Rasburicase
CancerIndex Home - Guide to Internet Resources for Cancer Home > Treatments > Chemotherapy > Drugs > Rasburicase
Found this page useful?

Menu: Rasburicase

Web Resources: Rasburicase
Recent Research Publications

Web Resources: Rasburicase (4 links)


Recent Research Publications

Galardy PJ, Hochberg J, Perkins SL, et al.
Rasburicase in the prevention of laboratory/clinical tumour lysis syndrome in children with advanced mature B-NHL: a Children's Oncology Group Report.
Br J Haematol. 2013; 163(3):365-72 [PubMed] Article available free on PMC after 01/11/2014 Related Publications
Laboratory (LTLS) and clinical (CTLS) tumour lysis syndrome (TLS) are frequent complications in newly diagnosed children with advanced mature B cell non-Hodgkin lymphoma (B-NHL). Rasburicase, compared to allopurinol, results in more rapid reduction of uric acid in paediatric patients at risk for TLS. However, the safety and efficacy of rasburicase for the treatment or or prevention of TLS has not been prospectively evaluated. Children with newly diagnosed stage III-IV, bone marrow(+) and/or central nervous system(+) mature B-NHL received hydration and rasburicase prior to cytoreductive therapy. Rasburicase was safe and well-tolerated and there were no grade III-IV toxicities probably or directly related to rasburicase. Patients with an initial lactate dehydrogenase ≥2× upper limit of normal had a significantly elevated uric acid level (P = 0·005), increased incidence of TLS (P-0·005) and lower glomerular filtration rate (GFR; P < 0·001). Following rasburicase, there was only a 9% and 5% incidence of LTLS and CTLS, respectively. Furthermore, there was a significant improvement in estimated GFR from Day 0 to Day 7 following rasburicase (P = 0·0007) and only 1·3% of patients required new onset renal assisted support after rasburicase administration. A TLS strategy incorporating rasburicase prior to cytoreductive chemotherapy proved safe and effective in preventing new onset renal failure and was associated with a significant improvement in GFR.

Related: Cyclophosphamide Cytarabine Non Hodgkin's Lymphoma Childhood Non-Hodgkin's Lymphoma NHL - Molecular Biology Methotrexate Vincristine Rituximab (Mabthera) Rasburicase


Darmon M, Vincent F, Camous L, et al.
Tumour lysis syndrome and acute kidney injury in high-risk haematology patients in the rasburicase era. A prospective multicentre study from the Groupe de Recherche en Réanimation Respiratoire et Onco-Hématologique.
Br J Haematol. 2013; 162(4):489-97 [PubMed] Related Publications
In tumour lysis syndrome (TLS), metabolic alterations caused by the destruction of malignant cells manifest as laboratory abnormalities with (clinical TLS) or without (laboratory TLS) organ dysfunction. This prospective multicentre cohort study included 153 consecutive patients with malignancies at high risk for TLS (median age 54 years (interquartile range, 38-66). Underlying malignancies were acute leukaemia (58%), aggressive non-Hodgkin lymphoma (29.5%), and Burkitt leukaemia/lymphoma (12.5%). Laboratory TLS developed in 17 (11.1%) patients and clinical TLS with acute kidney injury (AKI) in 30 (19.6%) patients. After adjustment for confounders, admission phosphates level (odds ratio [OR] per mmol/l, 5.3; 95% confidence interval [95% CI], 1.5-18.3), lactic dehydrogenase (OR per x normal, 1.1; 95%CI, 1.005-1.25), and disseminated intravascular coagulation (OR, 4.1; 95%CI, 1.4-12.3) were associated with clinical TLS; and TLS was associated with day-90 mortality (OR, 2.45; 95%CI, 1.09-5.50; P = 0.03). In this study, TLS occurred in 30.7% of high-risk patients. One third of all patients experienced AKI, for which TLS was an independent risk factor. TLS was associated with increased mortality, indicating a need for interventional studies aimed at decreasing early TLS-related deaths in this setting.

Related: Haematological Malignancies & Realted Disorders Rasburicase


Chao CT, Chiang CK
Rasburicase for huge hepatocellular carcinoma with tumor lysis syndrome: case report.
Med Princ Pract. 2012; 21(5):498-500 [PubMed] Related Publications
OBJECTIVE: To report a case of huge hepatocellular carcinoma associated with tumor lysis syndrome and its management.
CLINICAL PRESENTATION AND INTERVENTION: A 51-year-old hepatitis B carrier visited our clinic with progressive weight loss over recent months. Abdominal ultrasonography and magnetic resonance imaging revealed a huge hepatic mass in a cirrhotic liver, identified as hepatocellular carcinoma. A hepatologist and surgeon recommended transarterial chemoembolization followed by hepatectomy. The patient underwent the procedure, with the complication of tumor lysis syndrome. He was treated with a single high dose (9 mg) of rasburicase and his clinical condition improved dramatically, with acute kidney injury subsiding without emergent hemodialysis.
CONCLUSIONS: This was a case of hepatocellular carcinoma with tumor lysis syndrome and acute kidney injury, treated successfully with rasburicase.

Related: Liver Cancer Rasburicase


McCurdy MT, Shanholtz CB
Oncologic emergencies.
Crit Care Med. 2012; 40(7):2212-22 [PubMed] Related Publications
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.

Related: Cancer Prevention and Risk Reduction


Malaguarnera G, Giordano M, Malaguarnera M
Rasburicase for the treatment of tumor lysis in hematological malignancies.
Expert Rev Hematol. 2012; 5(1):27-38 [PubMed] Related Publications
Tumor lysis syndrome (TLS) is a common oncologic emergency in patients with hematological malignancies sensitive to cytotoxic treatment that present a high proliferative rate. High proliferative cancer rate, high sensitivity of cytotoxic treatment and renal failure represent risk factors for development of TLS. TLS is also responsible for several electrolytic alterations, such as hyperuricemia, hyperkalemia, hyperphosphatemia and hypocalcemia. There are different established therapeutic options for the treatment of TLS such as hydration, allopurinol and rasburicase. Rasburicase reduces uric acid levels within 4 h, both in pediatric and adult patients, catalyzing the oxidation of uric acid into allantoin, rapidly excreted by the kidneys. Rasburicase is well tolerated and was approved in the EU and in the USA for the management of acute hyperuricemia.

Related: Haematological Malignancies & Realted Disorders Rasburicase


Chiang J, Chan A, Lian T, et al.
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. 2011; 7(4):351-6 [PubMed] Related Publications
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.

Related: Rasburicase


Ahn YH, Kang HJ, Shin HY, et al.
Tumour lysis syndrome in children: experience of last decade.
Hematol Oncol. 2011; 29(4):196-201 [PubMed] Related Publications
The strategy against tumour lysis syndrome (TLS) had been hyperhydration, urine alkalinization, and allopurinol. Recently, rasburicase was added to the armament against this life-threatening condition. In Korea, rasburicase is used as a rescue therapy for cases with allopurinol-resistant hyperuricemia, because of the restriction by the National Health Insurance. We reviewed our experiences to re-assess the risk factors of TLS and the efficacy of rasburicase. Medical records were retrospectively reviewed for 396 children who were diagnosed as positive with acute leukemia and non-Hodgkin lymphoma between the years 2000 and 2009. The risk factors for TLS were analyzed statistically, and those before and after the availability of rasburicase were compared. Sixty eight patients (17.2%) had TLS. Multivariate analysis showed that pre-chemotherapy hypophosphatemia was a risk factor for TLS, in addition to the known risk factors of hyperuricemia and high lactate dehydrogenase concentration. The availability of rasburicase as a rescue therapy did not negate the importance of uric acid as a risk factor of TLS. Rasburicase as a second line treatment for intractable hyperuricemia was not effective in reducing the incidence of TLS. Pre-chemotherapy hypophosphatemia was a significant independent risk factor for TLS.

Related: Leukemia Childhood Leukaemia Leukemia - Molecular Biology Non Hodgkin's Lymphoma Childhood Non-Hodgkin's Lymphoma NHL - Molecular Biology Rasburicase


Will A, Tholouli E
The clinical management of tumour lysis syndrome in haematological malignancies.
Br J Haematol. 2011; 154(1):3-13 [PubMed] Related Publications
Tumour lysis syndrome (TLS) is caused by the disintegration of malignant cells, usually following the instigation of chemotherapy, although it may already be established at the time of initial presentation in a minority of cases. As a direct consequence of malignant cell breakdown, intracellular ions, proteins, nucleic acids and their metabolites are released into the plasma causing the characteristic metabolic abnormalities of TLS; hyperuricaemia, hyperkalaemia, hyperphosphataemia and hypocalcaemia. In many cases the release of large amounts intracellular contents is so abrupt that the normal homeostatic mechanisms are rapidly overwhelmed and without prompt, effective management, the clinical effects of TLS soon become apparent.

Related: Haematological Malignancies & Realted Disorders Rasburicase


Murray MJ, Metayer LE, Mallucci CL, et al.
Intra-abdominal metastasis of an intracranial germinoma via ventriculo-peritoneal shunt in a 13-year-old female.
Br J Neurosurg. 2011; 25(6):747-9 [PubMed] Related Publications
A 13-year-old patient presented with massive intra-abdominal metastasis and spontaneous acute tumour lysis syndrome, 17-months after VP shunt placement for metastatic pineal germinoma treated with cranio-spinal-irradiation. Hyperhydration/rasburicase improved renal function, allowing chemotherapy with subsequent surgery. The patient remains event-free 34-months later. Risk of intra-abdominal metastasis from VP shunts is discussed.


Bauters T, Mondelaers V, Robays H, et al.
Methemoglobinemia and hemolytic anemia after rasburicase administration in a child with leukemia.
Int J Clin Pharm. 2011; 33(1):58-60 [PubMed] Related Publications
CASE: We report a case of simultaneous methemoglobinemia and hemolytic anemia, probably related to the use of rasburicase, in a child starting treatment for acute lymphoblastic leukemia (ALL). In addition, the patient developed symptoms of pancreatitis. All complications resolved after 3 days of supportive therapy.
CONCLUSION: Although usually well tolerated in pediatrics, physicians prescribing rasburicase should be aware of these possible life-threatening adverse reactions.

Related: Acute Lymphocytic Leukemia (ALL) Childhood Acute lymphoblastic leukaemia (ALL) ALL - Molecular Biology Rasburicase


Schuman S, Pearson JM, Lucci JA, Twiggs LB
Metastatic gestational trophoblastic neoplasia complicated by tumor lysis syndrome, heart failure, and thyrotoxicosis: a case report.
J Reprod Med. 2010 Sep-Oct; 55(9-10):441-4 [PubMed] Related Publications
BACKGROUND: Tumor lysis syndrome (TLS) is an extremely rare complication of solid tumors and is more frequently observed in patients with hematologic malignancies. This report describes a novel approach to the management of a rare case of TLS in metastatic gestational trophoblastic neoplasia (GTN).
CASE: A 17-year-old female presented 8 weeks postpartum with severe anemia, thyrotoxicosis, and elevated serum beta-human chorionic gonadotropin (beta-hCG). Imaging studies confirmed metastatic GTN to the lungs. The patient developed grade 4 TLS after the first cycle of etoposide, methotrexate, dactinomycin, cyclophosphamide, and vincristine (EMA-CO). She did not respond to standard treatment of aggressive hydration and allupurinol and continued to be in renal failure with elevated uric acid. A single dose of recombinant urate oxidase, rasburicase, rendered the uric acid level undetectable in 3 days and completely reversed the renal failure, avoiding hemodialysis. Three more cycles of EMA-CO were then administered. Subsequently, the patient developed congestive heart failure and was switched to single-agent actinomycin-D. Beta-hCG became negative after 5 cycles, and her ejection fraction returned to baseline.
CONCLUSION: This is a rare case of TLS in the setting of metastatic GTN. To our knowledge this is the first reported case of utilizing rasburicase for the management of TLS in GTN.

Related: Cyclophosphamide Dactinomycin Etoposide Methotrexate Vincristine Rasburicase


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(10):1529-37 [PubMed] Related Publications
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.

Related: Haematological Malignancies & Realted Disorders Cancer Prevention and Risk Reduction Rasburicase


Trifilio SM, Pi J, Zook J, et al.
Effectiveness of a single 3-mg rasburicase dose for the management of hyperuricemia in patients with hematological malignancies.
Bone Marrow Transplant. 2011; 46(6):800-5 [PubMed] Related Publications
Rasburicase was administered at a fixed dose of 3 mg to treat 287 episodes of elevated serum uric acid levels (>7 mg/dL) in 247 adult patients with hematological malignancies. The median total dose of 36 μg/kg (range: 18-65) was a fraction of the recommended total pediatric dose of 0.75-1.0 mg/kg. The median change in uric acid levels at 24 h was -4.1 mg/dL (range: -12 to +1) and -45% (range: -95 to +9). Uric acid levels normalized at 24 h in 72% of patients. There was no relationship between the weight-based dose and uric acid decline. The only predictor of success was the baseline uric acid; the failure rate was 84% with baseline level >12 mg/dL and 18% if it was ≤ 12. Uric acid levels continued to decline beyond 24 h in most patients without additional treatment. Serum creatinine remained stable over 24 h, and declined over 48 h and 7 days. There was no relationship between the extent of reduction in uric acid levels and serum creatinine. We conclude that a single 3-mg dose of rasburicase, used with close monitoring, is sufficient to treat most adults with uric acid levels up to 12 mg/dL.

Related: Haematological Malignancies & Realted Disorders Rasburicase


Cortes J, Moore JO, Maziarz RT, et al.
Control of plasma uric acid in adults at risk for tumor Lysis syndrome: efficacy and safety of rasburicase alone and rasburicase followed by allopurinol compared with allopurinol alone--results of a multicenter phase III study.
J Clin Oncol. 2010; 28(27):4207-13 [PubMed] Related Publications
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.

Related: Haematological Malignancies & Realted Disorders USA Rasburicase


Meinhardt A, Burkhardt B, Zimmermann M, et al.
Phase II window study on rituximab in newly diagnosed pediatric mature B-cell non-Hodgkin's lymphoma and Burkitt leukemia.
J Clin Oncol. 2010; 28(19):3115-21 [PubMed] Related Publications
PURPOSE: The activity of rituximab in pediatric B-cell non-Hodgkin's lymphoma (B-NHL) has not yet been determined. We conducted a phase II window study to examine activity and tolerability of rituximab in newly diagnosed pediatric B-NHL.
PATIENTS AND METHODS: Patients younger than age 19 years with CD20(+) B-NHL with at least one measurable site were eligible. Treatment consisted of rituximab at 375 mg/m(2) administered intravenously on day 1; concomitant therapy consisted of rasburicase, intrathecally (IT) triple drug (methotrexate, cytarabine, and prednisolone) on days 1 and 3 for CNS-positive patients and steroids only for anaphylaxis. Response criterion was the product of the two largest perpendicular diameters of one to three lesions and/or the percentage of blasts in bone marrow (BM) or peripheral blood (PB) within 24 hours before rituximab and on day 5. Responders had > or = 25% decrease of at least one lesion or BM or PB blasts and no disease progress at other sites. Response rate (RR) was set at 45% for unfavorable activity or at 65% for favorable activity.
RESULTS: From April 2004 to August 2008, 136 patients were enrolled. National Cancer Institute Common Toxicity Criteria 3/4 toxicities attributable to rituximab were general condition, 15%; fatigue, 13%; anaphylaxis, 7%; infection, 3%; glutamic-oxaloacetic transaminase/glutamic-pyruvic transaminase, 8%; no capillary leakage; and no toxic death. Forty-nine patients were not evaluable for response because of withdrawal from the study (n = 16), IT therapy in CNS-negative patients (n = 8), corticosteroid treatment (n = 3), technical inadequacy of response evaluation (n = 21), or no evaluable lesion (n = 1). Of 87 evaluable patients, 36 were responders (RR, 41.4%; 95% CI, 31% to 52%); among them, 27 of 67 with Burkitt lymphoma and seven of 15 with diffuse large B-cell lymphoma. A response was more frequently observed in BM (12 of 18) compared with solid tumor lesions (36 of 108; P = .007).
CONCLUSION: Rituximab is active as a single-agent in pediatric B-NHL even though the RR was lower than requested in the phase II plan.

Related: Monoclonal Antibodies Non Hodgkin's Lymphoma Childhood Non-Hodgkin's Lymphoma NHL - Molecular Biology Rituximab (Mabthera)


Bercovitz RS, Greffe BS, Hunger SP
Acute tumor lysis syndrome in a 7-month-old with hepatoblastoma.
Curr Opin Pediatr. 2010; 22(1):113-6 [PubMed] Related Publications
Acute tumor lysis syndrome (TLS) is characterized by the triad of hyperuricemia, hyperkalemia, and hyperphosphatemia and is caused by the death of tumor cells and release of intracellular contents into the circulation. This syndrome is most frequently associated with hematopoietic malignancies with a high growth fraction, including acute leukemias and lymphomas, but can be encountered in patients with nonhematopoietic solid tumors. Acute tumor lysis is typically precipitated by chemotherapy leading to rapid cell death, but may also occur spontaneously prior to treatment. In severe cases, the metabolic abnormalities of TLS can cause renal failure, cardiac arrhythmias, and death. Standard therapies include intravenous hydration, alkalinization of the urine to increase the solubility of uric acid, and administration of allopurinol to block production of uric acid. Recombinant urate oxidase (rasburicase) is a newer agent that directly cleaves uric acid. It is important for the clinician to maintain a high level of clinical suspicion for TLS when initiating therapy in children newly diagnosed with cancer, including those with solid tumors, and to know how to prevent and treat this potentially deadly metabolic complication.

Related: Cisplatin Fluorouracil Liver Cancer Vincristine


Kikuchi A, Kigasawa H, Tsurusawa M, et al.
A study of rasburicase for the management of hyperuricemia in pediatric patients with newly diagnosed hematologic malignancies at high risk for tumor lysis syndrome.
Int J Hematol. 2009; 90(4):492-500 [PubMed] Related Publications
Tumor lysis syndrome (TLS), including hyperuricemia, is a frequent serious complication in patients with hematologic malignancies. This study in Japanese patients evaluated the efficacy, safety, and pharmacokinetic profile of rasburicase in pediatric patients with hematologic malignancies. Patients aged <18 years at high risk for TLS, with newly diagnosed hematologic malignancies, were randomized to intravenous rasburicase 0.15 mg/kg/day (n = 15) or 0.20 mg/kg/day (n = 15) for 5 days. Chemotherapy was started 4-24 h after the first rasburicase dose. Response was defined as a reduction in plasma uric acid to < or = 6.5 mg/dL (patients <13 years) or < or = 7.5 mg/dL (patients > or = 13 years) by 48 h after the first administration, lasting until 24 h after the final administration. Response rates were 93.3 and 100% with rasburicase 0.15 and 0.20 mg/kg/day, respectively. Uric acid levels declined rapidly within 4 h of starting rasburicase administration in both groups. Most adverse events were related to the underlying chemotherapy regimens. Two hypersensitivity reactions, including grade 1/2 pruritus, were considered to be related to rasburicase. Rasburicase is effective and well tolerated for the management of hyperuricemia in Japanese pediatric patients at high risk of developing TLS.

Related: Haematological Malignancies & Realted Disorders Rasburicase


Ishizawa K, Ogura M, Hamaguchi M, et al.
Safety and efficacy of rasburicase (SR29142) in a Japanese phase II study.
Cancer Sci. 2009; 100(2):357-62 [PubMed] Related Publications
The purpose of this study was to investigate the safety profile of SR29142 when administered as a single agent both prior to chemotherapy and during treatment, and to compare the efficacy of SR29142 administered at two dose levels in adult Japanese patients with leukemia or lymphoma. During this open-label, multicenter, phase II study, patients received SR29142 for 5 days, administered at either 0.15 or 0.20 mg/kg per day. Chemotherapy was started 4–24 h after the first infusion of SR29142. The primary end-point was overall response rate, defined as the normalization of plasma uric acid to 7.5 mg/dL or less, from 48 h after the first infusion to 24 h after the last infusion of SR29142. SR29142-related adverse events including hypersensitivity (allergic) reactions were assessed. Overall, 50 patients received SR29142 at either 0.15 mg/kg per day (n = 25) or 0.20 mg/kg per day (n = 25) followed by chemotherapy. The overall response rate was 100.0% (95% confidence interval, 86.3–100.0%) with 0.15 mg/kg and 96.0% (95% confidence interval, 79.6–99.9%) with 0.20 mg/kg. Both dose levels of SR29142 were equally effective at reducing plasma uric acid levels. In six patients, seven drug-related adverse events of grade 1/2 occurred before chemotherapy. SR29142-related, hypersensitivity-associated reactions occurred in three patients, and rash, anorexia, application site pain and pyrexia occurred in one patient each; only five patients (10%) showed anti-SR29142 antibodies by day 29. In conclusion, SR29142 is effective at reducing plasma uric acid levels with a tolerable safety profile as a single agent both prior to chemotherapy and during treatment.

Related: Leukemia Rasburicase


Calvo-Villas JM, Urcuyo BM, Umpierrez AM, Sicilia F
Acute tumor lysis syndrome during oral fludarabine treatment for chronic lymphocytic leukemia. Role of treatment with rasburicase.
Onkologie. 2008; 31(4):197-9 [PubMed] Related Publications
INTRODUCTION: Oral fludarabine is the first oral formulation of a purine analogue available for clinical use which has produced encouraging results in patients with B-cell chronic lymphocytic leukemia (CLL). It has a similar tolerability profile to that of the intravenous formulation. Acute tumor lysis syndrome (TLS) induced by fludarabine appears to be a fairly unusual complication during the treatment of CLL.
CASE REPORT: The present report describes the case of a 78-year-old man who developed acute renal failure associated with TLS following the first course of oral fludarabine. Laboratory investigations fulfilled the TLS typical criteria, including hyperkalemia, marked hyperuricemia, hyperphosphatemia, hypocalcemia, and acute renal failure. Despite the many documented side effects of oral fludarabine, there is only one similar case of oral fludarabine-induced TLS reported to date. Conventional therapy with short-term supportive hemodialysis and a short treatment of rasburicase for 2 days achieved a complete recovery of renal function and a decrease of the urate level to within the normal range.
CONCLUSIONS: Clinicians should be alert to this potentially life-threatening metabolic emergency among CLL patients treated with oral fludarabine.

Related: Chronic Lymphocytic Leukemia (CLL) CLL - Molecular Biology Rasburicase Fludarabine


Bertrand Y, Mechinaud F, Brethon B, et al.
SFCE (Société Française de Lutte contre les Cancers et Leucémies de l'Enfant et de l'Adolescent) recommendations for the management of tumor lysis syndrome (TLS) with rasburicase: an observational survey.
J Pediatr Hematol Oncol. 2008; 30(4):267-71 [PubMed] Related Publications
Rasburicase (Fasturtec), a recombinant urate oxidase, is highly effective in preventing and treating hyperuricemia in children with hematologic malignancies. We conducted a prospective, multicenter observational study in 174 patients at 8 pediatric hemato-oncology centers to establish whether the SFCE (Société Française de Lutte contre les Cancers et Leucémies de l'Enfant et de l'Adolescent) recommendations for the use of rasburicase in the management of pediatric patients at risk of tumor lysis syndrome (TLS) are valid in routine clinical practice. Patients were classified as being at high or low risk of TLS according to the Children's Oncology Group criteria and were treated in accordance with the SFCE recommendations. The primary end point was the number of patients requiring a higher dose of rasburicase or a longer duration of treatment than advised in the SFCE recommendations. Of the 135 patients at high risk of TLS, 27 patients received a higher dose and 35 patients received a longer duration of treatment. Some patients received treatment with rasburicase for less than the recommended duration (median 4 d for high-risk patients). One patient required hemodialysis. Only minor adjustments to the SFCE recommendations were required to ensure the optimal use of rasburicase in pediatric patients at risk of TLS.

Related: Haematological Malignancies & Realted Disorders Rasburicase


Rényi I, Bárdi E, Udvardi E, et al.
Prevention and treatment of hyperuricemia with rasburicase in children with leukemia and non-Hodgkin's lymphoma.
Pathol Oncol Res. 2007; 13(1):57-62 [PubMed] Related Publications
To prevent acute renal failure in children at risk for developing tumor lysis syndrome due to acute lymphoblastic leukemia or non-Hodgkin's lymphoma treated according to international BFM protocols, we investigated recombinant urate oxidase (rasburicase) in the first Central European openlabeled, prospective, multicenter phase IV trial. Rasburicase was administered intravenously, at 0.2 mg/kg for 5 consecutive days to 36 patients. Blood levels of uric acid, creatinine, phosphorus, calcium, lactate dehydrogenase and complete blood count were measured daily during rasburicase treatment and on days 6, 7 and 12. Initial uric acid level decreased significantly by 4 hours (from 343 micromol/L to 58 micromol/L, p<0.001), except for one steroid-resistant patient who required hemodialysis on day 14 after having introduced combined cytostatic treatment. Comparing the data of a subgroup of 12 patients receiving rasburicase with that of a historic cohort of 14 patients treated with allopurinol indicated the superiority of rasburicase over allopurinol in prophylaxis and treatment of hyperuricemia in children with leukemia and lymphoma.

Related: Leukemia Childhood Leukaemia Leukemia - Molecular Biology Non Hodgkin's Lymphoma Childhood Non-Hodgkin's Lymphoma NHL - Molecular Biology Rasburicase


LaRosa C, McMullen L, Bakdash S, et al.
Acute renal failure from xanthine nephropathy during management of acute leukemia.
Pediatr Nephrol. 2007; 22(1):132-5 [PubMed] Related Publications
Tumor lysis syndrome is a potentially life-threatening complication of induction chemotherapy for treatment of lymphoproliferative malignancies. Serious complications of tumor lysis syndrome are rare with the preemptive use of allopurinol, rasburicase, and urine alkalinization. We report a case of oliguric acute renal failure due to bilateral xanthine nephropathy in an 11-year-old girl as a complication of tumor lysis syndrome during the treatment of T-cell acute lymphoblastic leukemia. Xanthine nephrolithiasis results from the inhibition of uric acid synthesis via allopurinol which increases plasma and urinary xanthine and hypoxanthine levels. Reports of xanthine nephrolithiasis as a cause of tumor lysis syndrome are rare in the absence of defects in the hypoxanthine-guanine phosphoribosyl transferase (HGPRT) enzyme. Xanthine nephropathy should be considered in patients who develop acute renal failure following aggressive chemotherapy with appropriate tumor lysis syndrome prophylaxis. Urine measurements for xanthine could aid in the diagnosis of patients with nephrolithiasis complicating tumor lysis syndrome. Allopurinal dosage should be reduced or discontinued if xanthine nephropathy is suspected.

Related: Acute Lymphocytic Leukemia (ALL) Childhood Acute lymphoblastic leukaemia (ALL) ALL - Molecular Biology


Oldfield V, Perry CM
Spotlight on rasburicase in anticancer therapy-induced hyperuricemia.
BioDrugs. 2006; 20(3):197-9 [PubMed] Related Publications
Intravenous rasburicase (Elitek), Fasturtec) is the first recombinant uricolytic agent. It is indicated for the management of anticancer therapy-induced hyperuricemia in pediatric patients in the EU and US, and in adult patients in the EU. Rasburicase is effective and generally well tolerated in adult and pediatric patients with, or at risk of developing, anticancer therapy-induced hyperuricemia. It is associated with potentially serious hematologic adverse events and hypersensitivity reactions, which must be considered prior to and during administration; rasburicase is contraindicated in patients predisposed to hemolysis or methemoglobinemia and in patients with glucose-6-phosphate dehydrogenase deficiency. Unlike allopurinol, rasburicase acts on existing uric acid concentrations. Rasburicase treatment resulted in significantly less systemic exposure to uric acid and a quicker therapeutic response than allopurinol in pediatric patients; further studies are needed to determine the comparative efficacy and tolerability of rasburicase versus allopurinol in adult patients. Although further pharmacoeconomic data would be useful, rasburicase was most cost effective for the prevention of hyperuricemia in children and for treatment of this condition in adults. Thus, rasburicase is a useful option for the prophylaxis or treatment of anticancer therapy-induced hyperuricemia in both adult and pediatric patients.

Related: Cancer Prevention and Risk Reduction Rasburicase


Trifilio S, Gordon L, Singhal S, et al.
Reduced-dose rasburicase (recombinant xanthine oxidase) in adult cancer patients with hyperuricemia.
Bone Marrow Transplant. 2006; 37(11):997-1001 [PubMed] Related Publications
Recombinant urate oxidase (rasburicase) lowers uric acid levels rapidly to very low levels at the labeled dose of 0.15-0.2 mg/kg daily for 5 days. Our past experience showed that a lower dose (3 mg) lowered uric acid levels sufficiently in most patients. A retrospective review was conducted to determine the effect of a fixed 3 mg dose of rasburicase in 43 adult patients with cancer undergoing hematopoietic stem cell transplantation or receiving chemotherapy who had elevated or rising uric acid levels (6.4-16.8 mg/dl; median 9.6). Six patients received a second dose of rasburicase (3 mg in four patients and 1.5 mg in two patients) 24 h later. Patients received allopurinol, adequate hydration, as well as other supportive therapy as required. Uric acid levels declined by 6-95% (median 43%) within the first 24 h after rasburicase administration, and levels at 48 h were 9-91% (median 65%) lower than the baseline levels. Serum creatinine changed by < or =10% in 21 patients, increased by >10% in four patients and decreased by >10% in 18 patients. No significant renal dysfunction developed in any of the patients. We conclude that rasburicase is effective in lowering uric acid levels at a fixed dose of 3 mg, which is much lower than the recommended dose.

Related: Cancer Prevention and Risk Reduction Rasburicase


Hutcherson DA, Gammon DC, Bhatt MS, Faneuf M
Reduced-dose rasburicase in the treatment of adults with hyperuricemia associated with malignancy.
Pharmacotherapy. 2006; 26(2):242-7 [PubMed] Related Publications
Tumor lysis syndrome is a life-threatening complication of chemotherapy for patients with leukemia and large tumors with a high proliferative index, such as Burkitt's lymphoma. The syndrome is characterized by hyperkalemia, hyperphosphatemia, hypocalcemia, and hyperuricemia. The standard of care for hyperuricemia consists of hydration with or without alkalinization and administration of allopurinol. When treated in this manner, patients often experience persistent hyperuricemia that lasts several days after the start of antineoplastic therapy; sometimes they develop uric acid nephropathy as a consequence. Rasburicase, a recombinant urate oxidase enzyme, quickly removes large amounts of uric acid from plasma. The drug is approved by the United States Food and Drug Administration for management of elevated plasma uric acid levels in pediatric patients with leukemia, lymphoma, or solid tumor malignancies who are receiving chemotherapy. We undertook a retrospective review of adult patients treated with a single dose of rasburicase 6 mg for hyperuricemia associated with malignancy. Ten patients received one 6-mg dose of rasburicase, and one patient received two 6-mg doses as an adjuvant therapy to normalize uric acid levels. In most of the patients, a single 6-mg dose of rasburicase was effective in correcting uric acid levels in the typical time between diagnosis and start of antineoplastic therapy.

Related: Leukemia Cancer Prevention and Risk Reduction Rasburicase


Wang LY, Shih LY, Chang H, et al.
Recombinant urate oxidase (rasburicase) for the prevention and treatment of tumor lysis syndrome in patients with hematologic malignancies.
Acta Haematol. 2006; 115(1-2):35-8 [PubMed] Related Publications
In this multicenter, nonrandomized, open-label clinical trial conducted from July 2003 to July 2004, recombinant urate oxidase (rasburicase) was administered to patients at risk for tumor lysis syndrome before or during the initiation of chemotherapy. Forty-five patients were enrolled, including 18 children (10 with acute lymphoblastic leukemia, 6 with high-grade lymphoma, and 2 with acute myeloid leukemia) and 27 adults (8 with acute lymphoblastic leukemia, 4 with high-grade lymphoma, 9 with multiple myeloma, and 6 with acute myeloid leukemia). The age ranged from 3 to 98 years, with a median age of 7 years in children and 59.3 years in adults. There were 14 males and 4 females in the pediatric group and 18 males and 9 females in the adult group. Rasburicase 0.2 mg/kg was administered intravenously once a day for 2-6 days, for a median of 3 days in children and of 4 days in adults. After 3 days of treatment, the median uric acid levels in the 18 children decreased from 10.5 mg/dl (range 8-18.6) to 0.5 mg/dl (range 0.0-1.7). Similarly, in the 27 adults, the median levels decreased from 10.8 mg/dl (range 8-24.4) to 0.5 mg/dl (range 0.0-1.6). No significant changes were observed in serum potassium, calcium, and phosphorus concentrations. None of the patients required dialysis for acute renal failure. Rasburicase was very well tolerated, with only 1 adult having grade 1 vomiting. We conclude that rasburicase is safe and highly effective for preventing the complications of tumor lysis syndrome in patients with hematologic malignancies.

Related: Haematological Malignancies & Realted Disorders Leukemia Childhood Leukaemia Leukemia - Molecular Biology Non Hodgkin's Lymphoma Childhood Non-Hodgkin's Lymphoma NHL - Molecular Biology Rasburicase


Hummel M, Buchheidt D, Reiter S, et al.
Recurrent chemotherapy-induced tumor lysis syndrome (TLS) with renal failure in a patient with chronic lymphocytic leukemia - successful treatment and prevention of TLS with low-dose rasburicase.
Eur J Haematol. 2005; 75(6):518-21 [PubMed] Related Publications
INTRODUCTION: Rasburicase is a recombinant urate oxidase that is produced by a genetically modified Saccharomyces cerevisiae and has been approved for prophylaxis and treatment of tumor lysis syndrome in 2001. In several studies, rasburicase, given at a dose of 0.15-0.2 mg/kg for up to 7 d, proved to be highly effective in lowering urate levels.
CASE REPORT: We report the case of a patient with chronic lymphatic leukemia (CLL) who experienced tumor lysis syndrome (TLS) with acute renal failure after fludarabine/cyclophosphamide chemotherapy and after bendamustine treatment. During the first episode of TLS, after fludarabine/cyclophosphamide (creatinine 3.3 mg/dL, urate 24.6 mg/dL), the patient received rasburicase 0.2 mg/kg for 3 d. Urate levels decreased below the lower limit of normal and renal function recovered. After bendamustine therapy, given for disease progression 8 months later, TLS with acute oliguric renal failure re-occurred (creatinine 3.1 mg/dL, urate 20.8 mg/dL). The patient was treated with hyperhydration and two doses of rasburicase (0.056 mg/kg), resulting in a prompt decrease of the urate level and recovery of renal function. Both episodes of TLS were successfully treated with rasburicase in a lower dose than recommended by the manufacturer. During a second bendamustine course, TLS was successfully treated by low doses of rasburicase (0.056 mg/kg for 2 d).
CONCLUSION: This is the first report of TLS in CLL after bendamustine chemotherapy reported in the literature. Treatment and prevention of TLS by low doses of rasburicase is possible and cost-effective.

Related: Cyclophosphamide Chronic Lymphocytic Leukemia (CLL) CLL - Molecular Biology Bendamustine Rasburicase Fludarabine


Shin HY, Kang HJ, Park ES, et al.
Recombinant urate oxidase (Rasburicase) for the treatment of hyperuricemia in pediatric patients with hematologic malignancies: Results of a compassionate prospective multicenter study in Korea.
Pediatr Blood Cancer. 2006; 46(4):439-45 [PubMed] Related Publications
BACKGROUND: Hyperuricemia accompanying tumor lysis syndrome is a serious complication in neoplasia with rapid proliferation and destruction. To confirm the efficacy of recombinant urate oxidase (rasburicase) and its safety profile, a phase IV compassionate use prospective study was performed in Korean pediatric patients with hematologic malignancies.
PROCEDURE: Rasburicase was administered at 0.2 mg/kg/day once daily for 3-5 days (twice daily allowed during the first 72 hr) by intravenous route for hyperuricemia (uric acid > 7.5 mg/dl). The study period was 5 weeks and consisted of a baseline assessment within 48 hr before the administration of rasburicase, 3-5 days of assessment during treatment and a follow-up assessment at 4 weeks after its final administration.
RESULTS: The uric acid endpoint (< or =7.0 mg/dl) was reached in 97.3% (36/37) of the patients and uric acid levels were significantly reduced in all patients (P < 0.001). Drug related toxicities were mild and reversible without any grade 4 or serious adverse event associated with rasburicase.
CONCLUSION: This study confirms that rasburicase is a safe and effective agent for the treatment of hyperuricemia associated with hematologic malignancies in pediatric patients.

Related: Haematological Malignancies & Realted Disorders Rasburicase


Liu CY, Sims-McCallum RP, Schiffer CA
A single dose of rasburicase is sufficient for the treatment of hyperuricemia in patients receiving chemotherapy.
Leuk Res. 2005; 29(4):463-5 [PubMed] Related Publications
Hydration, urinary alkalization, and allopurinol are the standard of care in the treatment and prevention of hyperuricemia. Rasburicase is a new alternative for the management of hyperuricemia in cancer patients. Criteria for the use of rasburicase were developed by the Hematology/Oncology Pharmacy and Therapeutics Subcommittee of the Detroit Medical Center and implemented in 2003. The guidelines limit rasburicase use to one dose, with additional doses as needed, compared to the five doses recommended by the manufacturer, in cancer patients with hyperuricemia and bulky tumor who require immediate chemotherapy. During the period of March to September 2003, eight patients received rasburicase, according to the guidelines, for the management of hyperuricemia. One dose of rasburicase produced a rapid and sustained therapeutic effect of lowering the plasma uric acid levels in all patients. The levels remained below 4 mg/dL throughout the administration of chemotherapy for up to 96 h. Utilizing the guidelines resulted in a significant cost savings of 100,000 US dollars.

Related: Leukemia Childhood Leukaemia Leukemia - Molecular Biology Rasburicase


Tarella C, Bono D, Zanni M, et al.
Intensive chemotherapy in patients with lymphoma. Management of the risk of hyperuricemia.
Contrib Nephrol. 2005; 147:93-104 [PubMed] Related Publications
Intensive chemotherapy with stem cell autograft is a well-established salvage treatment for relapsed/refractory lymphoma patients aged less than 65 years and it is also an effective treatment option for high-risk patients at diagnosis. Clinical applicability of autograft has been greatly amplified by the use of peripheral blood progenitor cells (PBPC), whose administration is simple and feasible, and results in lower toxicity. In addition, the development of several prophylactic measures preventing extrahemopoietic toxicities has markedly improved the feasibility and tolerability of the approach. In particular, the risk of nephrotoxicity is no more a major problem in the autograft setting since the use of proper treatments for the management of hyperuricemia, including forced hydration along with urinary alkalinization and the administration of the recombinant urate oxidase drug rasburicase. The high-dose sequential (HDS) chemotherapy program is a typical example of an intensive chemotherapy with PBPC autograft. A 15-year experience with the HDS approach in 240 lymphoma patients is reported here. The results demonstrate the clinical efficacy of HDS, with prolonged survival both in relapsed/refractory patients (54% alive) and in those treated frontline (72% alive). In addition, a very low incidence of extrahemopoietic toxicities was observed. In particular, nephrotoxicity was almost abolished, with 2 patients displaying only mild and transient renal dysfunction. In conclusion, the reported results demonstrate the therapeutic efficacy of HDS in the treatment strategy for lymphoma and emphasize the importance of delivering intensive chemotherapy with all the prophylactic measures able to minimize nephrotoxicity and other potential extrahemopoietic toxicities.

Related: Stem Cell and Bone Marrow Transplants


Monitor
this page
it's private
powered by
ChangeDetection

This page last updated: 12th July 2014
Displaying links verified within last 2 weeks at time of update.

CancerIndex Logo

Home
Site Map
Cancer Types
Treatments
Locations
Glossary
Search

Patients/Public
Health Professionals
Researchers

About

Disclaimer
© 1996-2013