Prevention and treatment of tumor lysis syndrome, and the efficacy and role of rasburicase

Abstract

Tumor lysis syndrome (TLS) is a potentially life-threatening condition that occurs in oncologic and hematologic patients with large tumor burden, either due to cytotoxic therapy or, less commonly, spontaneously because of massive tumor cell lysis. TLS is clinically characterized by acute renal failure, hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcemia. While limited options are available for treating TLS, identifying patients at high risk for developing TLS and prevention in high-risk patients remain an important aspect in the treatment of cancer patients. In general, treatment of TLS consists of intensive hydration, stimulation of diuresis, and, more specifically, in the use of allopurinol and rasburicase. Rasburicase, a recombinant urate oxidase, rapidly and effectively reduces hyperuricemia, which subsequently significantly decreases the risk of acute renal failure and other clinical manifestations of TLS. For this review, a comprehensive literature search using the term “tumor lysis syndrome” and/or “rasburicase” was performed considering articles listed in MEDLINE. Incidence, prevention, and therapy of TLS with a special focus on the role of rasburicase are discussed. We evaluated 120 relevant articles including 35 case reports, 32 clinical trials, and 14 meta-analyses.

Spontaneous Tumor Lysis Syndrome

“…As a result, a smaller quantity of poorly soluble uric acid is formed and the water-soluble xanthine and hypoxanthine can be excreted through the kidneys. The dosage should be reduced in patients with kidney disease [ 23 ]. The advantages of this therapeutic measure are low cost and oral administration, while its disadvantage is a delayed onset of action by 24–72 h. As a result, allopurinol can only be used to a limited extent in the presence of high uric acid levels (≥476 μmol/L).…”

“…The advantages of this therapeutic measure are low cost and oral administration, while its disadvantage is a delayed onset of action by 24–72 h. As a result, allopurinol can only be used to a limited extent in the presence of high uric acid levels (≥476 μmol/L). The increased xanthine and hypoxanthine volumes also make it necessary to consider the risk of xanthine-induced renal failure as a differential diagnosis [ 4 , 7 , 23 ].…”

Recombinant production of Aspergillus Flavus uricase and investigation of its thermal stability in the presence of raffinose and lactose

“…Allopurinol, a competitive inhibitor of xanthine oxidase is a common agent for blocking the conversion of hypoxanthine and xanthine to uric acid (Pession et al 2008), and thereby, allopurinol reduces uric acid production not its conversion to uric acid and hence excretion. In addition, UOX from Aspergillus flavus (Rasburicase) is mostly used for treatment of gout disease and hyperuricemia occurring in TLS (Alakel et al 2017). The advantage of urate oxidase treatment over allopurinol is that it reduces preexisting hyperuricemia and does not lead to accumulation of xanthine or hypoxanthine which occurs after allopurinol uptake.…”

Onconephrology: The intersections between the kidney and cancer

“…38 For patients who present for treatment with elevated uric acid levels (>8 mg/dL), treatment with recombinant urate oxidase (rasburicase) is recommended to rapidly (within 24 hours) lower uric acid levels. 40 Rasburicase converts uric acid to a soluble compound (allantoin) that is readily excreted in the urine. Rasburicase does lead to the production of hydrogen peroxide in this process and thus there is a risk of methemoglobinemia and hemolytic anemia in susceptible patients (those with glucose-6-phosphate dehydrogenase deficiency).…”