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.

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-Dose Rasburicase Might Be Adequate To Overcome Tumor Lysis Syndrome In Hematological Malignancies

2021 ◽  
Author(s):  
Samet Yaman ◽  
Semih Başcı ◽  
Gökhan Turan ◽  
Bahar Uncu Ulu ◽  
Tuğçe Nur Yiğenoğlu ◽  
...  
Keyword(s):  
Single Dose ◽  
Hematological Malignancies ◽  
Tumor Lysis Syndrome ◽  
Tumor Lysis

Superiority of Rasburicase Versus Allopurinol on Serum Uric Acid Control in Adult Patients with Hematological Malignancies at Risk of Developing Tumor Lysis Syndrome : Results of a Randomized Comparative Phase III Study.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 919-919 ◽  
Author(s):  
Jorge Cortes ◽  
Karen Seiter ◽  
Richard Thomas Maziarz ◽  
Meir Wetzler ◽  
Michael Craig ◽  
...  
Keyword(s):  
At Risk ◽  
Uric Acid ◽  
Adverse Events ◽  
Serum Uric Acid ◽  
Hematological Malignancies ◽  
Tumor Lysis Syndrome ◽  
Urate Oxidase ◽  
Phase Iii ◽  
Tumor Lysis ◽  
Phase Iii Study

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.

Single Use of Rasburicase (rasb) Leads to Insufficient Tumor Lysis Syndrome (TLS) Control in Adults: Outcome and Resource Utilization in a One Year Real-Life Observational Study

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4694-4694
Author(s):  
Matthaeus Krych ◽  
Julia Ostermann ◽  
Wolfgang Hiddemann ◽  
Helmut Ostermann
Keyword(s):  
Single Dose ◽  
Observational Study ◽  
Tumor Lysis Syndrome ◽  
Real Life ◽  
Treatment Costs ◽  
University Hospital ◽  
Urate Oxidase ◽  
Tumor Lysis ◽  
The Mean ◽  
One Year

Abstract TLS due to the rapid lysis of tumor cells following initiation of chemotherapy can lead to the release of intracellular components into the extracellular space. Among these hyperuricemia might exceed the excretory capacity of the kidneys and lead to renal failure. Rasb is a recombinant urate oxidase given during the first 3–5 days of chemotherapy to effectively lower uric acid serum levels. Limited data suggest that a single prechemotherapy dose of rasb might be sufficiently efficacious and this single dose regimen is widely used to reduce treatment costs. We analyzed the clinical and economical data of all adults who received rasb for prophylaxis or treatment of TLS at a university hospital during a one year period. The goal was to describe treatment patterns and outcome outside of clinical trials and to verify whether patients with TLS can be treated cost-effectively. 38 patients (pts) received rasb, however 1/3 of the pts were treated off-label for other reasons then TLS. 24 pts (median age 66 yrs, 21 male) received rasb for malignancy-associated hyperuricemia and were eligible for further clinical and economical evaluation. 2/3 of these pts were treated for hematological malignancies (acute leukemia 6pts, lymphoma 8 pts) and 8 pts for solid tumors. Apart from hydration (mean volume 2 l per day; all pts), furosemide (mean dose 80 mg/day; all pts) and urinary alkalinization with sodium bicarbonate (pH &gt; 7; 7 pts), 20 patients received a single 7,5 mg dose of rasb and 4 pts received multi dose. In 14 pts a tumor lysis was observed. 6 pts died, three fatalities were directly associated with TLS. Mortality was higher among pts with single dose rasb vs. multi dose rasb (30% vs. 0 %) and higher among patients with urinary alkalinization (71% vs. 5%). No anaphylaxis, hemolysis or methemoglobinemia was observed in this cohort. The mean duration of hospitalisation was 23 days, the mean treatment costs were 16.200 €. The costs exceeded the revenues based on diagnosis related groups for Germany (G-DRG) in 18 pts and resulted in a 7% funding gap. 107.000 € were spent for drugs for these patients, 10% of these for rasb. We conclude from this observational study that TLS is a menacing disease, resulted in a 12,5 % mortality and should therefore be cautiously monitored and treated, single dose rasb was associated with a higher mortality rate then multi dose, urinary alkalinization cannot be recommended when rasb is used, TLS leads to a 7 % underfunding in the respective G-DRGs, for TLS pts. the usage of rasb elevates the total drug expenses by 10%.

BPI19-016: Evaluation of the Use of a Single Dose Rasburicase in Prophylaxis and Management of Tumor Lysis Syndrome (TLS) Among Cancer Patients in Qatar

2019 ◽  
Vol 17 (3.5) ◽  
pp. BPI19-016
Author(s):  
Nancy Kassem ◽  
Halima El Omri ◽  
Mohamed Yassin ◽  
Shereen Elazzazy
Keyword(s):  
Single Dose ◽  
Tumor Lysis Syndrome ◽  
Lactate Dehydrogenase Level ◽  
Primary Objective ◽  
Urate Oxidase ◽  
Multiple Doses ◽  
Oxidase Enzyme ◽  
Secondary Objective ◽  
Significant Cost Reduction ◽  
The Impact

Introduction: Rasburicase is a urate oxidase enzyme used for prophylaxis and treatment of hyperuricemia associated with TLS. The recommended dose of rasburicase is 0.2 mg/kg/day for 5 days; however, recent studies have demonstrated the effectiveness of a single rasburicase dose in prophylaxis and management of hyperuricemia associated with TLS. Our institution’s TLS guideline was updated to recommend the use of a single rasburicase dose (0.2 mg/kg). The primary objective of this study was to assess the efficacy of a single rasburicase dose in controlling uric acid (UA); the secondary objective was to evaluate the impact of the institutional TLS guidelines update on consumption and cost of rasburicase. Methods: This is a single center retrospective cohort study including all patients who received rasburicase from August 2012 to March 2016 at the National Center for Cancer Care and Research (NCCCR) in Qatar. Patients were divided into 2 groups based on the prescribed number of rasburicase doses (single dose vs multiple doses). Collected data included patients’ diagnosis, laboratory parameters rasburicase dose, duration, and number of dispensed vials. UA levels within 24 hours and on day 5 of initial rasburicase dose were evaluated. Risk stratification was determined according to institutional guidelines based on disease, white blood cell count, lactate dehydrogenase level, renal function, and UA level. Results: A total of 103 patients who received rasburicase were evaluated retrospectively; rasburicase was prescribed as single dose for 65 patients (63%) and multiple doses for 38 patients (37%). The majority of patients who received rasburicase as single or multiple doses were at high risk of developing TLS, representing 68% and 84%, respectively. Baseline mean UA levels were similar in both groups: 5.4±2.9 mg/dL vs 4.7±3.2 mg/L respectively (P=.7). Normal or undetectable UA levels were observed within 24 hours in 98% of patients in the single dose group and 100% of patients in the multiple doses group. All patients in both groups had normal UA on day 5 of rasburicase with relatively similar UA levels: 1.5±1.2 mg/dL vs 0.8±1 mg/dL (P=.18). Rasburicase consumption and cost were reduced by 42.5% after the guidelines update. Conclusion: The single rasburicase dose demonstrated efficacy in controlling serum UA levels. Updating the institutional TLS guidelines had a significant impact on rasburicase consumption and led to significant cost reduction.

Phase I Trial of Bortezomib (PS-341; NSC 681239) and Alvocidib (Flavopiridol; NSC 649890) in Patients with Recurrent or Refractory Indolent B-Cell Neoplasms - Update of the “Bolus” Infusion Schedule of Alvocidib.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2959-2959
Author(s):  
Beata Holkova ◽  
Edward B. Perkins ◽  
Prithviraj Bose ◽  
Daniel M Sullivan ◽  
Rachid Baz ◽  
...  
Keyword(s):  
Febrile Neutropenia ◽  
Research Funding ◽  
Phase I Trial ◽  
Cell Lymphoma ◽  
Tumor Lysis Syndrome ◽  
Tumor Lysis ◽  
Mantle Cell ◽  
Infusion Schedule ◽  
Grade 3 ◽  
Dose Levels

Abstract Abstract 2959 Preclinical studies suggest that neoplastic cells may be particularly sensitive to simultaneous interruption of cell cycle and survival signaling pathways. We have previously reported that the cyclin-dependent kinase inhibitor alvocidib interacts with bortezomib, a proteasome inhibitor, to induce mitochondrial injury and apoptosis in human leukemia, myeloma, and lymphoma cells (Dai et al, Oncogene 22:7108, 2003; Dai et al, Blood 104:509, 2004). These actions were associated with inhibition of NF-κB DNA binding, increased expression of pJNK, and down-regulation of XIAP and Mcl-1. Based on these findings, a phase I trial was initiated in which bortezomib was administered in conjunction with alvocidib on the same days, according to 2 separate schedules: a “hybrid” infusion schedule (half the dose over 30 minutes and half over a 4-hour infusion); and a bolus infusion schedule in which alvocidib was administered over 1 hour. Results of the hybrid infusion schedule have recently been reported (Holkova et al, Clin Cancer Res 17:3388, 2011). The primary objective was to identify the maximum tolerated doses (MTDs) for the combination in the treatment of recurrent or refractory indolent B-cell neoplasms. Eligible patients included those with multiple myeloma (MM) or non-Hodgkin's lymphoma (NHL), with recurrent or refractory disease following at least 1 prior systemic therapy. To date, 43 patients have been treated at 9 dose levels. Patients with the following disease types have been treated: MM n=25 (Waldenstrom's macroglobulinemia n=2), NHL n=18 (mantle cell lymphoma n=5). The male:female ratio was n = 31 (72%):12 (28%); the median age was 65 (range: 40–79) years; ECOG performance scores ranged from 0–1; and the median number of prior therapies was 3 (range: 1–10). The schedule of administration was bortezomib via intravenous push over 3–5 seconds followed by alvocidib via intravenous 1-hour infusion on days 1, 4, 8, and 11; on a 21-day cycle, with indefinite continuation for responding patients and those with stable disease. Adverse events (AEs) were evaluated using CTCAE version 4. Dose limiting toxicities (DLTs) observed to date are shown in Table 1. Grade 3 and 4 AEs possibly, probably, or definitely related to study treatment tht occurred in ≥ 5% of patients were dehydration (7%), diarrhea (19%), fatigue (16%), febrile neutropenia (5%), leukopenia (37%), lymphopenia (28%), neutropenia (58%), peripheral neuropathy (12%), and thrombocytopenia (44%). No grade 5 events were observed. One patient developed tumor lysis syndrome and required hospitalization for 48 hours with complete recovery. Common grade 2 AEs possibly, probably or definitely related to treatment were anemia (30%), anorexia (28%), diarrhea (47%), fatigue (60%), leukopenia (47%), lymphopenia (28%), and thrombocytopenia (56%). Of the 43 patients treated, 38 have been evaluable for response. Patient responses are shown in Table 2. Correlative studies examining expression of pJNK, Mcl-1, XIAP, PARP, and NFκB are being collected for processing at the end of the study. Collectively, these findings indicate that the combination of bortezomib and alvocidib, the latter administered as a 1-hour infusion, is tolerable. The regimen appears active in patients with relapsed and/or refractory MM or NHL, justifying phase II studies to determine the activity of this regimen more definitively. The MTD has not yet been reached. Table 1. Dose levels and DLTs Dose Level Bortezomib (mg/m2) Alvocidib (mg/m2) Patients treated/# DLTs DLT 1 1.0 15 3/0 2 1.3 15 5/0 3 1.3 22 3/0 4 1.3 30 3/0 5 1.3 40 7/1 Grade 3 back pain 6* 1.3 50 5/1 Grade 3 fatigue 7** 1.3 60 8/2 Grade 3 febrile neutropenia Grade 3 tumor lysis syndrome 8** 1.3 75 6/2 Grade 3 diarrhea Grade 3 esophagitis/oral mucositis 9** 1.3 90 3/2 Grade 3 febrile neutropenia Grade 4 absolute neutrophil count decrease * Study is currently enrolling to dose level 6 ** Exceeded MTD Table 2. Response by diagnosis NHL MM Total (n = 15) (n = 23) (n = 38) Complete Remission 2b,c 1a 3 Partial Remission 3 7d,e 10 Complete + Partial Remission N(%) 5 (33) 8 (35) 13 (34) a Includes 1 patient with prior bortezomib b Includes 1 patient with prior autologous SCT c Includes 1 patient with mantle cell lymphoma d Includes 1 patient with Waldenstrom's macroglobulinemia e Includes 1 patient still under active treatment Disclosures: Baz: Celgene: Research Funding; Millennium: Research Funding; Bristol Myers Squibb: Research Funding; Novartis: Research Funding.

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