysis syndrome (TLS) and hyperuricemia is Rasburicase (IV) 2.

• Key benefits of Rasburicase include:
  • Rapid reduction of plasma uric acid levels
  • Effective in preventing and treating hyperuricemia
  • Reduced risk of renal failure and other complications associated with TLS
• Clinical evidence supports the use of Rasburicase in patients at high risk of TLS, with response rates significantly higher than those treated with allopurinol alone. The patient's presentation with acute kidney injury, hyperuricemia, and hyperkalemia suggests TLS, making Rasburicase the most appropriate treatment choice.

From the Research

Treatment Options for Tumor Lysis Syndrome (TLS) and Hyperuricemia

The patient in question is experiencing acute kidney injury with elevated serum creatinine and blood urea nitrogen levels, diminished urine output, and hyperuricemia, which are all indicative of tumor lysis syndrome (TLS). The most appropriate additional treatment for this patient would be an agent that can effectively reduce uric acid levels.

Available Treatment Options

• Allopurinol: A xanthine oxidase inhibitor that prevents the production of uric acid but does not reduce existing uric acid levels.
• Febuxostat: Another xanthine oxidase inhibitor with a similar mechanism to allopurinol.
• Rasburicase: A recombinant urate oxidase enzyme that breaks down existing uric acid into allantoin, which is more soluble and easily excreted by the kidneys.
• Urinary Alkalinization: A method to increase the solubility of uric acid in the urine, but its effectiveness is debated and it may not be as effective as rasburicase in reducing uric acid levels.

Recommended Treatment

Based on the studies 3, 4, 5, 6, 7, rasburicase is the most effective treatment for hyperuricemia associated with tumor lysis syndrome. It acts rapidly to reduce uric acid levels and is generally well-tolerated. The studies demonstrate that rasburicase is more effective than allopurinol in controlling plasma uric acid levels and preventing tumor lysis syndrome.

Key Findings

• Rasburicase normalizes uric acid levels in a significant proportion of patients within 24 hours 3.
• Rasburicase is more effective than allopurinol in controlling plasma uric acid levels, especially in patients at high risk for TLS 4.
• Rasburicase acts on existing uric acid concentrations, providing a quicker therapeutic response than allopurinol 5.
• Rasburicase is a useful option for the prophylaxis or treatment of anticancer therapy-induced hyperuricemia in both adult and pediatric patients 5, 6, 7.