Single-Dose Rasburicase 6 mg in the Management of Tumor Lysis Syndrome in Adults

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1 Single-Dose Rasburicase 6 mg in the Management of Tumor Lysis Syndrome in Adults Anne M. McDonnell, Pharm.D., Kristi L. Lenz, Pharm.D., Debra A. Frei-Lahr, M.D., John Hayslip, M.D., and Philip D. Hall, Pharm.D. Rasburicase is currently approved at a dosage of mg/kg once/day for 5 days in pediatric patients with cancer to lower plasma uric acid concentrations and manage tumor lysis syndrome (TLS). Information on rasburicase dosing in adults is limited, with some data on using rasburicase as a single dose instead of multiple daily doses. Therefore, we evaluated the efficacy of a single dose of rasburicase for preventing or managing TLS in adults. We collected retrospective data for 11 adults with hematologic malignancies who received a single 6-mg dose of rasburicase. All patients received intravenous hydration with urinary alkalinization and allopurinol; however, due to adverse reactions, two patients received short courses of allopurinol. Only patients at high risk for TLS (e.g., large tumor burden, increasing uric acid concentration) or those with TLS received rasburicase. The single dose of rasburicase 6 mg resulted in a median mg/kg dose (range mg/kg). The single 6-mg dose rapidly lowered uric acid concentrations in 10 of the 11 patients. The median uric acid concentration of 11.7 mg/dl (range mg/dl) declined to 2.0 mg/dl (range mg/dl) within a day after rasburicase administration (p=0.022). In these 10 patients, uric acid concentrations remained low despite subsequent chemotherapy, and none required additional rasburicase doses. The only patient who did not respond to the single 6-mg rasburicase dose was a morbidly obese man (259 kg, body mass index 87 kg/m 2 ) who subsequently responded to an additional dose of rasburicase 12 mg. These results warrant further investigation of a single 6-mg dose of rasburicase in adults with TLS or at high-risk for developing TLS. Key Words: rasburicase, lymphoma, leukemia, tumor lysis syndrome, uric acid. (Pharmacotherapy 2006;26(6): ) From the Department of Pharmacy Services, Medical University Hospital (Dr. McDonnell), the Department of Pharmacy and Clinical Sciences, South Carolina College of Pharmacy (Drs. Lenz and Hall), the Department of Medicine, College of Medicine (Drs. Frei-Lahr and Hayslip), and Hollings Cancer Center (Drs. Frei-Lahr and Hall), Medical University of South Carolina, Charleston, South Carolina. Address reprint requests to Philip D. Hall, Pharm.D., Department of Pharmacy and Clinical Sciences, South Carolina College of Pharmacy, Medical University of South Carolina Campus, 280 Calhoun Street, Box , Charleston, SC Tumor lysis syndrome (TLS) occurs as a result of rapid malignant cell lysis and is manifested by electrolyte abnormalities such as hyperkalemia, hyperphosphatemia, hypocalcemia, and hyperuricemia. It may occur spontaneously or be precipitated by chemotherapy, corticosteroids, radiation, hormonal agents, or biologic response modifiers. Tumor lysis syndrome is most profound in the presence of rapidly proliferating tumors, chemosensitive disease, or malignancies with a high tumor burden. The hyperuricemia of

2 SINGLE-DOSE RASBURICASE IN ADULTS McDonnell et al TLS results when purine nucleic acids are released by tumor cell lysis and metabolized into uric acid. At high concentrations, uric acid can precipitate and form an obstructive nephropathy, contributing to acute renal failure. Some patients may require dialysis secondary to hyperuricemia and its subsequent electrolyte abnormalities. 1, 2 Prevention of TLS requires aggressive hydration with urinary alkalinization and allopurinol, with the goal of minimizing electrolyte abnormalities and uric acid induced nephropathy. Allopurinol has been available in the United States since 1966 and is effective in the prophylactic management of hyperuricemia by inhibiting xanthine oxidase. Allopurinol has no effect on existing uric acid. Rasburicase is a recombinant urate oxidase approved by the United States Food and Drug Administration (FDA) in It is indicated for prevention of hyperuricemia in children with malignancies that have a high occurrence of TLS. Rasburicase catalyzes the breakdown of uric acid into allantoin and hydrogen peroxide. Allantoin is up to 10 times more soluble than uric acid and has a decreased rate of precipitation in the renal tubules. 3 Currently, rasburicase is FDA approved at a dosage of mg/kg once/day for 5 days in pediatric patients to lower plasma uric acid concentration and manage TLS. 4 Limited data are available regarding rasburicase use in adults. The largest trial was the Groupe d Etude des Lymphomes de l Adulte Trial on Rasburicase Activity in Adult Lymphoma study (GRAAL1). 5 In this trial, 100 adult patients with non-hodgkin s lymphoma received rasburicase 0.2 mg/kg/day for 3 7 days, starting either the day before or the first day of chemotherapy. Of these patients, 95 who received three or more doses responded to rasburicase, resulting in decreased uric acid concentrations. All patients maintained low uric acid concentrations throughout treatment. In several small case series, a single dose of rasburicase was administered as an alternative to multiple daily doses in children. In one report, three children with newly diagnosed leukemia were treated with a single, fixed dose of rasburicase 4.5 mg (range mg/kg) before the start of chemotherapy to prevent TLS. 6 None of the three experienced hyperuricemia after the single dose, and none required dialysis. In another case series, four adults received rasburicase for management of hyperuricemia secondary to TLS. 7 Doses ranged from mg (range mg/kg) for one to three doses. Uric acid concentrations were successfully lowered in all four patients. In a third series, a single dose of rasburicase 0.15 mg/kg was administered to two children and six adults with hematologic malignancies. 8 In all patients, rasburicase caused a rapid and sustained lowering of serum uric acid concentrations, and no patient required dialysis. Because of the limited information and the promising results in adults given a single dose of rasburicase, we evaluated the use of a single-dose strategy in adult patients. Also, because of the high cost of rasburicase, the single, fixed dose may be cost-effective. We describe our experience with the administration of a single dose of rasburicase 6 mg in 11 adults with advanced hematologic malignancies. We chose the 6-mg fixed dose for our first patient (72.7 kg) based on the lowest effective milligram/kilogram dose (0.08 mg/kg) used in one of the case series discussed above. 6 Methods We selected the patients for this series by searching the pharmacy database and identifying cases known to us. All uric acid concentrations were stored in ice when they were sent to the laboratory. Cost information came from the 2005 Drug Topics Red Book. 9 A Wilcoxon signed rank test was used to compare uric acid concentrations before and after administration of the rasburicase dose. Case Reports 807 Patient No. 1 A 64-year-old woman diagnosed with B-cell non-hodgkin s lymphoma from a mandibular lesion came to the hospital 12 days after surgery with increasing abdominal pain, weakness, and fatigue. Pertinent laboratory test results indicated that her white blood cell count was 10.4 x 10 3 /mm 3 (normal range x 10 3 /mm 3 ), platelet count 600 x 10 3 /mm 3 ( x 10 3 /mm 3 ), serum creatinine concentration 1.8 mg/dl ( mg/dl), calcium level 14.5 mg/dl ( mg/dl), and blood urea nitrogen (BUN) level 45 mg/dl (8 20 mg/dl). She was admitted to the hospital and immediately given intravenous hydration, intravenous pamidronate 60 mg, and allopurinol. On hospital day 2, her white blood cell count was 7.9 x 10 3 /mm 3, uric acid 11.7 mg/dl ( mg/dl), serum creatinine 1.7 mg/dl, calcium 12

3 808 PHARMACOTHERAPY Volume 26, Number 6, 2006 Table 1. Laboratory and Dosing Data for the 11 Patients Who Received a Single Dose of Rasburicase 6 mg Time from Dose Uric Acid Level Administration Rasburicase Before After to Decreased Serum Creatinine Actual Dose Relative to Patient Rasburicase Rasburicase Uric Acid Level Level Before Dose Weight Actual Weight No. (mg/dl) (mg/dl) (hrs) (mg/dl) (kg) (mg/kg) a b Median c a Patient no. 6 was readmitted for relapse of his acute lymphoblastic leukemia and received another 6-mg dose of rasburicase. b Patient no. 11 received a second, double dose (12 mg) of rasburicase the next day because his uric acid level decreased only slightly after the first (6-mg) dose. c p= mg/dl, and lactate dehydrogenase (LDH) 908 IU/L ( IU/L). Because of the patient s high tumor burden and worsening renal function compared with her preoperative baseline serum creatinine level (1.1 mg/dl), she was given a single dose of rasburicase 6 mg. The next morning, her uric acid level had declined to 4 mg/dl and remained below the upper limit of normal for the rest of her hospital stay (Table 1). Within 5 days of administration of the rasburicase dose, the patient s serum creatinine level returned to baseline and BUN to 20 mg/dl. She subsequently received treatment for management of her lymphoma. Patient No. 2 A 45-year-old woman with a history of renal cell carcinoma with subsequent nephrectomy, depression, and hypertension was diagnosed with relapsed non-hodgkin s lymphoma after coming to the clinic for her second cycle of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Clinic work-up revealed progressive lymphadenopathy, lymphocytosis, and LDH level of 1640 IU/L. At that time the patient was given additional rituximab and was admitted to the hospital for administration of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyper-cvad). Due to her significant tumor burden, she also received aggressive hydration with urinary alkalinization and a single dose of rasburicase 6 mg for TLS prophylaxis. Before she received the rasburicase dose, the patient s uric acid level was 8.2 mg/dl; this decreased to 3.9 mg/dl after approximately 3 hours. Her uric acid concentration continued to decline over the next 16 hours (Table 1). Uric acid and serum creatinine levels remained below the upper limit of normal during her chemotherapy treatment course. Patient No. 3 A 49-year-old woman with newly diagnosed B- cell non-hodgkin s lymphoma developed spontaneous tumor lysis with subsequent acute renal failure before the start of her chemotherapy. The patient s white blood cell count was 19.3 x 10 3 /mm 3, uric acid level 11.7 mg/dl, LDH level 580 IU/L, and serum creatinine concentration 3 mg/dl. She was given aggressive hydration with urinary alkalinization, allopurinol, and a single dose of rasburicase 6 mg. Allopurinol was discontinued after she developed a rash. After the rasburicase dose was administered, the patient s uric acid level decreased from 11.7 mg/dl to 2.1 mg/dl and remained below the upper limit of normal for the next 7 days (Table 1). On day 7 after administration of the rasburicase dose, CHOP was administered. However, the patient subsequently developed renal failure and

4 SINGLE-DOSE RASBURICASE IN ADULTS McDonnell et al required dialysis 3 times/week. She was given additional doses of rasburicase for prophylaxis during her hospital stay and required dialysis for approximately 15 days of her hospital stay. At discharge, however, she no longer required dialysis. Patient No. 4 A 56-year-old man went to a local hospital with complaints of increasing weakness, and inability to ambulate or eat. On arrival at our facility, his laboratory test results indicated a white blood cell count of 204 x 10 3 /mm 3, uric acid level 11.8 mg/dl, LDH level 503 IU/L, and serum creatinine concentration 2.4 mg/dl. He received hydration with urinary alkalinization, allopurinol, hydroxyurea, leukapheresis, and a single dose of rasburicase 6 mg. His uric acid level decreased to 2.9 mg/dl (Table 1). Work-up results led to a diagnosis of acute myeloid leukemia M4, and the patient received induction with cytarabine plus daunorubicin. Without additional rasburicase, his serum creatinine concentration decreased to 1.3 mg/dl within 5 days and returned to baseline within 10 days. Patient No. 5 A 62-year-old man with a history significant for hypertension, diabetes mellitus, gout, and chronic renal failure was transferred to our facility for management of a newly discovered posterior fossa cerebellar lesion. His baseline serum creatinine level was 2 mg/dl. The patient subsequently was diagnosed with chronic myelomonocytic leukemia. On admission, his laboratory test results revealed a white blood cell count of 185 x 10 3 /mm 3 with 5% blast cells, uric acid level 14.9 mg/dl, calcium level 8.3 mg/dl, LDH level 1884 IU/L, serum creatinine level 2.5 mg/dl, and BUN level 49 mg/dl. The patient received hydration with urinary alkalinization, leukapheresis, dexamethasone, and hydroxyurea. Within 24 hours of admission, he was given a single dose of rasburicase 6 mg; 5.5 hours after administration of the dose, his uric acid level decreased from 14.7 to 7.4 mg/dl and continued to decline to 5.1 mg/dl (Table 1). His uric acid level remained in the normal range for the rest of his hospital stay. Serum creatinine concentration remained elevated, peaking at 3.1 mg/dl, but declined to 2.1 mg/dl by discharge, consistent with the patient s baseline chronic renal failure. His BUN level continued to rise during his 10-day hospital stay and was 72 mg/dl 809 at discharge. The patient was discharged to home with instructions to follow up as an outpatient for future management of his head lesion and leukemia. Patient No. 6 A 22-year-old man with a history of Philadelphia chromosome-positive, acute lymphoblastic leukemia came to the hospital with increasing nausea, decreased appetite, and left upper quadrant pain over the previous week. Laboratory test results revealed a white blood cell count of 63.8 x 10 3 /mm 3 with 66% blast cells, platelet count 34 x 10 3 /mm 3, serum creatinine concentration 1.1 mg/dl, LDH level 887 IU/L, and uric acid level 7.5 mg/dl. He was admitted to the hospital. Because of his high risk for tumor lysis, he was given aggressive hydration with urinary alkalinization, allopurinol, and a single dose of rasburicase 6 mg before the start of chemotherapy with hyper-cvad and imatinib. The patient s uric acid level decreased to 0.5 mg/dl after the rasburicase dose (Table 1). He tolerated chemotherapy well, and his creatinine and uric acid levels remained stable for the rest of his hospital stay. This patient was readmitted for a second relapse of his acute lymphoblastic leukemia 2 months later and was treated with high-dose cytarabine and mitoxantrone. Significant laboratory findings on admission were a white blood cell count of 195 x 10 3 /mm 3 with 15% blast cells, platelet count 34 x 10 3 /mm 3, serum creatinine concentration 1.4 mg/dl, LDH level 1234 IU/L, uric acid level 11.8 mg/dl, and an undetectable phosphorus level. He received hydration with urinary alkalinization, allopurinol, and a single dose of rasburicase 6 mg. His uric acid concentration was 5.7 mg/dl 3 hours after administration of the rasburicase dose and continued to decline. It increased slightly but did not exceed the upper limit of normal during the patient s chemotherapy course. His serum creatinine concentration also continued to decline and remained within the normal range during the rest of his hospital stay. Patient No. 7 A 69-year-old man with a history of myelodysplastic syndrome, coronary artery disease, chronic renal insufficiency, and abdominal aortic aneurysm came to the clinic with a 20-lb weight loss over the preceding 2 3 months and increasing dyspnea while climbing stairs.

5 810 Laboratory test results revealed a white blood cell count of 229 x 10 3 /mm 3 with 50% blast cells. He was admitted to the hospital; laboratory test results indicated a white blood cell count of 265 x 10 3 /mm 3, serum creatinine concentration 2.7 mg/dl, LDH level 1233 IU/L, and uric acid level 16.8 mg/dl. The patient received leukapheresis, hydration with urinary alkalinization, allopurinol, hydroxyurea, and a single dose of rasburicase 6 mg. His uric acid concentration was 7.1 mg/dl 4 hours later and continued to decline (Table 1). Due to the patient s declining mental status and organ failure, the family declined further medical treatment, and he was discharged to a long-term care facility. Patient No. 8 A 63-year-old woman came to our facility with increased bruising and petechiae, rectal bleeding, and a white blood cell count of 46 x 10 3 /mm 3 noted on routine physical examination. Her history was significant for osteoporosis, hemorrhoids, and uterine cancer treated with radiation therapy and hysterectomy. She was admitted for further management and was diagnosed with acute myeloid leukemia. Significant laboratory findings on admission were a white blood cell count of 54.1 x 10 3 /mm 3 with 95% blast cells, platelet count 9 x 10 3 /mm 3, serum creatinine concentration 1.0 mg/dl, LDH level 1359 IU/L, and uric acid level 4.1 mg/dl. Tumor lysis prophylaxis was started with allopurinol and hydration with urinary alkalinization. Allopurinol was discontinued after the patient developed a fever thought to be a reaction to the allopurinol. Induction chemotherapy was started with cytarabine and daunorubicin. The patient received a single dose of rasburicase 6 mg on day 3 of chemotherapy, after her uric acid level increased to 7.4 mg/dl. Uric acid concentration promptly decreased to 0.8 mg/dl and remained in the low normal range for the rest of her chemotherapy course (Table 1). Patient No. 9 A 35-year-old man with a history of chronic myeloid leukemia in blast crisis was admitted to our facility for possible leukapheresis. He had first gone to a local hospital with increasing pain; laboratory test results revealed a white blood cell count of 96 x 10 3 /mm 3. Pertinent laboratory test results on admission to our facility indicated a white blood cell count of 100 x 10 3 /mm 3 with 7% blast cells, serum creatinine concentration 1.5 PHARMACOTHERAPY Volume 26, Number 6, 2006 mg/dl, LDH level 2069 IU/L, and uric acid level 10.1 mg/dl. Treatment was begun with hydroxyurea, hydration with alkalization, and allopurinol. The next day, the patient received a single dose of rasburicase 6 mg and induction chemotherapy with cytarabine and daunorubicin. His uric acid level, which was 7.3 mg/dl before the rasburicase dose, decreased to 1.1 mg/dl the next day and remained below the upper limit of normal throughout the rest of his hospital stay (Table 1). Patient No. 10 A 60-year-old man came to our facility with a history of liver transplantation due to hepatitis C. He was diagnosed as positive for human immunodeficiency virus and had renal failure; he subsequently was diagnosed with Burkitt s lymphoma. The patient initially received hydration with urinary alkalinization, allopurinol, and a single dose of rasburicase 6 mg. On the day of rasburicase administration, pertinent laboratory findings indicated a white blood cell count of 4.03 x 10 3 /mm 3, serum creatinine concentration 6.4 mg/dl, LDH level 401 IU/L, and uric acid level 10.3 mg/dl. His uric acid level decreased to 3.4 mg/dl 3.5 hours after the rasburicase dose was administered and continued to decline (Table 1). The patient subsequently received rituximab, corticosteroids, and intrathecal methotrexate. Before the start of therapy with hyper-cvad, the patient developed a renal vein thrombosis, hypotension, and respiratory distress; he died despite resuscitative measures. Patient No. 11 A 41-year-old, morbidly obese man (weight 259 kg, height 68 in., body mass index 87 kg/m 2 ) with a history of hypertension, diabetes mellitus, and heart failure was transferred to our facility after first going to another facility with weakness, anemia, hematuria, and rectal bleeding. On admission, laboratory test results indicated a white blood cell count of 104 x 10 3 /mm 3 with 90% blast cells, platelet count 43 x 10 3 /mm 3, serum creatinine concentration 3.2 mg/dl, uric acid level 17.4 mg/dl, and LDH level 1109 IU/L. The patient was treated with hydration, allopurinol, and a single dose of rasburicase 6 mg. The next day, the patient s uric acid level remained at 15.4 mg/dl, and the decision was made to administer a second, double dose (12 mg) of rasburicase. The day after administration

6 SINGLE-DOSE RASBURICASE IN ADULTS McDonnell et al of this dose, the patient s uric acid level decreased to 1.4 mg/dl (Table 1). Subsequently, he received prophylactic rasburicase 12 mg with his induction chemotherapy. Discussion In 10 of the 11 cases presented, the combination of allopurinol, intravenous hydration with urinary alkalinization, and a single dose of rasburicase 6 mg was effective in lowering uric acid concentration. In addition, renal function returned to baseline status in seven of the eight patients with renal dysfunction secondary to tumor lysis. Patient no. 10, whose renal function did not recover, died secondary to sepsis in the intensive care unit. In a retrospective case series, adult patients who had cancer with hyperuricemia received a single dose of rasburicase mg along with allopurinol and hydration. 10 The largest group, 12 patients, received a single dose of rasburicase 3 mg that resulted in a median decrease of 46% (range 31 68%) in uric acid concentration. No patient experienced clinically significant renal dysfunction. Only two patients in that case series received a single dose of rasburicase 6 mg. In our case series, which involved a single 6-mg dose, we observed a median decrease of 83% (range %) in uric acid concentration. This median decrease from 11.7 to 2.0 mg/dl was statistically significant (p=0.022; Table 1). Although a direct comparison of these two small case series is biased, the results suggest a doseresponse relationship with rasburicase. Patient no. 11 was a morbidly obese patient who did not respond to the initial single 6-mg dose of rasburicase. Data are limited regarding rasburicase dosing for morbidly obese adults. One case report described administration of a single dose of rasburicase 11 mg (0.2 mg/kg based on ideal body weight) in a 136-kg patient with chronic myeloid leukemia in blast crisis, likely experiencing tumor lysis. 11 Before the rasburicase dose was given, the patient s uric acid level was 11.9 mg/dl; this decreased to 5.1 mg/dl at 4 hours and 1.9 mg/dl at 48 hours after the dose. Another case report describing a morbidly obese patient also used rasburicase 0.2 mg/kg based on ideal body weight a single dose of rasburicase 12 mg. 10 The patient s serum uric acid concentration decreased from 11 mg/dl at baseline to 0.4 mg/dl 12 hours after the dose was given, and remained low. In contrast, when our morbidly obese patient (patient no. 11) was given the fixed dose of rasburicase 6 mg ( mg/kg based on actual body weight, 0.09 mg/kg based on ideal body weight), the response was not optimal; his uric acid level decreased from 17.4 to 15.4 mg/dl 7 hours after the dose was given (Table 1). However, after the second, 12- mg dose ( mg/kg based on actual, 0.18 mg/kg based on ideal body weight), his uric acid rapidly declined from 15.4 to 1.4 mg/dl. This limited information indicates that a single dose of rasburicase, dosed at mg/kg based on ideal body weight, may be effective for morbidly obese patients. Rasburicase is available only in single-use 1.5- mg vials; therefore, rounding doses to 1.5-mg increments is prudent. Another limitation is its cost; the average wholesale price for a package of three 1.5-mg vials of rasburicase is $ , or $386.78/1.5-mg vial. 9 Extrapolating the approved pediatric dose of 0.15 mg/kg to the dose for a 75- kg adult results in one dose of rasburicase mg/day for 5 days. This amounts to an average wholesale price of $ /day, and $14, for 5 days. A single dose of rasburicase 6 mg would cost $ , for an overall savings of $12,957.13/patient. Conclusion Tumor cell lysis can be a potentially lifethreatening complication that requires quick and aggressive management to prevent acute renal failure. Findings from these case reports warrant further investigation of using a single 6-mg dose of rasburicase, along with allopurinol, intravenous hydration, and urinary alkalinization in adults with TLS or adults who have a high risk of developing TLS. A fixed dose of rasburicase 6 mg for nonobese patients and mg/kg for morbidly obese patients (based on ideal body weight and rounded to the contents of a vial) may be a reasonable, efficient, and cost-effective option in the management of adults with hyperuricemia secondary to tumor lysis or those at risk of TLS. References Bishop MR, Cairo MS, Coccia PF. Tumor lysis syndrome. In: Abeloff MD, Armitage JO, Niederhuber JE, Kastan MB, McKenna WG, eds. Clinical oncology. Orlando, FL: Churchill Livingstone, 2004: Davidson MB, Thakkar S, Hix JK, Bhandarkar ND, Wong A, Schreiber MJ. Pathophysiology, clinical consequences, and treatment of tumor lysis syndrome. Am J Med 2004;116:

7 812 PHARMACOTHERAPY Volume 26, Number 6, Pui CH, Mahmoud HH, Wiley JM, et al. Recombinant urate oxidase for the prophylaxis or treatment of hyperuricemia in patients with leukemia or lymphoma. J Clin Oncol 2001;19: Sanofi-Synthelabo. Elitek (rasburicase) package insert. New York, NY; Coiffler B, Mounier N, Bologna S, et al. Efficacy and safety of rasburicase (recombinant urate oxidase) for the prevention and treatment of hyperuricemia during induction chemotherapy of aggressive non-hodgkin s lymphoma: results of the GRAAL1 (groupe d etude des lymphomes de l adulte trial on rasburicase activity in adult lymphoma) study. J Clin Oncol 2003;21: Lee AC, Li CH, So KT, Chan R. Treatment of impending tumor lysis with single-dose rasburicase. Ann Pharmacother 2003;37: Hummel M, Buchheidt D, Reiter S, Bergmann J, Hofheinz R, Hehlmann R. Successful treatment of hyperuricemia with low doses of recombinant urate oxidase in four patients with hematologic malignancy and tumor lysis syndrome. Leukemia 2003;17: Liu CY, Sims-McCallum RP, Schiffer CA. A single dose of rasburicase in patients receiving chemotherapy. Leuk Res 2005:29: Fleming T, ed. Drug topics red book. Montvale, NJ: Thomson PDR, 2005: Trifilio S, Tallman M, Singhal S, Gordon L, Evens A, Mehta J. Low-dose recombinant urate oxidase (rasburicase) is effective in hyperuricemia [abstr]. Blood 2004;104(suppl 1):905a. 11. Arnold TM, Reuter JP, Delman BS, Shanholtz CB. Use of single-dose rasburicase in an obese female. Ann Pharmacother 2004;38: