NEW YORK -- October 19, 2009 -- The US Food and Drug Administration (FDA) has approved rasburicase (Elitek) to be used for the initial management of plasma uric acid (PUA) levels in adult patients with leukaemia, lymphoma, and solid tumour malignancies who are receiving anti-cancer therapy expected to result in tumour lysis syndrome (TLS) and subsequent elevations of plasma uric acid.
The approval was based on a phase 3 trial in adults with haematologic cancers at risk for the potentially life-threatening complication of TLS. Patients considered at high risk for TLS either had hyperuricemia due to a malignancy, or were diagnosed with a very aggressive haematologic malignancy.
The primary objective of the multicentre, open-label, randomised, parallel group comparative study was to compare the safety and the effectiveness of intravenous rasburicase alone daily for 5 days, intravenous rasburicase daily for day 1 to day 3 followed by oral allopurinol daily for day 3 to day 5, and oral allopurinol alone daily for 5 days in achieving uric acid response rate.
The daily dose of rasburicase was 0.20 mg/kg, while that of allopurinol was 300 mg. The PUA response rate was defined as the proportion of patients with PUA levels <= 7.5 mg/dL from day 3 to day 7 after initiation of treatment.
Results showed that among patients treated with rasburicase alone or followed by oral allopurinol, uric acid levels were <= to 2.0 mg/dL in 96% of patients (at 4 hours of the day 1 dose). There were no patients in either rasburicase group with documented failure to control uric acid.
In patients treated with rasburicase alone (n = 92), the PUA response rate was 87%, which was higher than that seen with patients treated with oral allopurinol alone (n = 91) at 66% (P = .0009), a statistically significant difference, or those treated with the rasburicase/oral allopurinol combination (n = 92) at 78%. The rasburicase versus rasburicase/oral allopurinol combination difference in PUA response rate was not statistically significant.
Antihyperuricemic treatment was extended beyond 5 days in 4.4% of patients treated with oral allopurinol alone and 6.5% of patients treated with the rasburicase /oral allopurinol combination, versus 0% of patients receiving rasburicase alone. Clinical TLS occurred in 3% of rasburicase -treated patients, 3% of rasburicase/oral allopurinol-treated patients, and 4% of oral allopurinol-treated patients.
Hypersensitivity reactions occurred in 4.3% of patients treated with rasburicase alone and 1.1% of patients treated with the rasburicase/oral allopurinol combination.
Hypersensitivity reactions included arthralgia, injection site irritation, peripheral oedema, and rash. The most common grade 3/4 related adverse reactions regardless of relationship to study drug were sepsis (5.4%/6.5%/4.4%), hypophosphatemia (4.3%/6.5%/6.6%), anxiety (3.3%/0%/0%), abdominal pain (3.3%/4.3%/2.2%), hyperbilirubinemia (3.3%/2.2%/4.4%), and increased alanine aminotransferase (3.3%/4.3%/2.2%) in the rasburicase, rasburicase/oral allopurinol, and oral allopurinol arms, respectively.
All patients were receiving anti-cancer chemotherapy and/or biologic anti-cancer agents for their primary disease.
The following serious adverse reactions occurred with a difference in incidence of >= 2% in patients receiving rasburicase compared with patients receiving oral allopurinol: pulmonary haemorrhage, respiratory failure, supraventricular arrhythmias, ischaemic coronary artery disorders, and abdominal and gastrointestinal infections.
SOURCE: Sanofi-Aventis
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