The value of low, fixed, single dose rasburicase in the prevention and treatment of tumor lysis syndrome.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e18558-e18558
Author(s):  
Bharadwaj Ponnada ◽  
Saadvik Raghuram ◽  
Sanketh Kotne ◽  
Pavithran Keechilat
Keyword(s):  
Uric Acid ◽  
Single Dose ◽  
Low Dose ◽  
Medical Center ◽  
Day Treatment ◽  
Tumor Lysis Syndrome ◽  
Urate Oxidase ◽  
Fixed Dose ◽  
Tumor Lysis ◽  
Prevention And Treatment

e18558 Background: Rasburicase is a recombinant urate oxidase drug approved by the US FDA for the management of hyperuricemia in Tumor Lysis Syndrome (TLS). Recommended dose of 0.2 mg/kg/day for 5 days is expensive and the benefit of extended schedule compared to a single fixed dose of 1.5 mg is not known. Methods: This is a retrospective cohort study done at a tertiary medical center including 165 (144 adult and 21 pediatrics) patients admitted between January 2013 and December 2018. We analyzed the efficacy of single low dose rasburicase 1.5 mg irrespective of bodyweight in adults and in children a dose of 0.15 mg/kg (maximum 1.5 mg) intravenously over 30 min for prevention and treatment of TLS and subsequent doses were given based on clinical and biochemical response. Plasma samples for uric acid were collected at baseline, 6–24 hrs, 48 hrs post-rasburicase, and daily during treatment. The primary outcome was achieving a uric acid level less than 7.0 mg/dl after a single dose of rasburicase in the groups. Secondary outcomes included need for repeat rasburicase doses, and a cost analysis. Results: Children accounted for 12.1% (n = 20) and adults 87.9% (n = 145). The median ages in pediatric and adult groups were 7.9 years and 54 years respectively. Rasburicase was used prophylactically in 35 (21.2%), for laboratory TLS in 105 (63.6%) and for clinical TLS in 25 (15.2%) patients. SDR prevented laboratory/clinical TLS in 89% of the prophylactic group and prevented clinical TLS in 72% of the laboratory TLS group. However, 92%(n=23) of the patients with clinical TLS required more than one dose rasburicase. The average total monthly cost of rasburicase was reduced by 96% ($2850 to $114) after adoption of the above protocol. Conclusions: Single low dose rasburicase is a highly economical and clinically effective way of managing patients with TLS and could serve as an alternative to the 5-day treatment. This dose, therefore, balances cost and efficacy of treatment.

Single 6-mg dose of rasburicase: The experience in a large academic medical center

2018 ◽  
Vol 25 (6) ◽  
pp. 1349-1356 ◽  
Author(s):  
Mary Nauffal ◽  
Robert Redd ◽  
Jian Ni ◽  
Richard M Stone ◽  
Daniel J DeAngelo ◽  
...  
Keyword(s):  
Uric Acid ◽  
Lactate Dehydrogenase ◽  
Serum Creatinine ◽  
Medical Center ◽  
Academic Medical Center ◽  
Tumor Lysis Syndrome ◽  
Urate Oxidase ◽  
Baseline Serum ◽  
Tumor Lysis ◽  
Blood Ph

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.

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

2018 ◽  
Vol 25 (3) ◽  
pp. 577-583 ◽  
Author(s):  
Alyssa Boutin ◽  
Alison Blackman ◽  
David M O’Sullivan ◽  
Nicholas Forcello
Keyword(s):  
Uric Acid ◽  
Single Dose ◽  
Drug Administration ◽  
Uric Acid Level ◽  
Acid Level ◽  
Low Dose ◽  
Food And Drug Administration ◽  
Tumor Lysis Syndrome ◽  
Tumor Lysis ◽  
Treatment And Prevention

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.

scholarly journals A Phase II Non-Randomized Study to Evaluate the Efficacy of Single Dose Rasburicase (1.5mg) in Adult Acute Leukemia and High Grade Lymphomas with Established Tumor Lysis Syndrome

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2914-2914
Author(s):  
Jayshree Thorat ◽  
Swaratika Majumdar ◽  
Hasmukh Jain ◽  
Avinash Bonda ◽  
Lingaraj Nayak ◽  
...  
Keyword(s):  
Uric Acid ◽  
Single Dose ◽  
Adverse Events ◽  
Acute Leukemia ◽  
Tumor Lysis Syndrome ◽  
Fixed Dose ◽  
High Grade ◽  
Blood Samples ◽  
Tumor Lysis ◽  
Plasma Uric Acid

BACKGROUND Tumor lysis syndrome (TLS) refers to a constellation of metabolic derangements due to the breakdown of tumor cells.It is a medical emergency and is associated with significant morbidity and mortality. Hyperuricemia is a key manifestation of TLS, that can lead to renal insufficiency and trigger a vicious cycle of metabolic abnormalities. Rapid resolution of hyperuricemia is key to successful outcomes. Rasburicase is a recombinant form of enzyme urate oxidase, approved in patients with established TLS,which converts the uric acid to soluble allantoin. It acts rapidly, bringing down the levels in as less as 4 hours. The approved dose is 0.2 mg/kg/day for 5 days. While there is efficacy data to support the use of fixed low-dose (1.5-3 mg) rasburicase in the prophylactic setting,no such data exists in the therapeutic setting. Each 1.5 mg vial costs about 8,000 rupees (115 USD), the dose required for a 60 kg adult would be 12 mg, which equals to about 300,000 rupees (4340 USD) for 5 days. Given the cost constraints, most of our patients with established TLS receive only a single fixed dose of rasburicase at 1.5 mg as a standard of care. We have observed that even this lower dose is adequate to normalize the uric acid levels in a majority of them. We planned to prospectively evaluate the efficacy of single-dose rasburicase in patients with established TLS. METHODS We conducted a single centre phase II study and enrolled patients (>15 years) with de-novo acute leukemia and high-grade lymphoma with hyperuricemia(laboratory or clinical TLS) and ECOG PS ≤ 4. Patients with hemodynamic instability or neurological impairment were excluded. After enrollment, patients received rasburicase at a dose of 1.5 mg fixed-dose intravenous over 30 min. Patients were monitored daily either as an in- or outpatient. Blood samples to measure the renal function tests and electrolytes were collected at 4 hours, 24-h, 48-h, Day 3, Day 4, and Day 5. Blood samples were transported in heparinized tubes at room temperature and processed immediately. Additional 1.5 mg dose of rasburicase was given if the plasma uric acid level did not decline by at least 50% at 24 hours. Additional doses were also given at the clinician's discretion in case of rising uric acid levels on subsequent monitoring. The primary objective was to estimate the rate of plasma uric acid response (Defined as normalization of uric acid at 48 hours that is sustained till day 5). Secondary objectives were to assess the number of patients requiring additional doses of rasburicase, need for dialysis, mortality attributable to TLS and adverse events due to rasburicase. The sample size was calculated using Simon's two-stage design.52 patients were required to detect a Plasma UA response rate of 85% (Compared to 99% with the approved dose) with a type I error of 5% and power of 80%. Due to a higher than anticipated attrition rate, we enrolled 70 patients. Results: A total of 70 patients were enrolled in the study, 60 were analyzed for secondary and 53 for the primary endpoint (Fig 1). The baseline features are summarized.(Fig 1) Plasma uric acid normalized at 48 hours in 37/53 (70%) of the patients and became normal at day 5 in 46/53(87%) of the patients. The corresponding figures for the entire cohort were 68% and 82% respectively. Only 3 patients required hemodialysis. 11 patients were managed as outpatient, the remaining were admitted. 3 patients required ICU admission. 20 patients required additional doses of rasburicase, out of which 13 patients required 2 doses, 5 patients required 3 doses, 1 each required 4 and 5 doses. The total number of vials required in the study were 83 vials. In comparison, 2120 vials would have been required for a cohort of people weighing 60kgs. Hypersensitivity reaction, cardiac dysfunction, methemoglobinemia were not seen in any patient. 1 patient developed hemolysis post rasburicase. Other adverse events were fever(25%), vomiting(10%), abdominal pain(13%). All 60 evaluable patients were alive at the end the study. Conclusion: Lower dose of rasburicase is sufficient and cost-effective in established TLS. This strategy obviates the need for FDA approved higher doses. Disclosures No relevant conflicts of interest to declare.

Follow-Up Study on Management of Tumour Lysis Syndrome with Single Low Fixed Dose (1.5 mg) of Rasburicase - A Tertiary Cancer Centre Experience from India

2021 ◽  
Vol 8 (25) ◽  
pp. 2149-2154
Author(s):  
Alok Ranjan ◽  
Nisha Khanna ◽  
Vivek Ranjan ◽  
Ashwin Kumar
Keyword(s):  
Uric Acid ◽  
Single Dose ◽  
Tumour Lysis Syndrome ◽  
Urate Oxidase ◽  
Fixed Dose ◽  
Additional Dose ◽  
Tumour Lysis ◽  
Follow Up Study ◽  
Study Results

BACKGROUND Rasburicase (recombinant urate oxidase) has been proven to be an effective therapy for prevention of tumour lysis syndrome (TLS). The recommended daily dosing regimen of rasburicase is 0.2 mg/kg/day for 5 days which is expensive and unaffordable to many patients in the developing countries. The purpose of the present study was to evaluate the effect of single 1.5 mg dose rasburicase in the management of tumour lysis syndrome. METHODS This is a follow-up study done at our institute. Fifty (50) patients with tumour lysis syndrome who received rasburicase from August 2015 to January 2020 were enrolled in this study RESULTS Single dose of rasburicase is effective in decreasing serum uric acid level in significant number (N = 41) of patients. Percentage of patients having uric acid less than 7 mg after single dose of rasburicase in 48 hours - 82.9 % (N = 34) while 17 % (N = 7) were found to have uric acid levels of more than 7 mg/dl. The percentage of patients with uric acid levels more than 7 mg/dl reduced from 36.5 % after 24 hours to 17 % after 48 hours. This indicates that the uric acid levels show a declining trend even after 24 hours without giving an additional dose of rasburicase. There was no relationship between uric acid levels at 24 hours and percentage change in creatinine level from baseline to 24 hours (correlation coefficient (r) = -0.047, P = 0.770. Patients who required additional dose (N = 9) had high base line value of uric acid and their high value was maintained over the follow up period of three days. Patients with pre exiting kidney disease and high level of baseline uric acid also needed dialysis (N = 3). CONCLUSIONS In majority of patients, a single 1.5 mg dose of rasburicase is an effective way to reduce raised uric acid in appropriate circumstances. KEYWORDS Single Dose, Recombinant Urate Oxidase, Uric Acid, Leukemia, Tumour Lysis Syndrome, Rasburicase

scholarly journals A Comparison of Single Dose Rasburicase 3 Mg Versus 6 Mg for the Management of Tumor Lysis Syndrome

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4511-4511
Author(s):  
Sarah K Kraus ◽  
Catherine E Burdalski ◽  
Colleen Timlin ◽  
Tracy M Krause ◽  
Todd A Miano ◽  
...  
Keyword(s):  
Single Dose ◽  
Research Funding ◽  
Hematological Malignancies ◽  
Tumor Lysis Syndrome ◽  
Wholesale Price ◽  
Cost Savings ◽  
Urate Oxidase ◽  
Categorical Variables ◽  
Tumor Lysis ◽  
Dosing Strategies

Abstract Introduction: Rasburicase, a recombinant form of urate oxidase, is a highly effective treatment for tumor lysis syndrome (TLS). Although the FDA-approved dose for rasburicase is 0.2 mg/kg/day for up to five days, many centers have adopted alternative dosing strategies to decrease cost, the most common being a single 6 mg dose. We hypothesized that further reducing the dose to 3 mg would result in similar efficacy and yield significant cost savings compared to the 6 mg dose strategy. Methods: We conducted a retrospective cohort study to examine the comparative effectiveness of a single 3 mg dose of rasburicase versus a single 6 mg dose in 108 adults with hematological malignancies presenting with a baseline uric acid (UA) ≤ 12 mg/dL between June 2009 and February 2015. Prior to January 2012, our institutional policy recommended a single 6 mg dose for all patients who met criteria for rasburicase for TLS. In January 2012, the policy was amended to recommend a single 3 mg dose for patients with a baseline UA ≤ 12 mg/dL. Thus, the study included 56 patients with UA ≤ 12 who received a single 6 mg dose prior to the policy modification and 52 patients with UA ≤ 12 given the 3 mg dose after the amendment. The primary endpoint was the percentage of patients who achieved a UA ≤ 8 mg/dL (the upper limit of normal at our institution) 24 hours after a single dose of rasburicase. Fisher's exact test was used to analyze categorical variables and t-tests were used to analyze continuous variables. The a priori level of significance was set at α < 0.05. Results: The mean baseline UA was 9.3 mg/dL and 9.8 mg/dL in the 3 mg arm and 6 mg arm, respectively (P = .19). At 24 hours there was no difference in the percentage of patients who achieved a UA ≤ 8 mg/dL (92% vs. 98%; P = 0.36). In addition, there was no difference in the percentage of patients who achieved a UA ≤ 8 mg/dL at 48 hours (98% vs. 100%; P = 0.48). Six (11.5%) patients in the 3 mg arm and one (1.8%) patient in the 6 mg arm required a second dose of rasburicase to achieve a UA <8 mg/dL (P = 0.1). Of note, the 6 mg group had a greater percent reduction in UA from baseline compared to the 3 mg group at both 24 hours (-68.1% vs. -48.6%; P < .01) and 48 hours (-69.3% vs. -51.3%; P = 0.02) after rasburicase administration. There was no difference in the percent change of serum creatinine between the two dosing strategies at 24 hours (-6.5% vs. 0.1%; P = 0.11) or 48 hours (-4.5% vs. -2.5%; P = 0.22). In addition, no difference was observed with respect to the percent of patients who required renal replacement therapy within 7 days of rasburicase administration (8.9% vs. 9.6% P = 1.0). Based on the average wholesale price of $815 for one 1.5 mg vial of rasburicase, the single 3 mg dose was associated with approximately $1,500 cost savings per encounter compared to the 6 mg dose. Conclusion: A single 3 mg dose of rasburicase was as effective as 6 mg in normalizing UA within 24 hours. Our findings demonstrate that administering a single 3 mg dose of rasburicase is a cost-effective alternative for TLS management in patients with hematological malignancies presenting with a UA ≤ 12 mg/dL. Disclosures Svoboda: Immunomedics: Research Funding; Celgene: Research Funding; Seattle Genetics: Research Funding; Celldex: Research Funding. Ganetsky:Onyx: Speakers Bureau.

scholarly journals Efficacy of Fixed Low Dose Rasburicase in the Prevention and Treatment of Tumor Lysis Syndrome

2015 ◽  
Vol 0 (0) ◽  
pp. 46 ◽  
Author(s):  
Remya Antony ◽  
Sandhya Lakshmi ◽  
Akhila Sivadas ◽  
Wesley M. Jose ◽  
Neeraj Sidharthan ◽  
...  
Keyword(s):  
Low Dose ◽  
Tumor Lysis Syndrome ◽  
Tumor Lysis ◽  
Prevention And Treatment

Randomized Clinical Trial of Rasburicase Administered as a Standard Fixed Five Days Dosing Vs a Single Dose Followed by as Needed Dosing in Adult Patients with Hematologic Malignancies at Risk for Developing Tumor Lysis Syndrome.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 105-105 ◽  
Author(s):  
Saroj Vadhan-Raj ◽  
Luis Fayad ◽  
Michelle Fanale ◽  
Barbara Pro ◽  
Alma Rodriguez ◽  
...  
Keyword(s):  
Uric Acid ◽  
Single Dose ◽  
High Risk ◽  
Serum Creatinine ◽  
Plasma Levels ◽  
Pediatric Patients ◽  
Tumor Lysis Syndrome ◽  
Hematologic Malignancies ◽  
Tumor Lysis ◽  
Tnf Α

Abstract Abstract 105 Tumor lysis syndrome (TLS) is a potentially life threatening complication resulting from massive lysis of malignant cells and most frequently observed in patients with rapidly proliferating, bulky, and chemo-sensitive malignancies. The prevention and management of TLS includes hydration and reduction in the levels of serum uric acid by drugs that decrease production or increase excretion of uric acid. Rasburicase is a recombinant urate oxidase that rapidly reduces the levels of uric acid by enhancing the conversion of existing uric acid into allantoin which is more soluble in urine than uric acid. Rasburicase is approved in the USA for the treatment of pediatric patients at high risk for developing TLS, to be administered at a dose of 0.15 to 0.2 mg/kg once daily for 5 days. Although, activity has been seen with lower doses and shorter duration of treatment, the optimal dosing of rasburicase has not been established for adults. The purpose of this study was to evaluate the efficacy of rasburicase (0.15 mg/kg) administered as a single dose followed by as needed (max 5 doses over 5 days) as compared to standard fixed 5-days dosing in patients with hematologic malignancies at risk for TLS. The patients were stratified based on their risk for TLS and randomized 1:1 to rasburicase administered as a single dose followed by as needed (Arm A) or fixed daily dose x 5 days (Arm B). Sixty six patients were enrolled; 20 had > 2-fold LDH levels and 9 had above-normal serum creatinine. 64 patients received at least one dose of rasburicase and were evaluable for response [24 high risk with mean baseline uric acid levels, 9.8 (7.6–16.1 mg/dL) and 40 potential risk with uric acid, 5.3 (2.4-7.4 mg/dL)]. All patients normalized their uric acid levels at 4 hours after the first dose; 83% to an undetectable level (<0.7 mg/dL). On Arm B (fixed 5-days dosing), all patients (n=34, 100%) had a sustained response, as defined by the normalization of uric acid levels in 48 hours and its maintenance within normal range for 6 days. On Arm A, all except for 4 patients (all 4 high risk for TLS) had a sustained response (26 of 30, 87%) to a single dose of rasburicase. Four of 11 patients from the high risk group required a second dose around day 4 for uric acid levels >7.5 mg/dL. Serum creatinine normalized in all patients by day 5. The treatment was well tolerated, except for one incident of methemoglobinema and hemolytic anemia in a patient found to have G6PD deficiency. Since high uric acid levels have been associated with elevated cytokine levels, we examined the effects of treatment on plasma cytokines. At baseline, high risk patients showed increased TNF-α and IL-6 plasma levels. There was a marked decrease in the plasma levels of TNF-α (from mean 14.2 to 6.4 pg/ml, p<0.0001), and IL-6 (from 11.2 to 8 pg/mL, p=0.05) during treatment. Conclusion: Rasburicase is a highly effective uricolytic agent for prevention and management of TLS. This study demonstrates that it is feasible to decrease the duration of administration of rasburicase at the approved dose of 0.15 mg/kg. The majority of patients responded to a single dose of the agent, and only a small subset at high risk for TLS required a second dose. Disclosures: Vadhan-Raj: Sanofi Aventis: Honoraria, Research Funding. Off Label Use: Rasburicase is indicated for the initial management of plasma uric acid levels in pediatric patients with leukemia, lymphoma, and solid tumor malignancies who are receiving anti-cancer therapy expected to result in tumor lysis and subsequent elevation of uric acid. The approved administration dose, route, and schedule are 0.15-0.20 mg/kg IV infusion for 5 days, respectively.

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