Sanofi-aventis has announced results of a randomized phase III study presented at the 50th Annual Meeting of the American Society of Hematology.
The study in adult patients with hematological malignancies at high or potential risk for tumor lysis syndrome (TLS) demonstrated that Elitek(R) (rasburicase) significantly reduced plasma uric acid (PUA) levels compared to allopurinol alone (p=0.0012). The study also compared a sequential combination of the two agents (Elitek for three days followed by allopurinol for three days, with one day overlap) versus allopurinol alone, which showed a reduction in plasma uric acid levels for the sequential combination versus allopurinol alone (p=0.06).
Tumor lysis syndrome is a potentially life-threatening metabolic complication that can result either spontaneously or following treatment of certain types of rapid-growing cancers, particularly leukemia or lymphoma. The syndrome develops when a particularly large volume of cells associated with fast growing tumors are destroyed, releasing cellular by-products into the blood system such as uric acid, faster than can be eliminated. Elevated levels of plasma uric acid can cause hyperuricemia, a serious condition that can lead to renal failure if not controlled.
The primary objective of the multi-center, open-label, randomized, parallel group comparative study was to compare the adequacy of control of PUA concentration and the safety profile in three treatment arms. Among the three treatment arms, plasma uric acid response rate (defined as normalization or maintenance of PUA levels less than or equal to 7.5mg/dl at days 3-7) was 87% of patients treated with Elitek compared to 66% receiving allopurinol alone (p=0.001) and 78% with Elitek/allopurinol (p=0.06). Among patients at high risk for tumor lysis syndrome, the PUA response rate was 89% with Elitek vs. 68% with allopurinol and 79% with the Elitek/allopurinol combination (p=0.0012). The PUA response rate among patients with baseline hyperuricemia defined as plasma uric acid >7.5mg/dL was 90% with Elitek versus 53% with allopurinol and 77% with Elitek/allopurinol (p=0.0151). The time to control, or normalize, PUA in hyperuricemic patients was 4.1 hours among patients treated with Elitek (n=18 [95% CI=4.0 to 4.5]), 4.1 hours with the Elitek/allopurinol combination (n=12 [95% CI=3.9 to 4.5) and 27.0 hours in the allopurinol alone arm (n=17 [95% CI=4.0 to 49.0]).
"In this investigational study, Elitek controlled plasma uric acid in a larger percentage of patients and in a shorter period of time than allopurinol, the current U.S. standard treatment in adults," said principal investigator Dr. Jorge Cortes, Professor of Medicine and Deputy Chair, Department of Leukemia at The University of Texas, MD Anderson Cancer Center, in Houston, Texas.