European experience in the treatment of hyperuricemia

The nonrecombinant form of urate oxidase has been routinely used in France since 1975 as standard practice in the initial management of non-Hodgkin's lymphoma (NHL) and acute lymphoblastic leukemia (ALL), and for prevention of tumor lysis syndrome (TLS). A retrospective study was performed to evaluate the frequency of metabolic complications and dialysis in 410 patients with B-cell stage III and IV NHL and L-3 ALL treated in France according to the LMB89 protocol, and to compare these results to those of other series of patients treated without urate oxidase. Of the 57 patients treated at Institut Gustave-Roussy, only five had metabolic complications occurring in the first cycle of chemotherapy. Two patients (3.5%) underwent dialysis: one because of oliguria, the second for preventive reasons. In all the other cases, metabolic problems were successfully resolved or prevented, using nonrecombinant urate oxidase (Uricozyme, Sanofi-Sythélabo, Inc, Paris, France) in combination with hyperhydration. Nonrecombinant urate oxidase is generally well tolerated. However, allergic reactions may occur, with rates varying from 0% to 4.5%. In addition, the extraction technology used to produce the product is limited by a low yield. A recombinant form of urate oxidase (rasburicase) was therefore developed. European clinical development results indicate that this agent produces a sharp and consistent decrease in uric acid levels in patients undergoing cytoreductive therapy. Additionally, there is a very low incidence of anaphylaxis. Studies have demonstrated the efficacy of urate oxidase in lowering uric acid levels, preventing hyperuricemia after the initiation of cytoreductive therapy, and preserving renal function in patients with B-cell advanced stage NHL and ALL.