scholarly journals Controlling serum uric acid using febuxostat in cancer patients at risk of tumor lysis syndrome

2014 ◽  
Vol 8 (4) ◽  
pp. 1523-1527 ◽  
Author(s):  
MIHOKO TAKAI ◽  
TAKAHIRO YAMAUCHI ◽  
KEI FUJITA ◽  
SHIN LEE ◽  
MIYUKI OOKURA ◽  
...  
Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 919-919 ◽  
Author(s):  
Jorge Cortes ◽  
Karen Seiter ◽  
Richard Thomas Maziarz ◽  
Meir Wetzler ◽  
Michael Craig ◽  
...  

Abstract Tumor lysis syndrome (TLS) is a potentially lethal metabolic complication of chemotherapy or cytolytic antibody therapy usually seen in patients with hematologic malignancies, especially those malignancies with a high proliferative rate, large cellular burden and/or sensitivity to chemotherapy. The prevention and management of TLS includes hydration and reduction of serum uric acid (SUA) levels. Although Allopurinol (ALLO) has had longstanding use for TLS prophylaxis, its efficacy in controlling SUA is limited, especially due of its lack of action on pre-existing hyperuricemia. Rasburicase (RAS), a recombinant urate oxidase, effectively reduces SUA due to conversion of UA into allantoin, a readily excretable and soluble substance. RAS has significant activity in the initial management of TLS-associated acute hyperuricemia in pediatric populations, and is currently indicated in the US for this condition in children and adolescents. A prospective, randomized, controlled phase III study was conducted in adult pts to compare the efficacy in SUA control of RAS (0.20 mg/kg/d, IV) days 1–5, versus RAS+ALLO (RAS 0.20 mg/kg/d, IV days 1–3 plus oral ALLO 300 mg/day days 3–5) versus ALLO alone (300 mg/d) days 1–5. 280 pts (275 evaluable) with hematological malignancies at high or potential risk for TLS were enrolled. 92 pts received RAS, 92 pts received RAS+ALLO, and 91 received ALLO. Treatment arms were well balanced in terms of demographics, baseline characteristics, TLS risk, and percentage of pts with baseline hyperuricemia. The SUA response rate - defined as normalization of SUA (≤ 7.5mg/dl) at days 3–7 was 87.0% in the RAS arm, 78.3% in the RAS+ALLO arm and 65.9% in the ALLO arm. RAS was superior over ALLO (p=0.0009) in the overall study population as well as in pts at high risk TLS (89.0% vs. 62.8%, p=0.0012), and in pts with baseline hyperuricemia (89.5% vs. 52.9%, p=0.0151). The time to control SUA in hyperuricemic pts was 4.1 h in the RAS arm and 27 h in the ALLO arm. The mean SUA area under the curve (AUC) results indicated that there was an 8.4-fold increase in UA exposure in the ALLO arm compared to the RAS arm. There were no significant differences in the incidence or severity of adverse events, serious adverse events or deaths. The majority of RAS and/or ALLO-related adverse events were grade 1 and 2, and most of these events were hypersensitivity-related reactions. No cases of anaphylaxis, methemoglobinemia or hemolysis were observed with RAS treatment. In conclusion, RAS is superior to ALLO in normalization of SUA, with a faster effect, in adult pts at risk for TLS. RAS alone or followed by ALLO are two valid options for this patient population.


2008 ◽  
Vol 26 (16) ◽  
pp. 2767-2778 ◽  
Author(s):  
Bertrand Coiffier ◽  
Arnold Altman ◽  
Ching-Hon Pui ◽  
Anas Younes ◽  
Mitchell S. Cairo

PurposeTumor lysis syndrome (TLS) has recently been subclassified into either laboratory TLS or clinical TLS, and a grading system has been established. Standardized guidelines, however, are needed to aid in the stratification of patients according to risk and to establish prophylaxis and treatment recommendations for patients at risk or with established TLS.MethodsA panel of experts in pediatric and adult hematologic malignancies and TLS was assembled to develop recommendations and guidelines for TLS based on clinical evidence and standards of care. A review of relevant literature was also used.ResultsNew guidelines are presented regarding the prevention and management of patients at risk of developing TLS. The best management of TLS is prevention. Prevention strategies include hydration and prophylactic rasburicase in high-risk patients, hydration plus allopurinol or rasburicase for intermediate-risk patients, and close monitoring for low-risk patients. Primary management of established TLS involves similar recommendations, with the addition of aggressive hydration and diuresis, plus allopurinol or rasburicase for hyperuricemia. Alkalinization is not recommended. Although guidelines for rasburicase use in adults are provided, this agent is currently only approved for use in pediatric patients in the United States.ConclusionThe potential severity of complications resulting from TLS requires measures for prevention in high-risk patients and prompts treatment in the event that symptoms arise. Recognition of risk factors, monitoring of at-risk patients, and appropriate interventions are the key to preventing or managing TLS. These guidelines should assist in the prevention of TLS and improve the management of patients with established TLS.


2021 ◽  
pp. 1-8
Author(s):  
Heather P. May ◽  
Kristin C. Mara ◽  
Erin F. Barreto ◽  
Nelson Leung ◽  
Thomas M. Habermann

2012 ◽  
Vol 23 (6) ◽  
pp. 1640-1645 ◽  
Author(s):  
S. Vadhan-Raj ◽  
L.E. Fayad ◽  
M.A. Fanale ◽  
B. Pro ◽  
A. Rodriguez ◽  
...  

2012 ◽  
Vol 11 (4) ◽  
pp. 284-291
Author(s):  
Armin Sultana ◽  
Afiqul Islam ◽  
Gulshan Akhtar ◽  
Md Abdur Rahman

Objective: To observe the out come of tumor lysis syndrome (TLS) following treatment with hydration and alkalinization in children with acute lymphoblastic leukemia.Methodology: This is an observational study which included 30 diagnosed ALL children who were at high risk of developing TLS in the Department of Pediatric Hematology & Oncology, BSMMU, from January 2010 to July 2010. Result: The mean (±SD) age was found 10.2±2.9 years and maximum (46.7%) numbers were found between 11 to 15 years. Male female ratio was 2.3:1. High risk patients for developing TLS presented with huge organomegaly such as hepatomegaly, splenomegaly, and lymphadenopathy associated with fever, anemia, and bony tenderness. For diagnosis of Acute Lymphoblastic Leukemia (ALL) bone marrow study was done in all patients and immunophenotyping in 40.0% patients. Hydration, Alkalinization, Tab Allopurinol and Oral Aluminum hydroxide were used in all study patients while treatment. WBC and serum uric acid were found higher in all patients during baseline investigation. After hydration and Alkalinization serum potassium, serum phosphate, serum calcium and serum creatinine level were normal within 72 hours and serum uric acid within day five. Mortality was found 6.7% and the cause of mortality was septicemia. DOI: http://dx.doi.org/10.3329/bjms.v11i4.12598 Bangladesh Journal of Medical Science Vol. 11 No. 04 Oct’12  


2010 ◽  
Vol 28 (27) ◽  
pp. 4207-4213 ◽  
Author(s):  
Jorge Cortes ◽  
Joseph O. Moore ◽  
Richard T. Maziarz ◽  
Meir Wetzler ◽  
Michael Craig ◽  
...  

Purpose Rasburicase is effective in controlling plasma uric acid in pediatric patients with hematologic malignancies. This study in adults evaluated safety of and compared efficacy of rasburicase alone with rasburicase followed by oral allopurinol and with allopurinol alone in controlling plasma uric acid. Patients and Methods Adults with hematologic malignancies at risk for hyperuricemia and tumor lysis syndrome (TLS) were randomly assigned to rasburicase (0.20 mg/kg/d intravenously days 1-5), rasburicase plus allopurinol (rasburicase 0.20 mg/kg/d days 1 to 3 followed by oral allopurinol 300 mg/d days 3 to 5), or allopurinol (300 mg/d orally days 1 to 5). Primary efficacy variable was plasma uric acid response rate defined as percentage of patients achieving or maintaining plasma uric acid ≤ 7.5 mg/dL during days 3 to 7. Results Ninety-two patients received rasburicase, 92 rasburicase plus allopurinol, and 91 allopurinol. Plasma uric acid response rate was 87% with rasburicase, 78% with rasburicase plus allopurinol, and 66% with allopurinol. It was significantly greater for rasburicase than for allopurinol (P = .001) in the overall study population, in patients at high risk for TLS (89% v 68%; P = .012), and in those with baseline hyperuricemia (90% v 53%; P = .015). Time to plasma uric acid control in hyperuricemic patients was 4 hours for rasburicase, 4 hours for rasburicase plus allopurinol, and 27 hours for allopurinol. Conclusion In adults with hyperuricemia or at high risk for TLS, rasburicase provided control of plasma uric acid more rapidly than allopurinol. Rasburicase was well tolerated as a single agent and in sequential combination with allopurinol.


2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Yohannes Belay ◽  
Ketsela Yirdaw ◽  
Bamlaku Enawgaw

Tumor lysis syndrome is a metabolic complication that may follow the initiation of cancer therapy. It commonly occurs in hematological malignant patients particularly non-Hodgkin’s lymphoma and acute leukemia due to chemotherapy or spontaneously. It is characterized by a biochemical abnormality such as hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcemia and its clinical outcome is directly related to these biochemical abnormalities. Prevention and treatment of tumor lysis syndrome depend on immediate recognition of patients at risk. Therefore, identifying patients at risk and prophylactic measures are important to minimize the clinical consequences of tumor lysis syndrome. Patients with low risk should receive hydration and allopurinol. On the other hand patients with high risk should receive hydration and rasburicase in an inpatient setting. It is important to start therapy immediately, to correct all parameters before cancer treatment, to assess risk level of patients for TLS, and to select treatment options based on the risk level. In this review a comprehensive search of literatures was performed using MEDLINE/PubMed, Hinari, the Cochrane library, and Google Scholar to summarize diagnostic criteria, incidence, predicting factors, prevention, and treatment options for tumor lysis syndrome in patients with hematological malignancies.


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