Clinical and economic burden of tumor lysis syndrome among patients with chronic lymphocytic leukemia/small lymphocytic lymphoma: A real-world US retrospective study.

BACKGROUND: Tumor lysis syndrome (TLS) is a potentially fatal complication of antineoplastic treatments for hematologic malignancies, including chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). Patients developing TLS require intensive care, adding to the overall clinical and economic burden of CLL/SLL. OBJECTIVE: To analyze TLS-associated health care resource utilization (HCRU) and costs in patients with CLL/SLL treated with regimens associated with a high TLS risk (per treatment guidelines), ie, anti-CD20-based chemoimmunotherapy (CIT), lenalidomide, obinutuzumab, or venetoclax. METHODS: Adult patients with CLL/SLL in the MarketScan Databases (January 1, 2006, to April 30, 2020) initiated on CIT, lenalidomide, obinutuzumab, or venetoclax (index date) on or after January 1, 2007, were included in the analysis. Treatment-emergent TLS was defined as TLS occurring in the first 90 days of active treatment. The post-index period was divided into 30-day intervals until the end of the index regimen; intervals pre-TLS were non-TLS intervals and those starting from the TLS event were TLS intervals. Per-patient-per-month (PPPM) HCRU and costs were compared between TLS and non-TLS intervals using generalized linear models adjusted for baseline and time-varying confounders. The proportion of patients in the TLS cohort (patients with treatment-emergent TLS) and non-TLS cohort (patients with no treatment-emergent TLS) who switched treatment within 90 days post-index was compared using Kaplan-Meier rates with logrank P values. RESULTS: Among 6,343 patients with CLL/SLL, 71 (1.1%) developed treatment-emergent TLS (venetoclax: 11.5%; other regimens: 0.8%) after a mean (median) of 12.7 (7.0) days following treatment initiation (mean [median] duration of index regimen: 16.0 [10.0] months); 12 (0.2%) developed clinical TLS (venetoclax: 3.1%; other regimens: 0.1%). TLS was associated with 1.7 times more inpatient admissions (P < 0.001), 2 times more days of inpatient stay (P = 0.012), 22% fewer days of antineoplastic drug administration (P = 0.020), and $3,062 PPPM higher health care costs (P = 0.016), which were mainly driven by $1,688 PPPM higher inpatient costs (P = 0.044). Higher costs were observed among both patients who initiated venetoclax (TLS: $24,170; non-TLS: $20,091) and those who initiated other regimens (TLS: $8,746; non-TLS: $6,915). More patients in the TLS vs non-TLS cohort switched treatment in the first 90 days of treatment (12.6% vs 5.1%, P = 0.006). CONCLUSIONS: TLS was associated with a substantial cost burden (driven by inpatient costs) and higher rate of treatment switching (vs non-TLS cohort) in patients with CLL/SLL treated with CIT, obinutuzumab, lenalidomide, or venetoclax. The risk of treatment-emergent TLS and associated incremental HCRU and costs, as well as the potential impact on quality of life, should be weighed when evaluating the risk-benefit of therapies in CLL/SLL management. DISCLOSURES: Dr Rogers has received research funding from Genentech, AbbVie, Novartis, and Janssen (not for the present study); consulting fees from Acerta Pharma, AstraZeneca, Innate Pharma, Pharmacyclics, Genentech, and AbbVie; and travel funding from AstraZeneca. Mr Emond, Mr Kinkead, Ms Lafeuille, and Mr Lefebvre are employees of Analysis Group, Inc., which has provided paid consulting services to Janssen Scientific Affairs, LLC. Drs Lu and Huang are employees of Janssen Scientific Affairs, LLC, and stockholders of Johnson & Johnson. Ms Côté-Sergent was an employee of Analysis Group, Inc., at the time the study was conducted. This study was funded by Janssen Scientific Affairs, LLC. The sponsor was involved in the study design; data collection, analysis, and interpretation; manuscript writing; and the decision to publish the article.

Assessment of rasburicase utilization for tumor lysis syndrome management in pediatric and adult patients in the inpatient and outpatient settings.

INTRODUCTION: At Wake Forest Baptist Health, an adult tumor lysis syndrome pocket card was created in order to optimize management of tumor lysis syndrome and outline specific recommendations for the use of rasburicase. Due to the increased use of rasburicase at our institution and its cost, the purpose of this study was to evaluate the utilization of rasburicase for the management of tumor lysis syndrome in pediatric and adult patients in the inpatient and outpatient settings. METHODS: This was an observational, single-center, non-randomized, retrospective chart review conducted between September 2018 and August 2019. The primary objective was to evaluate the utilization of rasburicase and appropriateness for the management of tumor lysis syndrome in pediatric and adult patients based on the Wake Forest Baptist Health tumor lysis syndrome pocket card. The secondary objectives were to assess response to prophylactic and treatment doses of rasburicase and to quantify drug cost versus expense of rasburicase utilization. RESULTS: Overall, 64 patients (57 adults and 7 pediatric patients) were included in the study. Rasburicase use for tumor lysis syndrome indication adhered to the pocket card 64% of the time. Appropriate fluids and/or allopurinol were initiated in only 34% of patients. For monitoring, 80% of patients had all necessary tumor lysis syndrome laboratory values collected after rasburicase administration. All 11 patients (17%) who received rasburicase in the outpatient setting did not have follow-up labs collected. Of the patients who had tumor lysis syndrome laboratory values collected post rasburicase, 39% were appropriately timed to accurately assess efficacy of rasburicase with the median time of laboratory monitoring after rasburicase being 6.5 h. Response was observed with rasburicase 3 mg (92%), 6 mg (100%), and weight-based dosing (100%). The wholesale acquisition cost per patient was $5203 (1101-10,406). The potential cost savings of using the 3 mg dose versus the 6 mg dose for the patients who did not meet tumor lysis syndrome treatment recommendations based on the Wake Forest Baptist Health pocket card was estimated to be $36,419.46. CONCLUSION: There are several opportunities for improvement in tumor lysis syndrome management and rasburicase utilization at our institution. This study will lead to the implementation of formal restrictions for rasburicase use and selection of rasburicase dose. Updating the rasburicase order panel to include appropriate prophylaxis and require input of uric acid level, populating pertinent tumor lysis syndrome laboratory values on the order verification screen for pharmacists to appropriately assess if rasburicase meets the institution restriction criteria, and providing education to providers on the appropriate ordering and timing of labs.

Cost-effectiveness analysis of rasburicase over standard of care for the prevention and treatment of tumor lysis syndrome in children with hematologic malignancies in China.

Aims: To conduct a lifetime cost-effectiveness analysis (CEA) of rasburicase compared with standard of care (SOC) for tumor lysis syndrome (TLS) in children with hematologic malignancies from the Chinese healthcare system perspective. Materials and methods: The CEA was performed using a decision tree model with a lifetime horizon. The model explores the cost-effectiveness of rasburicase vs SOC for both preventing TLS and treating established TLS among pediatric patients with acute myeloid leukemia (AML), acute lymphoid leukemia (ALL), and non-Hodgkin's lymphoma (NHL). Both the prophylaxis-use model and treatment-use model incorporate long-term health states of the diseases: survival without TLS and death. The efficacy data of rasburicase and SOC were obtained from published literature. Drug costs, healthcare resource utilization (HRU), and adverse event (AE) management costs were obtained via a published study with clinical experts. Costs in US dollar and quality-adjusted life year (QALY) are reported, and incremental cost-effectiveness ratios (ICERs) were also calculated. Uncertainties due to parameter fluctuations in the model were assessed through one-way sensitivity analysis and probabilistic sensitivity analysis (PSA). Results: During TLS prevention, compared with SOC, the ICER of rasburicase treatment in China are $17,580.04/QALY, $5,783.45/QALY, and $5,391.00/QALY for pediatric patients with AML, ALL, and NHL, respectively. For the established TLS treatment, compared with SOC, the ICERs of rasburicase treatment are $2,031.18/QALY, $1,142.93/QALY, and $990.37/QALY for pediatric patients with AML, ALL, and NHL, respectively. Limitations: The clinical data for SOC are based on the published study in China, and the rasburicase prevention or treatment failure rate was either calculated based on the risk ratio or directly from the clinical study among non-Chinese pediatric patients. Another study limitation was the lack of utility data for pediatric patients with TLS and without TLS. Thus, the utility scores of pediatric cancer survivors were used as an alternative. Conclusion: Rasburicase is estimated to be a cost-effective alternative to SOC in the prevention and treatment of TLS among Chinese pediatric patients with AML, ALL, and NHL.

Decreasing Inappropriate Use of Rasburicase to Promote Cost-Effective Care.

BACKGROUND: Rasburicase is a recommended treatment of tumor lysis syndrome and patients at high-risk for developing tumor lysis syndrome. Unfortunately, it is expensive, and unnecessary use raises costs of care. METHODS: Plan, Do, Study, Act methodology was used to decrease the inappropriate use of rasburicase. In the Plan phase, a multidisciplinary quality improvement team reviewed the rasburicase ordering process and its prescription patterns at Parkland Health and Hospital System between October 2015 and September 2017 to determine appropriate interventions for improvement. In the Do phase, interventions were deployed to improve rasburicase prescriptions. In the Study phase, the team reviewed the rasburicase orders and appropriateness from February 2018 to October 2018. During the Act phase, the interventions were found to be successful, and the process changes were solidified. RESULTS: At baseline, 65 doses of rasburicase were administered during the 2-year baseline period, 21 of these (32.3%) were inappropriate. Review of the ordering process identified pitfalls: one-click ready-to-sign order, fixed default dose, no hard-stop alert requiring physicians to review and confirm appropriate indications, and lack of secondary pharmacy review. We aimed to reduce the percentage of inappropriate rasburicase orders from a baseline of 32.3% to 10% over 3 months. In February 2018, we implemented the interventions, which resulted in reduction in inappropriate rasburicase use, with only a single inappropriate order placed in 7 months postintervention. CONCLUSION: A multidisciplinary approach and classic quality improvement methodology enabled us to reduce inappropriate rasburicase use. Straightforward electronic medical record interventions and secondary pharmacy review are effective in addressing overuse.

The value of fixed rasburicase dosing versus weight-based dosing in the treatment and prevention of tumor lysis syndrome.

BACKGROUND: Rasburicase is a recombinant urate oxidase enzyme used for the treatment and prevention of tumor lysis syndrome. Our objective was to assess the efficacy of indication-based, low-dose rasburicase administration compared to the Food and Drug Administration-approved weight-based dosing. METHODS: This was a retrospective cohort study utilizing data from a tertiary medical center including patients admitted from 2012 to 2016, who received at least one dose of rasburicase. The primary outcome was achieving a uric acid level less than 7.5 mg/dl after a single dose of rasburicase in the preprotocol (Food and Drug Administration-approved weight-based dosing) and postprotocol (indication-based, low-dose) groups. Secondary outcomes included the change in uric acid levels between the pre- and postprotocol groups, adherence to the new institutional protocol, need for repeat rasburicase doses, and a cost analysis. RESULTS: Sixty-four patients received at least one dose of rasburicase between 1 January 2012 and 1 December 2016. Twenty-seven (79.4%) doses in the preprotocol group and 28 (82.4%) doses in the postprotocol group successfully achieved a uric acid level less than 7.5 mg/dl after a single dose of rasburicase (p=1.000). The average total monthly cost of rasburicase was reduced by 59.9% after adoption of the new protocol. CONCLUSIONS: Indication-based, low-dose rasburicase displayed significantly more value when compared to weight-based dosing as shown by achieving cost savings without compromising clinical efficacy.

Risk-based management strategy and outcomes of tumor lysis syndrome in children with leukemia/lymphoma: Analysis from a resource-limited setting.

BACKGROUND: Data from low- and middle-income countries on tumor lysis syndrome (TLS) in the pediatric population are limited. This study aims to analyze the clinical and biochemical characteristics and treatment outcomes of TLS in children with leukemia/lymphomas in a resource-limited setting. PROCEDURE: Children with intermediate risk (IRD) and high risk (HRD) for developing TLS were retrospectively studied at a tertiary cancer center in India. RESULTS: Over a three-year period, 224 children with acute leukemia/lymphoma having IRD (21.8%, n = 49) and HRD (78.1%, n = 175) were identified. TLS developed in 53.6% (n = 120) cases, of which 75% (n = 90) had laboratory TLS alone. Thirteen children had clinical TLS (C-TLS) at presentation while 17 patients progressed to develop C-TLS. TLS developed in 51% (n = 25) and 54.5% (n = 95) of children with IRD and HRD, respectively. Rasburicase was used in 8.5% (n = 19) cases and five children required hemodialysis. Two children (0.8%) expired during the course of TLS management. Multivariate analysis identified the presence of hyperuricemia as the single significant risk factor for developing TLS. When children in whom a 25% change in biochemical values from the baseline that falls within the normal range were excluded, 21.4% (48/224) cases were identified to have clinically relevant TLS (8% in IRD and 25% in HRD). CONCLUSION: With hydration, supportive care and judicious use of rasburicase, it is feasible to manage TLS efficiently in resource-limited settings. A modification of the TLS definition criteria would help to identify clinically relevant TLS.

Comparison of fixed versus traditional weight-based dosing of rasburicase in a pediatric population.

BACKGROUND: The American Society of Clinical Oncology guidelines recommend rasburicase for the treatment of pediatric patients with hyperuricemia at risk of tumor lysis syndrome (TLS) using a weight-based dose of 0.1-0.2 mg/kg once daily for 1-7 days. However, there has been a trend in practice due to recent data showing benefit using a fixed-dose approach. The purpose of this study was to evaluate the efficacy and safety between fixed and weight-based dosing of rasburicase in a pediatric population. PROCEDURE: This was a retrospective chart review of 48 patients from January 1, 2007 to August 31, 2016 at Children's National Health System. Patients less than 18 years old with a documented diagnosis of a malignancy and baseline uric acid level were included; patients less than 30 kg at the time of rasburicase administration were excluded. RESULTS: The primary endpoint of this study was the treatment success of normalization of uric acid level (<5 mg/dl) within 24 hr of rasburicase administration. Eighty-three percent of patients had success with normalization of uric acid post rasburicase dose. Eighty-five percent of patients had success in the weight-based group compared to eighty-one percent in the fixed-dose group (P = 0.715). Mean percent reduction of uric acid at 24 hr was relatively similar between both groups (94% vs. 89%). CONCLUSION: Our results suggest that a fixed-dose strategy of rasburicase is both safe and effective in reducing uric acid levels in the pediatric patient population. A fixed dose of rasburicase 6 mg is a cost-effective treatment option for TLS.

A Clinical and Economic Comparison of Rasburicase and Allopurinol in the Treatment of Patients With Clinical or Laboratory Tumor Lysis Syndrome.

BACKGROUND: The aim of the study was to compare reductions in uric acid (UA), length of stay (LOS), and hospitalization costs in patients with tumor lysis syndrome (TLS) treated with rasburicase or allopurinol. PATIENTS AND METHODS: This retrospective study of administrative data included hospitalized pediatric and adult patients who had clinical or laboratory TLS and received rasburicase or allopurinol. Each rasburicase-treated patient was propensity score-matched with 4 allopurinol-treated patients. Mean changes in UA within ≤ 2 days of treatment initiation were determined. Economic outcomes included mean number of days in the intensive care unit (ICU), total LOS, costs/hospitalization, and costs/percentage change in UA. RESULTS: Twenty-six rasburicase-treated patients were matched with 104 allopurinol-treated patients. Reduction in plasma UA was 5.3 mg/dL greater for patients treated with rasburicase than for patients treated with allopurinol (P < .0001). Length of ICU stay was 2.5 days less for patients treated with rasburicase than for patients treated with allopurinol (P < .0001), and total LOS was 5 days less for patients treated with rasburicase than for patients treated with allopurinol (P = .02). Total costs per patient were $20,038 lower for patients treated with rasburicase than for patients treated with allopurinol (P < .02). Cost per percentage UA reduction was also lower for patients treated with rasburicase versus patients treated with allopurinol ($3899 vs. $16,894; P < .001). CONCLUSION: In this analysis of TLS patients who received care in real-world settings, rasburicase versus allopurinol was significantly more effective in treating hyperuricemia and was associated with significantly shorter ICU and overall hospital stays and lower total inpatient costs.

Efficacy and cost of single-dose rasburicase in prevention and treatment of adult tumour lysis syndrome: a meta-analysis.

WHAT IS KNOWN AND OBJECTIVE: Single-dose rasburicase for the treatment and prevention of hyperuricaemia in adult and paediatric patients with cancer at high risk of tumour lysis syndrome (TLS) has been widely adopted in pharmacy practice as unlabelled use with limited clinical evidence. This meta-analysis study evaluated the efficacy and cost savings of a single-dose rasburicase (SDR) regimen compared with the Food and Drug Administration-approved daily dosing of rasburicase (DDR) for 5 days or the traditional treatment with allopurinol in adult cancer patients with hyperuricaemia or at high risk for TLS. METHODS: Prospective and retrospective studies were retrieved from a systemic search of major electronic data sources. Studies included in the meta-analysis were those with SDR for the prophylaxis of high-risk TLS or treatment of hyperuricaemia in adult patients with cancer. The results of response rate and controlling of time-dependent plasma uric acid (UA) reduction were pooled and compared with the results from patients treated with DDR for 5 days or patients treated with allopurinol. A cost analysis was performed to analyse the treatment costs for adults with hyperuricaemia or at high risk for TLS. RESULTS AND DISCUSSION: Ten studies (eight retrospective and two prospective) evaluated the SDR response rate and plasma UA level reduction over time. The pooled total number of patients treated with SDR (from 0·05 mg/kg to 0·20 mg/kg) was 269. The pooled response rate of the SDR arm was not significantly different than that of DDR (0·2 mg/kg) arm (88·15% vs. 90·18%, P = 0·542), but significantly stronger than that of allopurinol (300 mg/day orally days 1 to 5) arm (response rate: 88·15% vs. 66%, P < 0·0005). Pooled SDR group efficiently controlled the plasma uric acid (UA) level below 4·5 mg/dL over 24 h, 48 h and 72 h, whereas DDR reduced plasma UA levels to hypouricaemia level (<2 mg/dl). In addition, cost analysis demonstrated that standard-dose SDR (≥6 mg) has non-inferior clinical benefit and significant cost savings compared with the DDR regimen. WHAT IS NEW AND CONCLUSION: Single-dose rasburicase (SDR) for adult cancer patients with hyperuricaemia or at high risk for TLS demonstrated better response rate and stronger control of uric acid level compared with allopurinol. SDR response rate was not inferior to that of DDR, and the standard-dose SDR generates more cost savings compared with the DDR. It suggests that the single-dose rasburicase is clinically effective and cost efficient for the prophylaxis of high-risk TLS and the treatment of hyperuricaemia in adult patients with cancer. Additional randomized control studies are needed to confirm the findings of this meta-analysis study.

Economic implications of rasburicase treatment in adult patients with tumour lysis syndrome.

BACKGROUND: Rasburicase is a recombinant urate-oxidase enzyme used to reduce high levels of plasma uric acid (PUA) resulting from tumour lysis syndrome (TLS). Rasburicase reduces PUA levels within 4 hours of administration, thereby minimizing the risk of serious complications from TLS. Treatment pattern analyses indicate rasburicase is often used in combination with allopurinol; however, no studies have evaluated the clinical and economic consequences of this pattern of care. The purpose of this study was to compare hospitalization costs, overall length of stay (LOS), and critical-care LOS in patients receiving rasburicase with or without allopurinol. METHODS: Hospital claims data from the Premier Perspective Database™ were used to conduct this retrospective analysis. Patients in the Premier hospital database who were administered rasburicase or combination therapy (rasburicase + allopurinol) within 2 days of hospital admission were eligible for study inclusion. Patients were excluded if they were <18 years of age or received haemodialysis (or any other renal replacement therapy support) on admission. Rasburicase patients were propensity-score-matched to combination therapy patients based on gender, race, hospital type (urban/rural, teaching), provider type, payer type, admission source, use of electrolyte modification therapy, critical-care admission and presence of a cancer diagnosis. Differences in healthcare costs, overall LOS and critical-care LOS were assessed using γ-distributed generalized linear models with a log-link function. RESULTS: The study population comprised 66 patients receiving rasburicase monotherapy matched to 66 patients receiving combination therapy. Mean age was 62.9 years, and 29% were female. Patients initiated on combination therapy had a shorter mean duration of rasburicase administration than patients initiated on monotherapy (2.1 vs 2.7 days) [p = 0.0059]. Additionally, rasburicase monotherapy incurred an average total cost of $US35 843 per hospitalization, compared with $US46 672 for those receiving combination therapy (p = 0.0820). Rasburicase monotherapy patients also had a shorter mean overall LOS (10.0 days vs 15.4 days; p = 0.0067). The mean critical-care LOS was similar in both cohorts (2.4 days rasburicase vs 2.9 days combination therapy; p = 0.3389). CONCLUSION: Examination of claims data showed that combination therapy (rasburicase + allopurinol) trended toward higher total hospitalization costs than rasburicase monotherapy. In addition, combination therapy was associated with significantly longer overall LOS compared with upfront rasburicase monotherapy in patients at risk for developing TLS.

Evaluation of a low, weight-based dose of rasburicase in adult patients for the treatment or prophylaxis of tumor lysis syndrome.

PURPOSE: Rasburicase is a recombinant urate oxidase enzyme generally reserved for the treatment or prevention of hyperuricemia in patients that are at high risk of developing tumor lysis syndrome (TLS). The primary objective of this study is to evaluate and characterize the outcomes of patients receiving low dose rasburicase for treatment or prophylaxis of hyperuricemia secondary to TLS. PATIENTS/METHODS: A retrospective chart review between April 1, 2007 and September 31, 2008 was completed. All adult patients who received a dose of 0.05mg/kg with either a leukemia or lymphoma diagnosis in addition to at least two TLS risk factors: WBC ≥ 50 × 109/L, LDH 2 × ULN, uric acid ≥ 8 mg/dl, SCr ≥ 1.5 mg/dl were included. Forty-eight patients received rasburicase for prophylaxis (n = 18) or treatment (n = 30) of TLS. RESULTS: Forty patients achieved and maintained a uric acid less than 8 mg/dL, 24 h after receipt of a single dose of rasburicase without the requirement for renal replacement therapy. A statistically significant decrease in UA was achieved in all patients when compared to baseline (p < 0.001). Cost analysis revealed a $ 1.96 million (96%) direct cost savings for the 48 patients in this study when compared to the cost of manufacturer's dosing recommendation. CONCLUSIONS: Low dose rasburicase was efficacious and cost effective for both prophylaxis and treatment of TLS. Administration of a single dose of 0.05mg/kg of rasburicase was sufficient in correcting uric acid levels for most patients.

Economic comparison of rasburicase and allopurinol for treatment of tumor lysis syndrome in pediatric patients.

PURPOSE: Economic outcomes of rasburicase and allopurinol for treatment of tumor lysis syndrome (TLS) in pediatric patients were compared. METHODS: Claims data from a large hospital database were used to conduct the analysis. Pediatric patients diagnosed with TLS and administered rasburicase or allopurinol within two days of hospital admission were eligible for inclusion. Patients were excluded if they were age ≥18 years or received hemodialysis on admission. Patients receiving rasburicase were propensity score matched to allopurinol-treated patients based on sex, race, hospital type, provider type, payer type, admission source, use of electrolyte modification therapy, and comorbid diagnoses. Differences in health care costs, length of stay (LOS), and duration of subsequent critical care were assessed using γ-distributed generalized linear models with a log-link function. Results A total of 63 allopurinol-treated and 63 rasburicase-treated patients were matched in the analysis. The mean age of patients was 7.4 years, and girls comprised 27% of the sample. Rasburicase-treated patients incurred a mean cost of $30,470 per hospitalization, compared with $35,165 for allopurinol-treated patients (p = 0.427). Duration of critical care was significantly shorter for rasburicase-treated patients (1.4 days versus 2.5 days for allopurinol-treated patients, p = 0.0001); however, mean LOS did not statistically differ between groups, averaging 13.8 days for patients treated with rasburicase and 14.9 days for the allopurinol-treated group. CONCLUSION: Examination of claims from a large hospital database showed that treatment with rasburicase, compared with allopurinol, was associated with a significant reduction in critical care days but not with a significant difference in mean LOS or total cost.

Single-dose rasburicase for tumour lysis syndrome in adults: weight-based approach.

BACKGROUND: The optimal rasburicase dose for adult patients has not been determined. OBJECTIVE: To retrospectively examine use of rasburicase in our centre and to evaluate the effect of a single dose of rasburicase on urate and serum creatinine levels in our adult patients. METHOD: A retrospective chart review was conducted of all adult patients who received rasburicase for treatment of tumour lysis syndrome-associated hyperuricaemia at our academic, urban medical centre from July 2002 to October 2006. RESULT: Twenty-one patients received rasburicase with an average first dose of 0.15 +/- 0.03 mg/kg. The drug dosing was calculated based on the patients' ideal body weight (IBW) or adjusted body weight (aBW) for those who were more than 30% above their IBW. Patients experienced a mean serum urate reduction of 89.7 +/- 9.0% from the baseline through the first 24 h after a single rasburicase dose (11.4 +/- 4.5 mg/dL vs. 1.4 +/- 1.4 mg/dL, respectively, P < 0.001). The urate levels remained within normal limits (<8 mg/dL) in all the patients for 48 h after a single dose of rasburicase. The major limitation of our study is that in 18 of 21 patients we lacked adequate documentation to ascertain that the blood samples sent for urate analysis after drug administration were handled according to the manufacturer's recommendations. However, in this small group of patients, we observed that the effect of rasburicase on serum urate was similar to the total study population. The effect was sustained for 48 h after a single dose. Serum creatinine levels at 24-72 h after the single rasburicase dose were not significantly different from baseline (1.8 mg/dL vs. 2.3 mg/dL, respectively, P = 0.14). CONCLUSION: Rasburicase is an effective treatment for patients with hyperuricaemia and may aid in the prevention of hyperuricaemia-associated nephrotoxicity. From our experience, a single dose of 0.15 mg/kg (IBW or aBW) of rasburicase appears to effectively decrease and maintain urate levels within normal limits for 48 h.

Rasburicase: future directions in tumor lysis management.

Acute tumor lysis syndrome (TLS) is an oncologic emergency resulting in several metabolic derangements. Hyperuricemia and its associated complications are the most frequent manifestations of TLS. Crucial to the management is the prompt initiation of a hypouricemic agent such as rasburicase. An established dose of 0.2 mg/kg of rasburicase is effective at decreasing uric acid levels significantly in 4 h of administration and to undetectable levels in 48 h of initiation. The mean uric acid AUC is significantly lower for patients treated with rasburicase when compared to those receiving allopurinol. Rasburicase has demonstrated excellent tolerability and is potentially cost-effective in patients at high risk for TLS. Rasburicase is a safe and effective hypouricemic agent for both adults and children at high risk for TLS and for this reason should be considered the uricolytic agent of choice in these patients.

Rasburicase: a new approach for preventing and/or treating tumor lysis syndrome.

Tumor lysis syndrome (TLS) is an oncologic emergency requiring prompt attention to the management of potentially life-threatening metabolic derangements. Hyperuricaemia is one of the prominent features of TLS which, if not adequately prevented or treated, may lead to renal failure, requiring dialysis. Conventional management of hyperuricaemia involved the use of aggressive hydration, urinary alkalinization and allopurinol. Despite these measures, as many as 14.1% of high-risk patients may still develop renal failure. With the advent of newer agents such as rasburicase, the paradigm of TLS management has shifted towards risk stratification and the use of rasburicase in conjunction with hydration in patients at high risk for TLS. The advantage of rasburicase over allopurinol is its rapid onset of action, lack of need for urine alkalinization, which may worsen hyperphosphataemia and a satisfactory safety profile. Overall, rasburicase offers a safe and more effective alternative to allopurinol in patients at highest risk for TLS. Some of the unanswered questions requiring further investigation with regard to rasburicase use include the optimal number of doses needed, optimal dose based on uric acid levels and tumor burden, dosing in obese patients and maximum dose.

Managing malignancy-associated hyperuricemia with rasburicase.

Along with hydration and urinary alkalinization, allopurinol has been the standard agent for the management of hyperuricemia in patients with a high tumor burden who are at risk for tumor lysis syndrome. However, this agent often fails to prevent and treat this complication effectively. Rasburicase, a recombinant urate oxidase, acts at the end of the purine catabolic pathway and, therefore, does not induce accumulation of xanthine or hypoxanthine, which can precipitate in the kidneys and lead to impaired renal function. Rasburicase may represent an effective alternative to allopurinol in rapidly reducing uric acid levels, improving patients' electrolyte status, and reversing renal insufficiency. The drug initially was studied in pediatric patients with acute lymphoblastic leukemia and aggressive non-Hodgkin lymphoma; data may suggest comparable benefit in adults with similar lymphoid malignancies. Current and future trials will evaluate alternate doses and schedules of rasburicase to maintain its efficacy while reducing its cost.

Role of i.v. allopurinol and rasburicase in tumor lysis syndrome.

The role of i.v. allopurinol and rasburicase in tumor lysis syndrome (TLS) is described. The current standard management for TLS consists of oral allopurinol in conjunction with i.v. hydration with or without alkalinization. Despite this standard prophylactic regimen, some high-risk patients may still develop urate nephropathy from TLS. Recently, i.v. allopurinol and rasburicase became available for the management of TLS. Available data on i.v. allopurinol indicate that the administration schedule and the adverse-effect profile will be similar to the oral formulation. The primary advantage of i.v. allopurinol is the flexibility of administration for patients who cannot take anything by mouth, since there are no data indicating the superiority of the i.v. to the oral product. Rasburicase is the first agent that will oxidize uric acid to allantoin, a metabolite with 5-10-fold greater solubility than uric acid, and reduces serum uric acid (SUA) levels within four hours of administration. Rasburicase is considerably more expensive than standard management strategies and should be reserved for patients with either renal dysfunction, significant elevations in SUA values, or large tumor burdens. Preliminary evidence indicates that rasburicase offers cost savings in the treatment of TLS and is cost-effective as a strategy for preventing TLS for many cancer patients. Both i.v. allopurinol and rasburicase offer additional flexibility in the management of TLS and may allow for further avoidance of the consequences of inadequate management of this syndrome.