The optimal single-dose regimen of rasburicase for management of tumour lysis syndrome in children and adults: a systematic review and meta-analysis

Abstract

SUMMARYWhat is known and objective: To perform a meta-analysis exploring the optimal single-dose regimen for managing tumour lysis syndrome (TLS) in children and adults with haematological malignancies. Methods: We systematically searched PubMed, MEDLINE, Web of Science, the Cochrane Library and the ClinicalTrials.gov website for studies regarding single-dose rasburicase in paediatric and adult patients with TLS. Data were analysed using Open MetaAnalyst statistical software. Results: Fifteen adult studies (fourteen retrospective studies and one randomized controlled trial) and four observational studies using children were extracted, with a total of 906 and 92 subjects, respectively. Single doses of 1Á5, 3, 4Á5, 6, 7Á5 mg and weight-based single doses of 0Á05 and 0Á15 mg/kg were compared. The response rate for 6, 7Á5 mg and 0Á15 mg/kg single doses was 90% (95% CI: 0Á825-0Á974), 98Á6% (95% CI: 0Á957-1Á015) and 93Á6% (95% CI: 0Á864-1Á007), respectively, and higher than other dosing regimens tested. The single doses of 6 mg and 0Á15 mg/kg rasburicase decreased uric acid levels more than the other regimens, and the mean uric acid reduction was 8Á45 mg/dL (95% CI, 7Á51-9Á38) and 10 mg/dL (95% CI, 8Á58-11Á42), respectively. What is new and conclusion: Our meta-analysis revealed that, for adult patients, a single 6 mg rasburicase dose is sufficient to normalize and sustain lower uric acid and creatinine levels in adults with TLS. This dose, therefore, balances cost and efficacy of treatment. The 3-and 4Á5-mg single dose can be considered if the baseline uric acid level <12 mg/dL, with close monitoring of clinical and biochemical parameters, and repeat dosing if required. The 1Á5 mg and 0Á15 mg/kg single dose were sufficient to manage TLS in children. WHAT IS KNOWN AND OBJECTIVETumour lysis syndrome (TLS) is a frequently encountered and lifethreatening oncologic emergency. It is characterized by severe electrolyte and metabolite abnormalities caused by rapid and massive breakdown of cancer cells and release of intracellular content into the systemic circulation, which leads to severe complications, such as hyperuricemia, hyperkalemia, hyperphosphatemia and hypocalcaemia.1,2 TLS occurs most commonly within 12-72 h after initiation of cytoreductive chemotherapy of haematological malignancies, especially in non-Hodgkin lymphoma and acute lymphocytic leukaemia (ALL), as well as in solid tumours that are characterized by high sensitivity to cytotoxic treatment, high proliferative rate or large tumour size or burden; however, it can also occur spontaneously without chemotherapy. 2-4Numerous studies have demonstrated that rasburicase is effective and safe in reducing uric acid (UA) levels and works within 4 h post-administration. [5][6][7][8] Rasburicase was approved by the US FDA for the treatment and prophylaxis of hyperuricemia in paediatric and adult patients with leukaemia, lymphoma or solid tumours who are receiving chemotherapy or at high risk of TLS, in 2002 and 2009, respectively. The recommended dose by the FDA i...

Rasburicase-induced Hemolytic Anemia in an Adolescent With Unknown Glucose-6-Phosphate Dehydrogenase Deficiency

“…The recommended dose of rasburicase is 0.15 to 0.2 mg/kg daily (maximum dose of 6 mg per our institutional guidelines) with a duration of therapy from 1 to 7 days. 17,18 Our patient's initial clinical presentation with a large tumor burden, diagnosis of T cell lymphoma, and significant risk of continued rise in uric acid with initiation of chemotherapy, placed him at a high risk for complications related to TLS. Given these concerns, therapy with rasburicase was administered.…”

“Disproportionate” hyperuricemia in children with hemolytic uremic syndrome (HUS): should we regard this as a “medical emergency”?

“…The results of 2 such studies by Jayabose et al [16] and Gopakumar et al [17], which Cho et al referenced in their decision to use a median dose of only 0.1 mg/kg, show inferior responses to those obtained with the recommended dose. A recent review and meta-analysis by Yu et al concluded that doses of 0.15 or 0.20 mg/kg are needed to produce excellent responses in young children with HU [18], confirming the findings reported by Pui et al [14].…”

Prevention and Treatment of Tumor Lysis Syndrome in the Era of Onco-Nephrology Progress

“…Alternatively, for patients with the low to moderate risk, a single fixed (3, 4.5, 6, or 7.5 mg) or weightbased (0.15-0.20 mg/kg) dose regimen has been proposed, and its efficacy is demonstrated [82][83][84][85][86][87][88]. A systematic review and meta-analysis of 19 studies by Yu et al [89] revealed that single doses of rasburicase: 6 mg for adults and 1.5 and 0.15 mg/kg for children, were sufficient to normalize and sustain lower uric acid and creatinine levels in adults with TLS. According to these authors, the 3-and 4.5-mg single doses can be considered if the baseline uric acid level is <12 mg/dL.…”

“…According to these authors, the 3-and 4.5-mg single doses can be considered if the baseline uric acid level is <12 mg/dL. In patients treated with the single-dose regimen, a reassessment of clinical and biochemical parameters is necessary, with repeating the dose if required [3,89]. Cortes et al [90] demonstrated that sequential therapy with rasburicase followed by allopurinol was similarly effective and may be a reasonable and cost-effective approach with similar efficacy in adults with hyperuricemia or at high risk for TLS.…”