How Can Tumor Lysis Syndrome Be Prevented and Managed in Cancer Patients?

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Table 1. Tumor lysis syndrome staging2

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Table 2. Cairo-Bishop clinical tumor lysis syndrome definition and grading30

TLS Prevention

Intravenous fluids. Every patient at intermediate or high risk of TLS should receive intravenous fluids (IVF) prior to cancer treatment; those at low risk may receive IVF based on the provider’s clinical judgment.³⁰ The purpose of administering IVF is to generate high urine output to reduce the risk of precipitation of uric acid in the renal tubules.³⁰ Both adults and children should receive approximately 2 to 3 L/m2 per day of IVF,30 and urine output should be maintained at 2 ml/kg/hr (or 4 to 6 ml/kg/hr for children <10kg).30 IVF should be cautiously administered in patients with renal insufficiency or heart failure, and diuretics may be used to maintain goal urine output. Recommended initial fluids are D51/4 normal saline, or normal saline for patients who are dehydrated or hyponatremic.³⁰

Allopurinol. Allopurinol is usually also administered to patients at risk for developing TLS.³⁰ Allopurinol inhibits the metabolism of hypoxanthine and xanthine to uric acid, which decreases the accumulation of uric acid in the renal tubules, thus preventing obstructive renal disease from precipitation of uric acid.⁴ The recommended dose of allopurinol is 100 mg/m2 every eight hours, and should not exceed 800 mg per day in adults. It should be started one to two days prior to induction chemotherapy and continued for three to seven days after the treatment and until uric acid levels and other electrolyte levels have returned to normal. The dose is adjusted to 50 mg/m2 every eight hours in patients with kidney failure.³⁰

In some cases, allopurinol can lead to increased levels of xanthine crystals in the renal tubules, leading to acute kidney injury. Also, allopurinol does not have any effect on uric acid that has already been formed, so patients with elevated uric acid levels prior to the initiation of cancer therapy will not have any reduction in the levels of uric acid. Allopurinol reduces the degradation of other purines, so it can cause toxicity in patients on azathioprine and 6-mercaptopurine if the doses of these medications are not adjusted.

Rasburicase. Rasburicase is a recombinant urate oxidase, derived from aspergillus favus, which catalyzes the breakdown of uric acid to allantoin, which is a water-soluble product. Rasburicase is recommended as a first-line treatment for patients at high risk for clinical TLS.³⁰ Rasburicase has an earlier onset than allopurinol and rapidly decreases serum levels of uric acid within four hours of administration.^30,31 The recommended dose is 0.10 to 0.20 mg/kg once a day for five days in adults.³⁰

A Phase III trial compared the efficiency and safety of rasburicase to rasburicase with allopurinol or allopurinol alone.³² A significantly higher normalization of uric acid was found in patients on rasburicase compared to allopurinol alone. The incidence of laboratory TLS was also significantly lower with rasburicase alone compared to allopurinol alone, and was even lower with allopurinol plus rasburicase. The incidence of acute kidney injury was the same with rasburicase alone or allopurinol alone but was higher with rasburicase plus allopurinol.

Serum uric acid, phosphorus, potassium, and calcium need to be monitored every four hours for 24 hours after the completion of chemotherapy in patients on rasburicase.⁴ The sample of blood drawn to check the uric acid levels has to be placed on ice and processed within four hours in order to avoid falsely lower levels of uric acid due to the conversion of uric acid to allantoin. Rasburicase is contraindicated in patients with G6PD deficiency and pregnant women, because one of the byproducts of uric acid breakdown is hydrogen peroxide, which can cause severe hemolysis and the formation of methemoglobin in these patients.³⁰