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Howard SC, Avagyan A, Workeneh B, Pui CH. Tumour lysis syndrome. Nat Rev Dis Primers 2024; 10:58. [PMID: 39174582 DOI: 10.1038/s41572-024-00542-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 07/18/2024] [Indexed: 08/24/2024]
Abstract
Tumour lysis syndrome (TLS) represents a critical oncological emergency characterized by extensive tumour cell breakdown, leading to the swift release of intracellular contents into the systemic circulation, outpacing homeostatic mechanisms. This process results in hyperuricaemia (a by-product of intracellular DNA release), hyperkalaemia, hyperphosphataemia, hypocalcaemia and the accumulation of xanthine. These electrolyte and metabolic imbalances pose a significant risk of acute kidney injury, cardiac arrhythmias, seizures, multiorgan failure and, rarely, death. While TLS can occur spontaneously, it usually arises shortly after the initiation of effective treatment, particularly in patients with a large cancer cell mass (defined as ≥500 g or ≥300 g/m2 of body surface area in children). To prevent TLS, close monitoring and hydration to improve renal perfusion and urine output and to minimize uric acid or calcium phosphate precipitation in renal tubules are essential. Intervention is based on the risk of a patient of having TLS and can include rasburicase and allopurinol. Xanthine, typically enzymatically converted to uric acid, can accumulate when xanthine oxidases, such as allopurinol, are administered during TLS management. Whether measurement of xanthine is clinically useful to optimize the use of allopurinol or rasburicase remains to be determined.
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Affiliation(s)
- Scott C Howard
- Resonance, Memphis, TN, USA.
- Yeolyan Center for Hematology and Oncology, Yerevan, Armenia.
- Sant Joan de Déu Hospital Barcelona, Barcelona, Spain.
| | - Anna Avagyan
- Yeolyan Center for Hematology and Oncology, Yerevan, Armenia
| | - Biruh Workeneh
- University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Ching-Hon Pui
- Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN, USA.
- Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN, USA.
- Department of Global Paediatric Medicine, St. Jude Children's Research Hospital, Memphis, TN, USA.
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Gilmore S, Carroll M, Koselke E, Hough S. Rasburicase dose optimization for tumor lysis syndrome management in a network of community oncology practices. J Oncol Pharm Pract 2024; 30:867-872. [PMID: 37563922 DOI: 10.1177/10781552231190005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/12/2023]
Abstract
INTRODUCTION Single, fixed-dose rasburicase administration has been evaluated as an effective strategy in the management of hyperuricemia in the hospital setting, but this has not yet been described within ambulatory community oncology practices. The objective of this study is to evaluate and optimize the dosing strategy for rasburicase in the management of tumor lysis syndrome (TLS)-associated hyperuricemia in The US Oncology Network (The Network). METHODS A network-wide guideline was revised to standardize rasburicase dosing from a previous recommended fixed doses of 4.5 or 7.5 mg to either 3 or 6 mg for outpatient rasburicase use in management and prevention of TLS. The primary outcome evaluated mean dose of rasburicase among all patients before and after guideline revision. A retrospective chart review evaluated secondary endpoints. RESULTS The primary analysis included 291 patients (128 pre-revised and 163 post-revised guideline implementation). The primary outcome, mean rasburicase dose, was reduced in the post-revision compared to the pre-revision population (mean 6.2 mg pre vs. 4.5 mg post, p < 0.00001) resulting in a reduced cost per rasburicase dose of $974. Fifty patients were included for the secondary analysis. Guideline concordance was identified in 12 (48%) and 16 patients (64%), and uric acid <8 mg/dL post-rasburicase administration occurred in 14 (56%) and 16 patients (64%) before and after guideline revision, respectively. CONCLUSIONS Guideline revision and electronic health record modification resulted in a 27% reduction in the mean rasburicase dose and a 50% reduction in repeat rasburicase dosing without a negative impact on clinical efficacy.
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Affiliation(s)
- Steven Gilmore
- The US Oncology Network, McKesson Specialty Health, The Woodlands, TX, USA
| | - Melissa Carroll
- The US Oncology Network, McKesson Specialty Health, The Woodlands, TX, USA
| | - Elizabeth Koselke
- The US Oncology Network, McKesson Specialty Health, The Woodlands, TX, USA
| | - Shannon Hough
- The US Oncology Network, McKesson Specialty Health, The Woodlands, TX, USA
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Latcha S, Shah CV. Rescue Therapies for AKI in Onconephrology: Rasburicase and Glucarpidase. Semin Nephrol 2023; 42:151342. [PMID: 37167817 DOI: 10.1016/j.semnephrol.2023.151342] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/13/2023]
Abstract
Tumor lysis syndrome (TLS) and high-dose methotrexate (HD MTX) toxicity can present with potentially severe complications, including acute kidney injury, in patients with malignancy. Guidelines for using rasburicase and glucarpidase as rescue therapies for TLS and HD MTX toxicity, respectively, are widely used by clinicians intending to mitigate organ toxicity and decrease morbidity and mortality as a consequence of cancer therapy. This review discusses the pathogenesis of TLS and HD MTX-associated toxicity, to understand the mechanism of action of these therapeutic agents and to review the currently available evidence supporting their use.
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Affiliation(s)
- Sheron Latcha
- Renal Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.
| | - Chintan V Shah
- Division of Nephrology, Hypertension and Renal Transplantation, University of Florida College of Medicine, Gainesville, FL
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Review of Hematological and Oncological Emergencies. Adv Emerg Nurs J 2022; 44:84-102. [PMID: 35476684 DOI: 10.1097/tme.0000000000000399] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Patients with hematological malignancies, both treated and untreated, or solid tumors undergoing treatment are at risk of life-threatening complications, which may present in the emergency department (ED). Such emergencies are diverse in etiology and often require prompt treatment. Traditional complications, such as febrile neutropenia, have had recent guideline updates, which incorporate new evidence and a new validated risk stratification tool. In addition, newer approaches to treatment, such as chimeric antigen receptor (CAR) T-cell therapy, are becoming more widely available and have unique associated toxicities. This review discusses the management of the following hematological and oncological emergencies likely to be encountered in the ED: febrile neutropenia, CAR T-cell toxicities, differentiation syndrome, tumor lysis syndrome, hypercalcemia of malignancy, and hyponatremia.
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Marjoncu D, Holman K. The efficacy and cost-impact of rasburicase 3 mg versus 6 mg for the management of tumor lysis syndrome: A multicenter analysis. J Oncol Pharm Pract 2022:10781552221087978. [PMID: 35306913 DOI: 10.1177/10781552221087978] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Purpose: Hyperuricemia is a complication arising from tumor lysis syndrome (TLS). Literature has shown that a single 3 mg dose was just as efficacious as a single 6 mg dose when the uric acid (UA) levels were ≤12 mg/dL. Here, we present a multi-center analysis rasburicase utilization and its effect on healthcare costs. Methods: This is a multi-center, retrospective analysis of adult cancer patients who were admitted to Methodist Le Bonheur Healthcare hospitals and received rasburicase from February 2020 to February 2021. The primary endpoint was to test whether rasburicase 3 mg had similar rates of uric acid normalization (defined as uric acid ≤7.5 mg/dL) within 24 h as a dose of 6 mg. Results: Seventy-nine patients were included in the study. While the baseline uric acid was lower in the 3 mg arm compared to the 6 mg arms, there was no difference in the uric acid normalization at 24 h between the 3 mg arm (95%) and 6 mg arm (82%) (p = 0.134). A cost-savings of over $300,000 annually can be achieved with the proposed protocol. Conclusion: A single, fixed rasburicase dose of 3 mg was effective in normalizing uric acid levels within 24 h, and is associated with significant cost-savings.
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Affiliation(s)
- Dennis Marjoncu
- Department of Pharmacy, 5416Methodist Le Bonheur Healthcare, Memphis, TN, United States
| | - Kori Holman
- Department of Pharmacy, 5416Methodist Le Bonheur Healthcare, Memphis, TN, United States
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Vachhani P, Baron J, Freyer CW, Miller A, Wetzler M, Thompson JE, Griffiths EA, Wang ES. A phase 2 trial of single low doses of rasburicase for treatment of hyperuricemia in adult patients with acute leukemia. Leuk Res 2021; 107:106588. [PMID: 33957371 DOI: 10.1016/j.leukres.2021.106588] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2021] [Revised: 03/22/2021] [Accepted: 03/26/2021] [Indexed: 11/26/2022]
Abstract
BACKGROUND Rasburicase can markedly and rapidly decrease uric acid (UA) levels, thereby preventing and treating tumor lysis syndrome. However, rasburicase is expensive, especially when used as per the manufacturer's recommended dosage of 0.2 mg/kg/day for up to 5 days. Numerous reports have shown that lower, and even single doses are effective in lowering UA levels but prospective randomized studies comparing low doses have not been performed. OBJECTIVES To prospectively determine the efficacy and safety of two single low doses of rasburicase in adult patients (pts) with acute leukemia and elevated plasma UA. METHODS Eligible pts aged ≥ 18 years old with acute leukemia and UA ≥ 7.5 mg/dL were randomized to receive an initial single dose of rasburicase 1.5 mg (Arm A) or 3 mg (Arm B) on day 1 in an unblinded fashion. All pts received allopurinol 300 mg daily on days 1-6. RESULTS Twenty-four pts (median age 69 years; 14 males and 10 females) were enrolled in this phase 2 study (12 on each arm). Twenty pts had acute myeloid leukemia while 3 had acute lymphoblastic leukemia, and 1 had acute promyelocytic leukemia. Median initial UA level was 9.8 mg/dL. Eighty-three percent of pts in both arms achieved UA < 7.5 mg/dL by 24 h after therapy. Five pts (21 %; 2 from Arm A and 3 from Arm B) required additional doses of rasburicase. The majority (23/24) of pts achieved UA goals after 1-2 doses of rasburicase. None had worsening renal function. Both doses were well tolerated, and no treatment related adverse events were reported. CONCLUSIONS Single doses of rasburicase (as low as 1.5-3 mg) used in addition to allopurinol were well tolerated and highly efficacious (83 % response rate) in decreasing UA levels within 24 h of administration in adult acute leukemia pts with hyperuricemia.
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Affiliation(s)
- Pankit Vachhani
- Division of Hematology and Oncology, Department of Medicine, University of Alabama at Birmingham (UAB), Birmingham, AL, USA.
| | - Jeffrey Baron
- Department of Pharmacy, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA
| | - Craig W Freyer
- Department of Pharmacy, Hospital of the University of Pennsylvania, Philadelphia, PA, USA
| | - Austin Miller
- Department of Biostatistics & Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA
| | - Meir Wetzler
- Section of Leukemia, Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA
| | - James E Thompson
- Section of Leukemia, Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA
| | - Elizabeth A Griffiths
- Section of Leukemia, Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA
| | - Eunice S Wang
- Section of Leukemia, Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA
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Gupta G, Seth T, Garg V, Juneja R, Mahapatra M, Datta SK, Upadhyay AD, Saxena R. Efficacy of Single Low-Dose Rasburicase in Management of Tumor Lysis Syndrome in Leukemia and Lymphoma Patients. CLINICAL LYMPHOMA, MYELOMA & LEUKEMIA 2021; 21:e99-e104. [PMID: 33039358 DOI: 10.1016/j.clml.2020.08.024] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/15/2020] [Revised: 08/28/2020] [Accepted: 08/31/2020] [Indexed: 10/23/2022]
Abstract
BACKGROUND Tumor lysis syndrome (TLS) is a metabolic emergency in hematology patients. The recommended dose of rasburicase for the management of TLS is 0.2 mg/kg per day for 5 days, which is cost prohibitive for many patients. We sought to determine the efficacy of single low-dose rasburicase in the prevention and treatment of hyperuricemia in TLS. PATIENTS AND METHODS We planned a prospective study for the safety and efficacy of fixed (weight based) dose of rasburicase to manage TLS. Patients diagnosed with leukemia/lymphoma with laboratory or clinically confirmed TLS or presence of ≥ 2 high-risk factors and serum uric acid > 7.5 mg/dL were included. The primary endpoint was uric acid normalization (< 7.5 mg/dL) within 24 hours of rasburicase administration. RESULTS Fifty-five patients were recruited for this study. Pediatric patients (< 18 years) accounted for 43.6% of cases. Rasburicase was provided prophylactically to 43 patients (78.2%) and for treating TLS to 12 (21.8%). Mean ± standard deviation serum uric acid at baseline and 24 hours was 9.2 ± 1.8 mg/dL and 3.2 ± 2.1 mg/dL, respectively. There was significant reduction in the serum uric acid and creatinine (P < .001) within 24 hours of rasburicase administration. The response was maintained up to 72 hours. A single dose of rasburicase was effective in 94.5% of patients. Single low-dose rasburicase led to 95% direct cost savings compared to the recommended dose. CONCLUSION Single-dose rasburicase with frequent laboratory monitoring is effective in the management of TLS and offers significant cost reductions.
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Affiliation(s)
- Gopila Gupta
- Department of Haematology, All India Institute of Medical Sciences, New Delhi, India.
| | - Tulika Seth
- Department of Haematology, All India Institute of Medical Sciences, New Delhi, India
| | - Vikas Garg
- Department of Medical Oncology, All India Institute of Medical Sciences, New Delhi, India
| | - Richa Juneja
- Department of Haematology, All India Institute of Medical Sciences, New Delhi, India
| | - Manoranjan Mahapatra
- Department of Haematology, All India Institute of Medical Sciences, New Delhi, India
| | - Sudip Kumar Datta
- Department of Laboratory Medicine, All India Institute of Medical Sciences, New Delhi, India
| | - Ashish Datt Upadhyay
- Department of Biostatistics, All India Institute of Medical Sciences, New Delhi, India
| | - Renu Saxena
- Department of Haematology, All India Institute of Medical Sciences, New Delhi, India
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Wesemüller W, Taverna C. Spontaneous Tumor Lysis Syndrome. Case Rep Oncol 2020; 13:1116-1124. [PMID: 33082757 PMCID: PMC7549013 DOI: 10.1159/000509643] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2020] [Accepted: 06/23/2020] [Indexed: 11/19/2022] Open
Abstract
Tumor lysis syndrome (TLS) is a hemato-oncological emergency characterized by metabolic and electrolyte imbalances which are associated with disintegrating tumor cells. The syndrome is frequently observed when starting cytotoxic treatment of hematological malignancies, while the incidence of spontaneous tumor lysis prior to the start of tumor therapy is rare. Here, we present a case of spontaneous TLS in a male patient who was referred with unspecific symptoms and suspected metastatic malignancy. He developed acute renal failure before the diagnosis of a high-grade B-cell lymphoma (double hit lymphoma) and start of therapy. Although the course of TLS would have required intensive care, the patient rejected such treatment for personal reasons and died soon after the discontinuation of therapy. The case emphasizes the life-saving relevance of early detection and appropriate treatment of TLS. It also demonstrates the importance of actively screening for TLS, primarily in patients with malignant diseases and high tumor load, even if they are not receiving cytotoxic therapy.
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Abousaud MI, Rush MC, Rockey M. Assessment of rasburicase utilization for tumor lysis syndrome management in pediatric and adult patients in the inpatient and outpatient settings. J Oncol Pharm Pract 2020; 27:1165-1171. [PMID: 32727320 DOI: 10.1177/1078155220945368] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
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.
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Affiliation(s)
- Marin I Abousaud
- Department of Pharmacy, 528756Wake Forest Baptist Health, Winston-Salem, NC, USA
| | - Marie C Rush
- Department of Pharmacy, 528756Wake Forest Baptist Health, Winston-Salem, NC, USA
| | - Michelle Rockey
- Department of Pharmacy, 528756Wake Forest Baptist Health, Winston-Salem, NC, USA
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McKenna S, Cheung A, Wolfe A, Coleman BL, Detsky ME, Munshi L, Maze D, Burry L. Clinical Interventions to Prevent Tumour Lysis Syndrome in Hematologic Malignancy: A Multisite Retrospective Chart Review. Can J Hosp Pharm 2019; 72:435-445. [PMID: 31853144 PMCID: PMC6910844] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/10/2023]
Abstract
BACKGROUND Tumour lysis syndrome (TLS) occurs when lysis of malignant cells causes electrolyte disturbances and potentially organ dysfunction. Guidelines recommending preventive therapy according to TLS risk are based on low-quality evidence. OBJECTIVES The primary objective was to characterize utilization of TLS preventive strategies through comprehensive description of current practice. Secondary objectives were to determine TLS incidence, to compare use of preventive strategies among intermediate- and high-risk patients, and to describe TLS treatment strategies. METHODS This retrospective chart review examined data for patients with newly diagnosed hematologic malignancy who were admitted to an oncology centre and/or affiliated intensive care unit between October 2015 and September 2016 in Toronto, Ontario, Canada. RESULTS Fifty-eight patients (29 at intermediate risk, 29 at high risk) were eligible for inclusion. Use of preventive allopurinol, IV bicarbonate, and furosemide was similar between groups. Rasburicase was more frequently used for high-risk patients (3% [1/29] of intermediate-risk patients versus 36% [9/25] of high-risk patients; p = 0.003). In 4 (14%) of the intermediate-risk patients and 2 (8%) of the high-risk patients, TLS developed during the admission. TLS was observed in 10% (1/10) of patients who received preventive rasburicase and 11% (5/44) of those who did not (p > 0.99), and in 9% (4/45) of patients who received preventive IV bicarbonate and 25% (2/8) of those who did not (p = 0.22). Treatment strategies included rasburicase, IV bicarbonate, furosemide, and renal replacement therapy. CONCLUSIONS In this retrospective chart review, rasburicase was more commonly used for high-risk patients, whereas the use of other agents was similar between risk groups. This pattern of use is inconsistent with guidelines, which recommend that all high-risk patients receive rasburicase. There was no difference in TLS incidence between patients who did and did not receive preventive rasburicase or IV bicarbonate. Further prospective studies are needed to inform management of patients with malignancies who are at intermediate or high risk of TLS.
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Affiliation(s)
- Sarah McKenna
- PharmD, ACPR, is with the Department of Pharmacy, Mount Sinai Hospital, Sinai Health System, Toronto, Ontario
| | - Alexandra Cheung
- , BScPhm, PharmD, is with the Department of Pharmacy, Mount Sinai Hospital, Sinai Health System, Toronto, Ontario
| | - Amanda Wolfe
- (formerly Amanda Jacques), BScPharm, ACPR, was, at the time this study was conducted, with the Department of Pharmacy, Princess Margaret Cancer Centre, University Health Network, and the Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario. She is now with the Department of Pharmacy, Bruyère Continuing Care, Ottawa, Ontario
| | - Brenda L Coleman
- PhD, is with Infectious Disease Research, Mount Sinai Hospital, Sinai Health System, and the Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario
| | - Michael E Detsky
- MD, MSHP, FRCPC, is with the Interdepartmental Division of Critical Care, University Health Network/Sinai Health System, and the Interdepartmental Division of Critical Care and Faculty of Medicine, University of Toronto, Toronto, Ontario
| | - Laveena Munshi
- MD, MSc, FRCPC, is with the Interdepartmental Division of Critical Care, University Health Network/Sinai Health System, Toronto, Ontario
| | - Dawn Maze
- MD, MSc, FRCPC, is with the Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, and the Faculty of Medicine, University of Toronto, Toronto, Ontario
| | - Lisa Burry
- PharmD, is with the Department of Pharmacy, Mount Sinai Hospital, Sinai Health System, and the Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario
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Ngo JS, Ho MHM. Evaluation of Rasburicase Use in the Fraser Health Authority: A Retrospective Review. Can J Hosp Pharm 2019; 72:311-319. [PMID: 31452543 PMCID: PMC6699871] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/10/2023]
Abstract
BACKGROUND Rasburicase, a recombinant urate oxidase, is restricted in the Fraser Health Authority (FHA) to the "treatment of acute or at high risk of tumour lysis syndrome [TLS], when other therapeutic options are not suitable". The manufacturer's recommended dosage is 0.2 mg/kg daily for up to 7 days. Given the high cost of this drug, several studies have investigated other strategies and found that a single dose, repeated as needed, is effective in reducing serum uric acid. However, there are currently no guidelines in FHA for the use of rasburicase, which may result in different prescribing practices within the health authority. OBJECTIVES To describe the prescribing of rasburicase in FHA, including indications and doses, and to report the uric acid-lowering effects of rasburicase and any clinical outcomes, such as dialysis or death. METHODS This retrospective descriptive chart review included adult patients receiving care in FHA for whom rasburicase was prescribed between June 1, 2010, and November 30, 2016. Descriptive statistics were used to summarize patient characteristics and results. RESULTS The prescribing practices for rasburicase in this health authority were largely inconsistent, but the most common dose administered was 3 mg (8/12 [67%] among those receiving rasburicase for prophylaxis and 9/32 [28%] among those receiving rasburicase for treatment; combined total 17/44 or 39%). Regardless of dose, rasburicase reduced serum uric acid levels to less than 476 μmol/L and decreased the risk of TLS. CONCLUSIONS Having a uniform approach-involving a single dose that can be repeated as needed-for prevention and treatment of elevated serum uric acid levels could result in sufficient reduction of uric acid levels with fewer doses and lower cost. The results of this study support the need for a resource in FHA to guide and standardize the use of rasburicase.
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Affiliation(s)
- Jia Shermaine Ngo
- BScPharm, ACPR, is a Clinical Pharmacist with Vancouver General Hospital, Vancouver, British Columbia BScPharm, ACPR, is a Clinical Pharmacist with Royal Columbian Hospital, New Westminster, British Columbia
| | - Man Hon Mark Ho
- BScPharm, ACPR, is a Clinical Pharmacist with Vancouver General Hospital, Vancouver, British Columbia BScPharm, ACPR, is a Clinical Pharmacist with Royal Columbian Hospital, New Westminster, British Columbia
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Agarwal A, Lakshmaiah KC, Babu KG, Rajeev LK, Loknatha D, Abraham L, Babu MC, Lokesh KN, Rudresha AH. Efficacy of a reduced-dose rasburicase: Single-institution experience in India. Indian J Med Paediatr Oncol 2019. [DOI: 10.4103/ijmpo.ijmpo_189_16] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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Savva DA, Herrera N, Rohatgi R. Comparison of fixed versus traditional weight-based dosing of rasburicase in a pediatric population. Pediatr Blood Cancer 2018; 65:e27236. [PMID: 29905398 DOI: 10.1002/pbc.27236] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2017] [Revised: 04/16/2018] [Accepted: 04/17/2018] [Indexed: 11/08/2022]
Abstract
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.
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Affiliation(s)
- Dimitrios A Savva
- Department of Pharmacy Practice and Science, University of Maryland School of Pharmacy, Baltimore, Maryland
| | - Nicole Herrera
- Children's Research Institute, Children's National Health System, Silver Spring, Maryland
| | - Radha Rohatgi
- Division of Pharmacy Services, Children's National Health System, Washington, District of Columbia
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Nauffal M, Redd R, Ni J, Stone RM, DeAngelo DJ, McDonnell AM. Single 6-mg dose of rasburicase: The experience in a large academic medical center. J Oncol Pharm Pract 2018; 25:1349-1356. [DOI: 10.1177/1078155218791333] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Background Tumor lysis syndrome is an oncologic emergency due to the release of tumor cell contents, leading to metabolic derangements. Rasburicase, a recombinant urate oxidase, catabolizes uric acid. At our institution, we administer a single 6-mg dose of rasburicase to patients who are at risk for tumor lysis syndrome. We aimed to assess the efficacy of single 6-mg dose of rasburicase and explore risk factors associated with rasburicase failure. Methods We report results in 92 adult patients who had a baseline uric acid greater than 7.5 mg/dL and received a single 6-mg dose of rasburicase for the management of tumor lysis syndrome. Responders were defined as those whose uric acid was less than or equal to 7.5 mg/dL within 24–36 h of rasburicase administration. The primary end point was response based on uric acid level. Secondary end points included response to rasburicase in association with lactate dehydrogenase, serum creatinine, calcium, phosphorus, blood pH, and oncologic diagnosis. Results Median age was 65 years and 70% were men. Most patients had leukemia (32%) or lymphoma (40%). Eighty-seven of 92 patients (95%), who received single 6-mg dose of rasburicase, achieved a uric acid less than 7.5 mg/dL within 24–36h of dosing. Body mass index was similar between responders and non-responders: 28.6 kg/m2 vs. 26.6 kg/m2, respectively, p = 0.6. Baseline lactate dehydrogenase levels were similar between the groups: 756 U/L vs. 892 U/L, respectively, p = 0.33. Blood pH values documented within 24 h of first dose of rasburicase were also similar between the two groups (n = 30; 7.33 vs. 7.34 respectively, p = 0.6). However, median baseline uric acid was lower in responders than non-responders: 12.3 mg/dL vs. 17.3 mg/dL, respectively, p = 0.012. Baseline serum creatinine and creatinine clearance were similar between responders and non-responders (2.2 mg/dL vs. 3.95 mg/dL; p = 0.12 and 29 mL/min vs. 16 mL/min; p = 0.11, respectively). Conclusions Higher baseline uric acid levels were observed in patients who did not respond to the first rasburicase dose. In our study, uric acid levels normalized in 95% of patients after a single 6-mg dose of rasburicase indicating that a single 6-mg dose of rasburicase may be sufficient to manage tumor lysis syndrome, for most patients.
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Affiliation(s)
- Mary Nauffal
- Department of Pharmacy Services, Brigham and Women’s Hospital, Boston, MA, USA
| | - Robert Redd
- Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA, USA
| | - Jian Ni
- Department of Pharmacy Services, Brigham and Women’s Hospital, Boston, MA, USA
| | - Richard M Stone
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA
| | - Daniel J DeAngelo
- Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA
| | - Anne M McDonnell
- Department of Pharmacy Services, Brigham and Women’s Hospital, Boston, MA, USA
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Boutin A, Blackman A, O’Sullivan DM, Forcello N. The value of fixed rasburicase dosing versus weight-based dosing in the treatment and prevention of tumor lysis syndrome. J Oncol Pharm Pract 2018; 25:577-583. [DOI: 10.1177/1078155217752075] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
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.
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Abstract
Cancer and its therapies may lead to several metabolic emergencies that emergency providers (EPs) should be well-versed in identifying and managing. With prompt recognition and treatment initiation in the emergency department, lives can be saved and quality of life maintained. Most oncologic metabolic emergencies occur in advanced cancer states, but some follow initiation of treatment or may be the presenting syndrome that leads to the cancer diagnosis. This article reviews the 2 most emergent oncologic metabolic diagnoses: tumor lysis syndrome and hypercalcemia of malignancy. A discussion on associated cancers and conditions, pathogenesis and pathophysiology, and management recommendations is included.
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Affiliation(s)
- Jonathan Wagner
- Department of Emergency Medicine, Keck School of Medicine of the University of Southern California, 1200 North State Street, Room 1011, Los Angeles, CA 90033, USA.
| | - Sanjay Arora
- Department of Emergency Medicine, Keck School of Medicine of the University of Southern California, 1200 North State Street, Room 1011, Los Angeles, CA 90033, USA
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17
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Usami E, Kimura M, Iwai M, Teramachi H, Yoshimura T. Analysis of the incidence of tumor lysis syndrome in patients with hematological malignancies treated with rasburicase. Mol Clin Oncol 2017; 6:955-959. [PMID: 28588796 DOI: 10.3892/mco.2017.1232] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2016] [Accepted: 03/16/2017] [Indexed: 11/05/2022] Open
Abstract
The purpose of this study was to assess the incidence of tumor lysis syndrome (TLS) in patients with hematological malignancies treated with rasburicase, and to evaluate the dose and duration of rasburicase administration. A total of 52 patients were enrolled. The background of the patients, incidence of TLS and laboratory data were retrospectively examined; in addition, the dose and duration of rasburicase administration and the factors affecting the onset of TLS were evaluated and compared among TLS risk categories. During the study period, 2 (3.8%) of the patients developed clinical TLS and 24 (46.2%) developed laboratory TLS (LTLS). Although the LTLS rate was very high, there were no life-threatening cases of TLS. The median daily dose of rasburicase administered to all patients was 7.5 mg/day (interquartile range, 7.5-9.0 mg/day), and the daily weight-based dose was 0.147 mg/kg/day (range, 0.126-0.178 mg/kg/day). The administration duration was 3 days (interquartile range, 3-4 days). Additionally, there was no significant association between TLS risk classification and daily rasburicase administration dose, duration, or post-administration laboratory data. The factors affecting the onset of TLS included serum uric acid level, as well as serum creatinine and phosphate levels. Rasburicase was highly effective in the prevention and management of hyperuricemia, even at a low-dose (7.5 mg/day) and a duration that was 3 days shorter compared with that recommended by the manufacturer. Therefore, clinicians should administer rasburicase based on their clinical judgment, taking into consideration the cost-effectiveness of this therapy.
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Affiliation(s)
- Eiseki Usami
- Department of Pharmacy, Ogaki Municipal Hospital, Ogaki, Gifu 503-8502, Japan
| | - Michio Kimura
- Department of Pharmacy, Ogaki Municipal Hospital, Ogaki, Gifu 503-8502, Japan
| | - Mina Iwai
- Department of Pharmacy, Ogaki Municipal Hospital, Ogaki, Gifu 503-8502, Japan
| | - Hitomi Teramachi
- Laboratory of Clinical Pharmacy, Gifu Pharmaceutical University, Gifu 501-1196, Japan
| | - Tomoaki Yoshimura
- Department of Pharmacy, Ogaki Municipal Hospital, Ogaki, Gifu 503-8502, Japan
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Alakel N, Middeke JM, Schetelig J, Bornhäuser M. Prevention and treatment of tumor lysis syndrome, and the efficacy and role of rasburicase. Onco Targets Ther 2017; 10:597-605. [PMID: 28203093 PMCID: PMC5295804 DOI: 10.2147/ott.s103864] [Citation(s) in RCA: 53] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
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.
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Affiliation(s)
- Nael Alakel
- Department of Internal Medicine I, University Hospital Carl Gustav Carus at the Technische Universitaet Dresden, Dresden
| | - Jan Moritz Middeke
- Department of Internal Medicine I, University Hospital Carl Gustav Carus at the Technische Universitaet Dresden, Dresden
| | - Johannes Schetelig
- Department of Internal Medicine I, University Hospital Carl Gustav Carus at the Technische Universitaet Dresden, Dresden; German Bone Marrow Donor Center DKMS, Tübigen, Germany
| | - Martin Bornhäuser
- Department of Internal Medicine I, University Hospital Carl Gustav Carus at the Technische Universitaet Dresden, Dresden
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Sampling on ice will not yield reliable uric acid monitoring in rasburicase-treated patients. Clin Biochem 2016; 49:1390-1395. [DOI: 10.1016/j.clinbiochem.2016.04.011] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2016] [Revised: 04/22/2016] [Accepted: 04/24/2016] [Indexed: 11/18/2022]
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20
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Yu X, Liu L, Nie X, Li J, Zhang J, Zhao L, Wang X. The optimal single-dose regimen of rasburicase for management of tumour lysis syndrome in children and adults: a systematic review and meta-analysis. J Clin Pharm Ther 2016; 42:18-26. [PMID: 27888526 DOI: 10.1111/jcpt.12479] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2016] [Accepted: 10/21/2016] [Indexed: 11/27/2022]
Affiliation(s)
- X. Yu
- Department of Pharmacy; Beijing Children's Hospital; Capital Medical University; Beijing China
- Department of Pharmacy Administration and Clinical Pharmacy; School of Pharmaceutical Sciences; Peking University Health Science Center; Beijing China
| | - L. Liu
- Department of Pharmacy Administration and Clinical Pharmacy; School of Pharmaceutical Sciences; Peking University Health Science Center; Beijing China
| | - X. Nie
- Department of Pharmacy; Beijing Children's Hospital; Capital Medical University; Beijing China
| | - J. Li
- Department of Pharmacy Administration and Clinical Pharmacy; School of Pharmaceutical Sciences; Peking University Health Science Center; Beijing China
| | - J. Zhang
- Department of Pharmacy Administration and Clinical Pharmacy; School of Pharmaceutical Sciences; Peking University Health Science Center; Beijing China
| | - L. Zhao
- Department of Pharmacy; Beijing Children's Hospital; Capital Medical University; Beijing China
| | - X. Wang
- Department of Pharmacy; Beijing Children's Hospital; Capital Medical University; Beijing China
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Patel KS, Lau JE, Zembillas AS, Gallagher EM. Single 4.5 mg fixed-dose of rasburicase for hyperuricemia associated with tumor lysis syndrome. J Oncol Pharm Pract 2016; 23:333-337. [PMID: 27084514 DOI: 10.1177/1078155216644975] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Rasburicase is a recombinant urate oxidase enzyme administered for treatment of hyperuricemia associated with tumor lysis syndrome. Studies demonstrate effectiveness of single fixed-dose rasburicase as compared to the FDA-approved dose of 0.2 mg/kg intravenously daily for up to five days. Doses in these studies range from 1.5 mg to 7.5 mg. Our study evaluated outcomes in patients who received single 4.5 mg fixed-dose rasburicase. This retrospective, IRB-approved chart review evaluated adult oncology subjects who received fixed-dose rasburicase between January 2007 and April 2014. The primary outcome was percentage of patients with normalization of uric acid (level <8 mg/dL within 24 h) after a single 4.5 mg fixed-dose of rasburicase. Secondary objectives were incidence of initial failure of fixed-dose rasburicase and normalization of uric acid in overweight (body mass index ≥25 kg/m2) versus non-overweight patients. Initial failure was defined as need for additional doses or progression to dialysis within one week of the initial fixed-dose. In the 128 patients included, the mean baseline uric acid level was 14.84 mg/dL. Of the 112 patients with a follow-up uric acid level, 68% achieved normalization within 24 h of rasburicase administration. Thirty-eight patients received additional treatment: 10 received additional dose(s) and 28 underwent dialysis. Normalization of uric acid in overweight versus non-overweight patients was 66% and 73%, respectively. Overall, a single 4.5 mg fixed-dose of rasburicase effectively normalized uric acid in 68% of patients within 24 h. Further studies are needed to determine the optimal single fixed-dose necessary for treatment response across all patients.
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22
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Mirrakhimov AE, Voore P, Khan M, Ali AM. Tumor lysis syndrome: A clinical review. World J Crit Care Med 2015; 4:130-138. [PMID: 25938028 PMCID: PMC4411564 DOI: 10.5492/wjccm.v4.i2.130] [Citation(s) in RCA: 87] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2014] [Revised: 12/20/2014] [Accepted: 02/12/2015] [Indexed: 02/06/2023] Open
Abstract
Tumor lysis syndrome is an oncometabolic emergency resulting from rapid cell death. Tumor lysis syndrome can occur as a consequence of tumor targeted therapy or spontaneously. Clinicians should stratify every hospitalized cancer patient and especially those receiving chemotherapy for the risk of tumor lysis syndrome. Several aspects of prevention include adequate hydration, use of uric acid lowering therapies, use of phosphate binders and minimization of potassium intake. Patients at high risk for the development of tumor lysis syndrome should be monitored in the intensive care unit. Established tumor lysis syndrome should be treated in the intensive care unit by aggressive hydration, possible use of loop diuretics, possible use of phosphate binders, use of uric acid lowering agents and dialysis in refractory cases.
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23
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Mackie K, Chieng R. Letters to the Editor. JOURNAL OF PHARMACY PRACTICE AND RESEARCH 2015. [DOI: 10.1002/j.2055-2335.2008.tb00849.x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
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Dinnel J, Moore BL, Skiver BM, Bose P. Rasburicase in the management of tumor lysis: an evidence-based review of its place in therapy. CORE EVIDENCE 2015; 10:23-38. [PMID: 25610345 PMCID: PMC4298251 DOI: 10.2147/ce.s54995] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Tumor lysis syndrome (TLS) is a potentially life-threatening complication of cancer therapy characterized by two or more of the following laboratory abnormalities: hyperuricemia, hyperkalemia, hypocalcemia, and hyperphosphatemia, with resultant end-organ damage, eg, renal failure, seizures, or cardiac arrhythmias. High-risk patients include those with highly proliferative cancers and/or large tumor burdens, particularly in the setting of highly effective chemotherapy, among other risk factors. Before 2002, antihyperuricemic drug therapy was limited to allopurinol, a xanthine oxidase inhibitor. Rasburicase, a recombinant urate oxidase, was approved by the US Food and Drug Administration for children in 2002 and adults in 2009, ushering in a new era in TLS therapy. We attempted to critically appraise the available evidence supporting the perceived benefits of rasburicase in the management of TLS. A Medline search yielded 98 relevant articles, including 26 retrospective and 22 prospective studies of rasburicase for the treatment of TLS, which were then evaluated to determine the best available evidence for the effectiveness of rasburicase in terms of disease-oriented, patient-oriented, and economic outcomes. Rasburicase is now a standard of care for patients at high risk of TLS despite continuing debate on the correlation between its profound and rapid lowering of plasma uric acid levels with hard patient outcomes, eg, need for renal replacement therapy and mortality. Rasburicase is dramatically effective in lowering plasma uric acid levels. The mortality and cost-effectiveness benefits of this expensive drug remain to be conclusively proven, and well designed, randomized controlled trials are needed to answer these fundamentally important questions.
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Affiliation(s)
- Jennifer Dinnel
- Department of Internal Medicine, Virginia Commonwealth University, VA, USA
| | - Bonny L Moore
- Department of Internal Medicine, Virginia Commonwealth University, VA, USA
| | - Brent M Skiver
- Department of Internal Medicine, Virginia Commonwealth University, VA, USA
| | - Prithviraj Bose
- Department of Internal Medicine, Virginia Commonwealth University, VA, USA ; VCU Massey Cancer Center, Richmond, VA, USA
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25
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Marsh A, Agrawal AK, Feusner JH. Tumor Lysis Syndrome. SUPPORTIVE CARE IN PEDIATRIC ONCOLOGY 2015. [DOI: 10.1007/978-3-662-44317-0_3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
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Clemmons AB, Ensley E, Hoge S, Clark S. Fixed-Dose Rasburicase in Overweight and Obese Patients Versus Normal-Weight Patients. Ann Pharmacother 2014; 48:1152-1158. [DOI: 10.1177/1060028014539144] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Background: Fixed-dose rasburicase (FDR) is common practice in treating hyperuricemia associated with tumor lysis syndrome in adults; however, there is a lack of data regarding the effectiveness of this dosing strategy specifically in the overweight and obese patient populations. Objective: To determine if patient weight per body mass index (BMI) category is associated with failure of initial FDR as defined by the need for additional dose(s) based on a uric acid level (UAL) ≥7.5 mg/dL within 10 days of previous rasburicase administration. Method: Adults who received FDR per institutional guidelines from October 2008 to August 2013 were reviewed. Patients had either a baseline UAL ≥7.5 mg/dL or were considered high risk (leukemia or lymphoma diagnosis with white blood cell count >50 000/mm3 or lactate dehydrogenase level greater than 2 times the upper limit of normal). Patients were stratified by BMI as underweight (<18.5), normal (18.5-24.9), overweight (25-29.9), or obese (30+). Result: Overall, 12 out of 151 patients who received FDR required a repeat dose of rasburicase. The percentage of patients requiring a repeat rasburicase dose was not different between obese/overweight versus normal/underweight patients (8.7% vs 6.4%, P = 0.75). Similarly, there was no difference between obese alone versus normal/underweight patients (12.3% vs 6.4%; P = 0.51). Conclusion: In this retrospective analysis, patient BMI did not correlate with failure of FDR in adults, suggesting that this dosing strategy is efficacious in the adult population.
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Affiliation(s)
- Amber B. Clemmons
- University of Georgia College of Pharmacy, Augusta, GA, USA
- Georgia Regents Medical Center, Augusta, GA, USA
| | - Elizabeth Ensley
- University of Georgia College of Pharmacy, Augusta, GA, USA
- Georgia Regents Medical Center, Augusta, GA, USA
| | - Stephanie Hoge
- University of Georgia College of Pharmacy, Augusta, GA, USA
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Roberts DA, Freed JA. Rasburicase-induced methemoglobinemia in two African-American female patients: an under-recognized and continued problem. Eur J Haematol 2014; 94:83-5. [DOI: 10.1111/ejh.12350] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/15/2014] [Indexed: 11/28/2022]
Affiliation(s)
- Daniel A. Roberts
- Department of Medicine; Beth Israel Deaconess Medical Center and Harvard Medical School; Boston MA USA
| | - Jason A. Freed
- Department of Medicine; Beth Israel Deaconess Medical Center and Harvard Medical School; Boston MA USA
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29
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Herrington JD, Dinh BC. Fixed, low-dose rasburicase for the treatment or prevention of hyperuricemia in adult oncology patients. J Oncol Pharm Pract 2014; 21:111-7. [DOI: 10.1177/1078155214520821] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Purpose Rasburicase is a recombinant urate oxidase enzyme administered to high risk patients or to those with preexisting hyperuricemia from tumor lysis syndrome (TLS). The objective of this retrospective review is to evaluate and characterize the use of fixed, low-dose rasburicase for the treatment of hyperuricemia in adult patients. Patients/Methods A retrospective chart review from 1 October 2005 to 31 December 2011 was conducted in adult oncology patients who received fixed, low-dose rasburicase. Patients who met the inclusion criteria were evaluated for the uric acid level change from baseline and the achievement of uric acid level less than 8 mg/dL. Results Forty-five patients were included in the analysis in which 26 (58%) patients received 3 mg rasburicase. For the 39 patients with baseline uric acid levels 8 mg/dL or higher, 80% achieved a uric acid level lower than 8 mg/dL with a single rasburicase dose. Six patients (13%) required renal replacement therapy despite rasburicase. The median uric acid level reduction 24 h post rasburicase dose 1.5 mg, 3 mg, 4.5 mg, and 6 mg were 5.5, 5.8, 3.8, and 10.05 mg/dL, respectively. There was no clinical difference between obese and non-obese patients in terms of their median uric acid reduction, 5.5 vs. 7 mg/dL, respectively. Conclusion Fixed, low dose rasburicase produced a consistent lowering of uric acid levels and may be utilized in the management of hyperuricemia in TLS. Further study is necessary to determine if a larger fixed dose would be required in those patients with a higher baseline uric acid level.
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Affiliation(s)
| | - Brian C Dinh
- Memorial Hermann Cancer Center, Texas Medical Center, Houston, TX, USA
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Wilson FP, Berns JS. Tumor lysis syndrome: new challenges and recent advances. Adv Chronic Kidney Dis 2014; 21:18-26. [PMID: 24359983 PMCID: PMC4017246 DOI: 10.1053/j.ackd.2013.07.001] [Citation(s) in RCA: 121] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2013] [Revised: 07/10/2013] [Accepted: 07/11/2013] [Indexed: 12/20/2022]
Abstract
Tumor lysis syndrome (TLS) is an oncologic emergency triggered by the rapid release of intracellular material from lysing malignant cells. Most common in rapidly growing hematologic malignancies, TLS has been reported in virtually every cancer type. Central to its pathogenesis is the rapid accumulation of uric acid derived from the breakdown of nucleic acids, which leads to kidney failure by various mechanisms. Kidney failure then limits the clearance of potassium, phosphorus, and uric acid leading to hyperkalemia, hyperphosphatemia, and secondary hypocalcemia, which can be fatal. Prevention of TLS may be more effective than treatment, and identification of at-risk individuals in whom to target preventative efforts remains a key research area. Herein, we discuss the pathophysiology, epidemiology, and treatment of TLS with an emphasis on the kidney manifestations of the disease.
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Affiliation(s)
- F Perry Wilson
- Perelman School of Medicine at the University of Pennsylvania, Hospital of the University of Pennsylvania, Philadelphia, PA
| | - Jeffrey S Berns
- Perelman School of Medicine at the University of Pennsylvania, Hospital of the University of Pennsylvania, Philadelphia, PA.
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Azim HA, Bahr SA, Kamal NS, Koura MA, Tolba R, Gad HA, Morsy A, Attia HM, Iskander I, Hammad A, Hemed MF, Abdallah MF, Sadek KA, Taha AH. One for the road! A study to assess the efficacy of single low-dose regimen of rasburicase in controlling hyperuricaemia in patients with tumour lysis syndrome due to haematological malignancies. Ecancermedicalscience 2013; 7:378. [PMID: 24324529 PMCID: PMC3855003 DOI: 10.3332/ecancer.2013.378] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2013] [Indexed: 11/20/2022] Open
Abstract
We conducted a retrospective audit of six patients with various haematological malignancies (two acute lymphoblastic leukaemia, one acute myeloid leukaemia, and three non-Hodgkin lymphoma); these patients were eligible to receive rasburicase, being at high risk of development of tumour lysis syndrome (TLS). They received a fixed single low-dose regimen of rasburicase (7.5 mg) mainly due to financial restriction, as patients were not supported by the National Health Service and did not have health insurance. We compared uric acid, creatinine levels, and electrolytes (i.e. phosphate, potassium, and calcium) before and after rasburicase administration and also assessed the need for renal replacement therapy after treatment. All six patients had a significant reduction in uric acid levels on the first day, achieving a response rate of 100% (p = 0.008994); creatinine, phosphate, and potassium were reduced significantly as well, with the p values of 0.0439, 0.014326, and 0.002008, respectively; only one patient needed renal replacement therapy in the form of haemodialysis, due to concerns about hyperphosphataemia. Financial difficulties faced either because patients lacked insurance or because of the restricted National Health Service budget in Egypt have resulted in the unavailability of certain modalities of treatment in cancer care and the need to consider more economic yet efficient approaches. Our experience suggests that a single low-dose rasburicase injection (7.5 mg) is an efficient and cost-effective method to control hyperuricaemia in patients with a high risk of developing TLS when compared with the more expensive and extended standard regimen and doses recommended.
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Affiliation(s)
- Hamdy A Azim
- Department of Clinical Oncology, Faculty of Medicine, Cairo University, Cairo, Egypt ; Clinical Oncology and Bone Marrow Transplantation Unit, Manial Specialized University Hospital, Cairo University, Cairo, Egypt
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McBride A, Lathon SC, Boehmer L, Augustin KM, Butler SK, Westervelt P. Comparative evaluation of single fixed dosing and weight-based dosing of rasburicase for tumor lysis syndrome. Pharmacotherapy 2013; 33:295-303. [PMID: 23456733 DOI: 10.1002/phar.1198] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
STUDY OBJECTIVE To evaluate single fixed dosing versus weight-based dosing strategies for rasburicase to determine the minimum dose required to mitigate hyperuricemia in the treatment or prevention of tumor lysis syndrome. DESIGN Retrospective medical record review SETTING Academic medical center PATIENTS A total of 373 patients with a diagnosis of a hematologic malignancy or solid tumor and who received at least one dose of rasburicase over a 6-year period between January 1, 2005, and February 18, 2011; 180 patients received single doses of 3 mg (38 patients), 6 mg (99 patients), or 7.5 mg (43 patients), and 193 patients received weight-based dosing. MEASUREMENTS AND MAIN RESULTS Tumor lysis syndrome laboratory data were recorded at baseline and monitored up to 72 hours after initial rasburicase administration. Median baseline plasma uric acid levels were 6.85 mg/dl, 8.80 mg/dl, 8.00 mg/dl, and 9.20 mg/dl, respectively, in the 3-mg, 6-mg, 7.5-mg, and weight-based dosing groups. Treatment success was defined as a normalized plasma uric acid level (< 7.5 mg/dl) within 24 hours after receiving rasburicase. The mean weight-based dose was 0.16 mg/kg. Six rasburicase treatment failures occurred; two were in the 3-mg group, one was in the 6-mg group, and three were in the weight-based dosing group. At 24 hours after rasburicase administration, no statistically significant differences in treatment success were noted among groups (92.9% vs 97.6% vs 100.0% vs 98.0% in the 3-mg, 6-mg, 7.5-mg, and weight-based dosing groups, respectively, p=0.1238). CONCLUSION The efficacy of all single fixed doses and weight-based dosing strategies evaluated in this study appear to be comparable in normalizing plasma uric acid levels within 24 hours of rasburicase administration. Although use of a 3-mg rasburicase dose may be the most cost-effective treatment strategy in managing hyperuricemia secondary to tumor lysis syndrome, the 6-mg dose resulted in lower sustained uric acid levels after rasburicase administration. Further analysis of patient specific factors contributing to the need for repeat rasburicase administration should be conducted in larger, prospective clinical trials.
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Affiliation(s)
- Ali McBride
- Department of Pharmacy, Arthur G. James Cancer Hospital, The Ohio State University, Columbus, OH 43210, USA.
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Lopez-Olivo MA, Pratt G, Palla SL, Salahudeen A. Rasburicase in tumor lysis syndrome of the adult: a systematic review and meta-analysis. Am J Kidney Dis 2013; 62:481-92. [PMID: 23684124 DOI: 10.1053/j.ajkd.2013.02.378] [Citation(s) in RCA: 47] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2012] [Accepted: 02/14/2013] [Indexed: 01/15/2023]
Abstract
BACKGROUND The use of rasburicase has been evaluated extensively in children, but not in adults. We review the current literature to evaluate its effect on adults. STUDY DESIGN Systematic review and meta-analysis. SETTING & POPULATION Adults receiving rasburicase for tumor lysis syndrome (TLS). SELECTION CRITERIA FOR STUDIES Electronic databases, regulatory documents, and websites were searched up to August 7, 2012. Reference lists of published articles were examined for additional relevant references. Any controlled trial or observational studies (controlled before and after) were included. Studies considering children only or mixing data for children and adults were excluded. INTERVENTION Rasburicase for TLS. OUTCOMES The primary outcome was TLS development. Secondary outcomes included percentage of patients improving, total adverse events, acute kidney failure, deaths, and serum uric acid and creatinine levels. RESULTS 21 studies (24 publications) reported data for 1,261 adult patients, 768 receiving rasburicase for either the treatment or prophylaxis of TLS; these comprised 4 controlled trials and 17 observational studies. No statistically significant differences in clinical TLS development were observed in the controlled trials between the rasburicase and control groups. For the observational studies, 7.4% of patients developed clinical TLS after rasburicase (95% CI, 1.7%-16.7%), 93.4% of patients achieved normalized serum uric acid levels after rasburicase treatment (95% CI, 91.7%-94.6%), 4.4% developed acute kidney injury (95% CI, 3.0%-6.0%), and 2.6% died (95% CI, 0.95%-5.0%). The mean reduction in serum uric acid levels ranged from 5.3-12.8 mg/dL, and for serum creatinine levels, from 0.10-2.1 mg/dL. LIMITATIONS Controlled trials differed in outcomes reported; meta-analysis was not performed. CONCLUSIONS Rasburicase is effective in reducing serum uric acid levels in adults with TLS but at a significant cost, and evidence currently is lacking in adults to report whether rasburicase use improves clinical outcomes compared with other alternatives. Until new evidence is available, use of rasburicase may be limited to adult patients with a high risk of TLS.
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Affiliation(s)
- Maria A Lopez-Olivo
- Department of General Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
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Feng X, Dong K, Pham D, Pence S, Inciardi J, Bhutada NS. Efficacy and cost of single-dose rasburicase in prevention and treatment of adult tumour lysis syndrome: a meta-analysis. J Clin Pharm Ther 2013; 38:301-8. [DOI: 10.1111/jcpt.12061] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2013] [Accepted: 03/04/2013] [Indexed: 12/22/2022]
Affiliation(s)
- X. Feng
- Department of Clinical and Administrative Sciences; California Northstate University College of Pharmacy; Rancho Cordova CA USA
| | - K. Dong
- Department of Clinical and Administrative Sciences; California Northstate University College of Pharmacy; Rancho Cordova CA USA
| | - D. Pham
- Department of Clinical and Administrative Sciences; California Northstate University College of Pharmacy; Rancho Cordova CA USA
| | - S. Pence
- Department of Clinical and Administrative Sciences; California Northstate University College of Pharmacy; Rancho Cordova CA USA
| | - J. Inciardi
- Department of Clinical and Administrative Sciences; California Northstate University College of Pharmacy; Rancho Cordova CA USA
| | - N. S. Bhutada
- Department of Clinical and Administrative Sciences; California Northstate University College of Pharmacy; Rancho Cordova CA USA
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McBride A, Westervelt P. Recognizing and managing the expanded risk of tumor lysis syndrome in hematologic and solid malignancies. J Hematol Oncol 2012; 5:75. [PMID: 23237230 PMCID: PMC3544586 DOI: 10.1186/1756-8722-5-75] [Citation(s) in RCA: 48] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2012] [Accepted: 11/30/2012] [Indexed: 01/13/2023] Open
Abstract
Tumor lysis syndrome (TLS) is widely recognized as a serious adverse event associated with the cytotoxic therapies primarily used in hematologic cancers, such as Burkitt lymphoma and acute lymphoblastic leukemia. In recent years, TLS has been more widely observed, due at least in part to the availability of more effective cancer treatments. Moreover, TLS is seen with greater frequency in solid tumors, and particularly in bulky tumors with extensive metastases and tumors with organ or bone marrow involvement. The consequences of TLS include the serious morbidity and high risk of mortality associated with the condition itself. Additionally, TLS may delay or force an alteration in the patient’s chemotherapy regimen. The changing patterns of TLS, as well as its frequency, in the clinical setting, result in unnecessarily high rates of illness and/or fatality. Prophylactic measures are widely available for patients at risk of TLS, and are considered highly effective. The present article discusses the various manifestations of TLS, its risk factors and management options to prevent TLS from occurring.
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Affiliation(s)
- Ali McBride
- Arthur G, James Cancer Hospital, The Ohio State University, Department of Pharmacy, Room 368 Doan Hall, Columbus, OH 43210, USA.
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Abstract
OBJECTIVES To provide an up-to-date review of current literature on the pathophysiology, diagnosis, and management of five key malignancy-related complications: superior vena cava syndrome, malignant pericardial effusion, malignant spinal cord compression, hypercalcemia, and acute tumor lysis syndrome. DATA SOURCES Database searches and review of relevant medical literature. DATA SYNTHESIS Malignancy-related complications demand increased attention from intensivists due to their frequency and increasing cancer prevalence. Although such complications portend a poor prognosis, proper acute management can improve short-term outcomes by facilitating either definitive care of the underlying malignancy or the institution of appropriate palliative measures. CONCLUSIONS Knowledge of malignancy-induced complications in critically ill patients expedites the ability of the intensivist to properly manage them. Five complications commonly requiring emergency management are addressed in this review. Specifically, superior vena cava syndrome may warrant radiation, chemotherapy, vascular stenting, or surgical resection. Malignant pericardial effusion may require emergency pericardiocentesis if cardiac tamponade develops. Malignant spinal cord compression demands immediate spinal imaging, glucocorticoids, and either surgery or radiation. Hypercalcemia requires aggressive intravenous hydration and a bisphosphonate. Acute tumor lysis syndrome necessitates intravenous hydration, rasburicase, and management of associated electrolyte abnormalities.
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Chan A, Shih V, Chiang J, Chew L, Tay K, Quek R, Tao M, Lim ST. Clinical pharmacy services and research for lymphoma patients at a cancer center. J Oncol Pharm Pract 2012; 19:24-30. [DOI: 10.1177/1078155212449031] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
At the National Cancer Centre Singapore, which is currently the largest ambulatory cancer centre in Singapore, clinical pharmacists have taken upon responsibilities to provide direct pharmaceutical care in the center’s lymphoma team since 2006. Given the complexity and intricacies of lymphoma treatments, clinical pharmacists are often positioned to ensure supportive care is optimized among these patients. Besides management of chemotherapy-related and supportive care issues, clinical pharmacists play a pivotal role in guiding cost-effective and safe prescribing. In collaboration with the medical team, they are also involved in conducting practice research in order to optimize the delivery of pharmaceutical care. In this report, the dedicated services and research activities conducted by clinical pharmacists of a lymphoma team will be discussed.
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Affiliation(s)
- Alexandre Chan
- Department of Pharmacy, National University of Singapore, Singapore; Department of Pharmacy, National Cancer Centre Singapore, Singapore
| | - Vivianne Shih
- Department of Pharmacy, National Cancer Centre Singapore, Singapore
| | - Joen Chiang
- Department of Pharmacy, National Cancer Centre Singapore, Singapore
| | - Lita Chew
- Department of Pharmacy, National University of Singapore, Singapore; Department of Pharmacy, National Cancer Centre Singapore, Singapore
| | - Kevin Tay
- Department of Medical Oncology, National Cancer Centre Singapore, Singapore
| | - Richard Quek
- Department of Medical Oncology, National Cancer Centre Singapore, Singapore
| | - Miriam Tao
- Department of Medical Oncology, National Cancer Centre Singapore, Singapore
| | - Soon Thye Lim
- Department of Medical Oncology, National Cancer Centre Singapore, Singapore
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Chiang J, Chan A, Lian T, Tay K, Quek R, Tao M, Lim ST. Management of tumor lysis syndrome with a single fixed dose of rasburicase in Asian lymphoma patients: a case series and literature review. Asia Pac J Clin Oncol 2012; 7:351-6. [PMID: 22151984 DOI: 10.1111/j.1743-7563.2011.01464.x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
AIM Recently, a number of studies have demonstrated the effectiveness of a single reduced dose of rasburicase for the management of tumor lysis syndrome (TLS) in adults. Whether Asian lymphoma patients similarly respond to a single dose of rasburicase is currently unknown. We aim to assess the efficacy of a single dose rasburicase in preventing TLS in Asian lymphoma patients. METHODS This was a single-center case series of adult lymphoma patients at high risk of TLS who received a single fixed dose of rasburicase. Patients had to have their uric acid, serum creatinine, lactate dehydrogenase and electrolytes monitored for at least 24-48 h post-administration. RESULTS Eleven patients were identified. Majority were Chinese (91%), male (64%) and with a median age of 61 years (range 41-84). All had at least two risk factors for developing TLS. Ten patients received a 6-mg dose and one received 4.5 mg. Prior to rasburicase administration, the mean uric acid level was 835 µmol/L (range 318-1237 µmol/L) and the level 24-h post-administration was 186 µmol/L (range 30-653 µmol/L) (P < 0.001). Eight patients (73%) experienced an improvement of renal function 72-h post-rasburicase. Normalization of serum electrolytes was achieved within 96 h. CONCLUSION Among Asian lymphoma patients who manifested at least two risk factors for developing TLS, a single fixed dose of rasburicase at 6 mg is deemed to be effective for rapidly lowering uric acid levels as well as sustaining reduced levels for up to 72 h.
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Affiliation(s)
- Joen Chiang
- Department of Pharmacy, National Cancer Centre Singapore, Singapore
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Vadhan-Raj S, Fayad LE, Fanale MA, Pro B, Rodriguez A, Hagemeister FB, Bueso-Ramos CE, Zhou X, McLaughlin PW, Fowler N, Shah J, Orlowski RZ, Samaniego F, Wang M, Cortes JE, Younes A, Kwak LW, Sarlis NJ, Romaguera JE. A randomized trial of a single-dose rasburicase versus five-daily doses in patients at risk for tumor lysis syndrome. Ann Oncol 2011; 23:1640-5. [PMID: 22015451 DOI: 10.1093/annonc/mdr490] [Citation(s) in RCA: 61] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND Tumor lysis syndrome (TLS) is a life-threatening disorder characterized by hyperuricemia and metabolic derangements. The efficacy of rasburicase, administered daily for 5 days, has been well established. However, the optimal duration of therapy is unknown in adults. PATIENTS AND METHODS We evaluated the efficacy of rasburicase (0.15 mg/kg) administered as single dose followed by as needed dosing (maximum five doses) versus daily dosing for 5 days in adult patients at risk for TLS. RESULTS Eighty of the 82 patients enrolled received rasburicase; 40 high risk [median uric acid (UA) 8.5 mg/dl; range, 1.5-19.7] and 40 potential risk (UA = 5.6 mg/dl; range, 2.4-7.4). Seventy-nine patients (99%) experienced normalization in their UA within 4 h after the first dose; 84% to an undetectable level (<0.7 mg/dl). Thirty-nine of 40 (98%) patients in the daily-dose arm and 34 of 40 (85%) patients in single-dose arm showed sustained UA response. Six high-risk patients within the single-dose arm required second dose for UA >7.5 mg/dl. Rasburicase was well tolerated; one patient with glucose-6-phosphate dehydrogenase deficiency developed methemoglobinemia and hemolysis. CONCLUSIONS Rasburicase is highly effective for prevention and management of hyperuricemia in adults at risk for TLS. Single-dose rasburicase was effective in most patients; only a subset of high-risk patients required a second dose.
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Affiliation(s)
- S Vadhan-Raj
- Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, MD, USA.
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Affiliation(s)
| | | | - Hans C. Ackerman
- National Institute of Allergy and Infectious Diseases Bethesda, MD
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Bose P, Qubaiah O. A review of tumour lysis syndrome with targeted therapies and the role of rasburicase. J Clin Pharm Ther 2011; 36:299-326. [PMID: 21501203 DOI: 10.1111/j.1365-2710.2011.01260.x] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
WHAT IS KNOWN AND OBJECTIVE Tumour lysis syndrome (TLS) is an oncologic emergency with potentially devastating consequences classically associated with cytotoxic chemotherapy. In recent years, molecularly targeted drugs have assumed an increasingly important role in cancer therapeutics. The possibility of TLS is often overlooked in this setting. Rasburicase, a recombinant urate oxidase, is remarkably effective in treating hyperuricemia, thought to be central to the pathogenesis of renal injury in TLS. Our objective is to review the literature on TLS especially as it pertains to targeted therapies and summarize current knowledge and provide future directions regarding the role of rasburicase in the management of TLS. METHODS A MEDLINE search was conducted using PubMed and the keyphrase 'tumor lysis syndrome' to identify articles describing TLS with a broad range of novel anti-cancer agents. Meeting abstracts were also reviewed. Additionally, the biomedical literature was searched using the keyword 'rasburicase'. RESULTS AND DISCUSSION Tumour lysis syndrome has been described with nearly every class of 'targeted therapy'. This is not surprising as any drug causing death of cancer cells by any mechanism may lead to TLS in the appropriate setting. Although there is a wealth of evidence suggesting that rasburicase is extremely effective in correcting hyperuricemia, prospective trials showing that it improves hard outcomes such as acute renal failure, need for dialysis and mortality are lacking. Furthermore, much lower doses and durations of therapy than approved appear to be effective in controlling hyperuricemia, potentially leading to enormous cost savings. WHAT IS NEW AND CONCLUSION Any effective cancer therapy can lead to TLS. Physicians should consider the risk of TLS on a case-by-case basis and determine appropriate prophylaxis. The role of rasburicase continues to evolve. Randomized controlled trials evaluating clinically relevant outcomes are needed.
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Affiliation(s)
- P Bose
- Division of Hematology/Oncology, Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA.
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Kennedy LD, Koontz S, Rao K. Emerging role of rasburicase in the management of increased plasma uric acid levels in patients with hematologic malignancies. J Blood Med 2011; 2:1-6. [PMID: 22287858 PMCID: PMC3262356 DOI: 10.2147/jbm.s9648] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2011] [Indexed: 11/23/2022] Open
Abstract
Tumor lysis syndrome (TLS) is defined as a group of metabolic derangements that result from the massive and abrupt release of cellular components into the bloodstream after rapid lysis of tumor cells. Breakdown of released materials leads to a number of electrolyte abnormalities, including elevated uric acid concentrations in the blood (hyperuricemia), which carries potentially serious consequences. The diagnosis, prevention, and management of TLS is complicated by variability in definitions, differences in risk factors based on patient- and tumor-specific characteristics, and practitioner preferences in terms of pharmaceutical management strategies. The best prevention and management option for a particular patient depends on the patient’s baseline risk for TLS development, the severity of symptoms in the event of TLS development, practical management considerations, and financial implications of treatment.
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Affiliation(s)
- Leanne D Kennedy
- Wake Forest University Baptist Medical Center, Winston Salem, NC, USA
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Darmon M, Guichard I, Vincent F. Rasburicase and tumor lysis syndrome: lower dosage, consideration of indications, and hyperhydration. J Clin Oncol 2010; 29:e67-8; author reply e69. [PMID: 21149649 DOI: 10.1200/jco.2010.32.6751] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
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Vines AN, Shanholtz CB, Thompson JL. Fixed-dose rasburicase 6 mg for hyperuricemia and tumor lysis syndrome in high-risk cancer patients. Ann Pharmacother 2010; 44:1529-37. [PMID: 20841516 DOI: 10.1345/aph.1p296] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
Abstract
BACKGROUND Rasburicase is indicated for the initial management of plasma uric acid levels in adults receiving anticancer therapy who are at risk for acute tumor lysis syndrome (TLS) and subsequent hyperuricemia. The labeled dose is 0.2 mg/kg/day administered intravenously over 30 minutes for up to 5 days. Our institutional adult guidelines recommend rasburicase 6 mg for uric acid levels >8 mg/dL in most adults with TLS, or 4-8 mg/dL in high-risk patients. Repeat dosing is indicated for uric acid levels >4 mg/dL determined ≥12 hours following the initial dose. OBJECTIVE To determine the efficacy of a single dose of rasburicase 6 mg per institutional adult TLS guidelines to decrease uric acid levels to <4 mg/dL by day 3, as well as to determine the effect on serum creatinine and phosphorus concentrations. The secondary objectives were to evaluate the appropriateness of our institutional guidelines and identify TLS risk factors. METHODS The study was approved by the University of Maryland Medical Center Institutional Review Board. A retrospective review of all adults between July 2008 and February 2009 who received at least one 6-mg dose of rasburicase, with redosing, if indicated, before day 3, was conducted. Subsequent TLS monitoring over 7 days after initial dosing was recorded. Patients were excluded if dosing did not adhere to institutional guidelines. RESULTS We observed a decline in median uric acid levels from 9.2 mg/dL (interquartile range 8.1-10.4) on day 1 to between 1.8 (1.0-3.8) on day 3 and 3.8 mg/dL (2.1-4.4) on day 7 (p < 0.0001) with 2 patients requiring repeat dosing before day 3 (n = 34). The majority of the population was hyperuricemic (>8 mg/dL; 76%) or at high risk for TLS (85%). CONCLUSIONS A 6-mg dose of rasburicase effectively decreased uric acid to <4 mg/dL by day 3, rarely requiring repeat dosing, in a high-risk population.
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Giraldez M, Puto K. A single, fixed dose of rasburicase (6 mg maximum) for treatment of tumor lysis syndrome in adults. Eur J Haematol 2010; 85:177-9. [PMID: 20394650 DOI: 10.1111/j.1600-0609.2010.01457.x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
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Mughal TI, Ejaz AA, Foringer JR, Coiffier B. An integrated clinical approach for the identification, prevention, and treatment of tumor lysis syndrome. Cancer Treat Rev 2009; 36:164-76. [PMID: 20031331 DOI: 10.1016/j.ctrv.2009.11.001] [Citation(s) in RCA: 56] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2009] [Revised: 10/29/2009] [Accepted: 11/03/2009] [Indexed: 11/16/2022]
Abstract
Tumor lysis syndrome (TLS) is a potentially life-threatening metabolic disorder that occurs when tumor cells undergo rapid decomposition spontaneously or in response to cytoreductive therapy. Delayed recognition of the metabolic imbalances caused by the massive release of tumor cell contents may result in clinical complications such as acute kidney injury, seizures, and cardiac arrhythmias. Prevention, the key principle in TLS management, relies on the identification of patients at risk for developing TLS during chemotherapy or because of disease progression. TLS-related risk factors pertain to tumor type (particularly hematologic malignancies), specific tumor characteristics (e.g. bulky tumor, high cellular proliferation rate, sensitivity to cytoreductive therapy), and other host-related factors. A comprehensive grading system proposed by Cairo and Bishop classifies TLS syndromes into laboratory or clinical TLS, thus facilitating TLS prevention and management. The mainstays of TLS management include monitoring of electrolyte abnormalities, vigorous hydration, prophylactic antihyperuricemic therapy with allopurinol, and rasburicase treatment of patients at high TLS risk or with established hyperuricemia. Urine alkalinization and use of diuretics remain controversial clinical practices. In this review, we describe the incidence of, risk factors for, and diagnostic characteristics of TLS and summarize strategies for the prevention and management of TLS-associated metabolic abnormalities, particularly hyperuricemia. We specifically highlight recently published TLS management guidelines, which focus on the prevention of TLS and hyperuricemia based on a patient's level of risk, and the important role of nephrologists in the prevention and treatment of one of the most serious complications of TLS, acute kidney injury.
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Affiliation(s)
- Tariq I Mughal
- Department of Haematology, Guy's & St Thomas's NHS Hospital, London, UK.
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Kennedy LD, Ajiboye VO. Rasburicase for the prevention and treatment of hyperuricemia in tumor lysis syndrome. J Oncol Pharm Pract 2009; 16:205-13. [DOI: 10.1177/1078155209348719] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Purpose. To review current knowledge about tumor lysis syndrome (TLS), a set of metabolic imbalances, including hyperuricemia, that often occur during chemotherapeutic or biotherapeutic treatment of patients with hematologic malignancies. Data sources. English language journal articles indexed in PubMed. Study selection. Recent reviews and original research articles related to TLS, hyperuricemia, and treatment of hyperuricemia were selected for inclusion. Results. The incidence of TLS depends highly on the type of malignancy, its growth characteristics, and the total tumor burden. Patients are at heightened risk if they have hyperuricemia, hypovolemia, or poor renal function before anticancer therapy begins. Recently published guidelines make risk assessment and patient staging more systematic. Prophylactic measures should be used to reduce the risk for TLS in vulnerable patients. Such measures include hydration to facilitate urinary excretion and administration of allopurinol to prevent de novo production of uric acid. If hyperuricemia occurs despite preventative efforts, uric acid concentrations can be reduced with rasburicase, a recombinant, intravenously administered urate oxidase. The cost of rasburicase therapy is substantial but is considerably less than that of hemodialysis and extended hospitalization. Shorter courses or smaller doses of rasburicase than those recommended may be effective in reducing hyperuricemia in some patients, but it is important to recognize that the alternative dosing still awaits validation. Conclusions. Allopurinol and rasburicase are recommended for preventing hyperuricemia in patients at intermediate or high risk for TLS, respectively. If hyperuricemia develops despite preventative measures, rasburicase treatment is an effective method for lowering uric acid concentrations within normal limits.
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Affiliation(s)
- LeAnne D Kennedy
- Department of Pharmacy, Wake Forest University Baptist Medical Center, Winston-Salem, NC, USA,
| | - Violette O Ajiboye
- Department of Pharmacy, Wake Forest University Baptist Medical Center, Winston-Salem, NC, USA
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