From the Guidelines
Prophylaxis for Tumor Lysis Syndrome (TLS) is essential for patients at high risk of developing this condition, particularly those with bulky or aggressive malignancies.
Recommended Prophylactic Measures
The following measures are recommended:
- Aggressive hydration with intravenous fluids to maintain a urine output of at least 100 mL/hour in adults (3 mL/kg/hour in children <10 kg body weight) 1
- Allopurinol 100 mg/m2 thrice daily (maximum 800 mg/day) for low-risk patients 1
- Rasburicase 0.20 mg/kg/day, infused over 30 minutes, for high-risk patients, administered at least four hours before the start of tumor-specific therapy and continued for at least 3-5 days 1
- Monitoring of electrolytes, renal function, and uric acid levels
- Consideration of urine alkalinization, although its use is controversial and not universally recommended 1
Patient Stratification
Patients should be stratified into low-risk, intermediate-risk, and high-risk categories to determine the appropriate prophylactic measures 1.
High-Risk Patients
High-risk patients should receive rasburicase and hydration in an inpatient setting 1.
Low-Risk Patients
Low-risk patients should receive oral allopurinol, hydration, and urine alkalinization 1. Prophylaxis should be initiated at least 48 hours before starting chemotherapy and continued for at least 3-5 days or until the risk of TLS has decreased 1.
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). A total of 275 adult patients received at least one dose of study drug The median age was 56 years, 62% were males, 80% were Caucasian, 66% had leukemia, 29% had lymphoma; 18% were hyperuricemic (uric acid >7. 5 mg/dL) at study entry. Patients in Arm A received Elitek for 5 days (n=92). Patients in Arm B received Elitek from day 1 through day 3 followed by oral allopurinol from day 3 through day 5 (overlap on day 3: Elitek and allopurinol administered approximately 12 hours apart) (n=92). The major endpoint of this study was the uric acid response rate defined as the proportion of patients with plasma uric acid levels ≤7. 5 mg/dL from day 3 to day 7, after initiation of antihyperuricemic treatment. 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 prophylaxis for Tumor Lysis Syndrome (TLS) is rasburicase (Elitek) administered at a dose of 0.2 mg/kg/day as a 30-minute infusion once daily for 5 days 2.
- Alternative regimen: Elitek from day 1 through day 3 followed by oral allopurinol from day 3 through day 5 (overlap on day 3: Elitek and allopurinol administered approximately 12 hours apart) 2.
- Key benefit: Rasburicase (Elitek) can effectively maintain plasma uric acid concentration within a target range, reducing the risk of clinical TLS 2.
From the Research
Prophylaxis for Tumor Lysis Syndrome (TLS)
The prophylaxis for Tumor Lysis Syndrome (TLS) includes:
- Aggressive fluid management
- Judicious use of diuretics and hypouricemic agents 3
- Allopurinol for low-risk cases 3
- Urate oxidase (e.g. rasburicase) for intermediate to high-risk cases 4, 3
- Correction of electrolytes and use of renal replacement therapy may also be required during treatment of TLS 3
Risk Stratification
Risk factors for TLS include:
- Biological evidence of laboratory TLS (LTLS)
- Proliferation, bulk and stage of malignant tumour
- Renal impairment and/or involvement at the time of TLS diagnosis 5
- Patients with high-tumor burden hemato-oncologic malignancies are at high risk for TLS 4, 6
- Patients with germ cell tumors (GCT) are classified as intermediate risk for TLS, but may be classified as high risk if they have other TLS risk factors 7
Prophylactic Measures
Prophylactic measures are widely available for patients at risk of TLS and are considered highly effective 6