On October 16, 2009, the U.S. Food and Drug Administration granted approval for the use of  (Elitek®, Sanofi-aventis, U.S.) for the initial management of plasma uric acid levels in adult patients with leukemia, lymphoma, and solid tumor malignancies who are receiving anticancer therapy expected to result in tumor lysis and subsequent elevation of plasma uric acid. The approval was based on results from the EFC 4978 trial which demonstrated a significant improvement in uric acid response rates (the proportion of patients with plasma uric acid levels =7.5 mg/dL from day 3 through day 7 following initiation of antihyperuricemic treatment) among rasburicase treated patients compared to allopurinol treated patients.

Clinical trial EFC 4978 was a randomized (1:1:1), multicenter, open-label trial conducted in patients with leukemia, lymphoma, and solid tumor malignancies at risk for hyperuricemia and tumor lysis syndrome (TLS). A total of 275 adult patients received at least one dose of trial drug. The median age was 56 years, 62% were males, 66% had leukemia, 29% had lymphoma, and 18% were hyperuricemic (uric acid >7.5mg/dL) at entry. Patients in Arm A received rasburicase for 5 days (n=92). Patients in Arm B received rasburicase from day 1 through day 3 followed by oral allopurinol from day 3 through day 5 (overlap on day 3: rasburicase and allopurinol administered approximately 12 hours apart) (n=92). Patients in Arm C received oral allopurinol for 5 days (n=91). Rasburicase was administered at the dose of 0.2 mg/kg/day as a 30-minute infusion once daily. Allopurinol was administered orally at the dose of 300 mg once a day. The main outcome measure of this trial was the uric acid response rate, as described above.

The uric acid response rate in Arm A and C was 87% versus 66%, respectively (p=0.0009). No significant difference in the uric acid response rates were noted between Arms B and C. There was no difference between the arms in the incidence of TLS.

Box and whisker plots of uric acid levels at various timepoints show a rapid reduction in uric acid level, with uric acid levels <2 mg/dL in 96% of rasburicase -treated patients at 4 hours following the first dose.

The adverse reactions related to rasburicase observed during the EFC 4978 trial were consistent in nature and severity to the labeled adverse reactions.

Serious adverse reactions occurring at a difference in incidence of =2% in patients receiving rasburicase compared to patients receiving allopurinol in randomized trials included pulmonary hemorrhage, respiratory failure, supraventricular arrhythmias, ischemic coronary artery disorders, and abdominal and gastrointestinal infections. The incidence of anaphylaxis, hemolysis, and methemoglobinemia occurred in <1% of the 887 rasburicase-treated patients in clinical trials.

The most common toxicities occurring at an overall incidence =10% with the largest difference between the rasburicase arm versus the allopurinol arm in the EFC 4978 trial included peripheral edema (50%), vomiting (38%), hyperbilirubinemia (16%), sepsis (12%), and fluid overload (12%). 

Full prescribing information, including clinical trial information, safety, dosing, drug-drug interactions and contraindications is available at the FDA website