A randomized trial of a single-dose rasburicase versus five-daily doses in patients at risk for tumor lysis syndrome.
BACKGROUND
Tumor lysis syndrome (TLS) is a life-threatening disorder characterized by hyperuricemia and metabolic derangements. The efficacy of rasburicase, administered daily for 5 days, has been well established. However, the optimal duration of therapy is unknown in adults.


METHODS
We evaluated the efficacy of rasburicase (0.15 mg/kg) administered as single dose followed by as needed dosing (maximum five doses) versus daily dosing for 5 days in adult patients at risk for TLS.


RESULTS
Eighty of the 82 patients enrolled received rasburicase; 40 high risk [median uric acid (UA) 8.5 mg/dl; range, 1.5-19.7] and 40 potential risk (UA = 5.6 mg/dl; range, 2.4-7.4). Seventy-nine patients (99%) experienced normalization in their UA within 4 h after the first dose; 84% to an undetectable level (<0.7 mg/dl). Thirty-nine of 40 (98%) patients in the daily-dose arm and 34 of 40 (85%) patients in single-dose arm showed sustained UA response. Six high-risk patients within the single-dose arm required second dose for UA >7.5 mg/dl. Rasburicase was well tolerated; one patient with glucose-6-phosphate dehydrogenase deficiency developed methemoglobinemia and hemolysis.


CONCLUSIONS
Rasburicase is highly effective for prevention and management of hyperuricemia in adults at risk for TLS. Single-dose rasburicase was effective in most patients; only a subset of high-risk patients required a second dose.
Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, MD, USA. svadhanr@mdanderson.org
S
S
Vadhan-Raj
L E
LE
Fayad
M A
MA
Fanale
B
B
Pro
A
A
Rodriguez
F B
FB
Hagemeister
C E
CE
Bueso-Ramos
X
X
Zhou
P W
PW
McLaughlin
N
N
Fowler
J
J
Shah
R Z
RZ
Orlowski
F
F
Samaniego
M
M
Wang
J E
JE
Cortes
A
A
Younes
L W
LW
Kwak
N J
NJ
Sarlis
J E
JE
Romaguera
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D006074:Gout Suppressants / Q000008:administration & dosage* / Q000627:therapeutic use; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D016896:Treatment Outcome; D015275:Tumor Lysis Syndrome / Q000209:etiology / Q000517:prevention & control*; D014503:Urate Oxidase / Q000008:administration & dosage* / Q000627:therapeutic use; D014527:Uric Acid / Q000097:blood
D000970:Antineoplastic Agents; D006074:Gout Suppressants; C469709:rasburicase; D014527:Uric Acid; D014503:Urate Oxidase