Source: DGNews  |  Posted 2 years ago

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