Abstract
Tumor lysis syndrome (TLS), including hyperuricemia, is a frequent serious complication in patients with hematologic malignancies. This study in Japanese patients evaluated the efficacy, safety, and pharmacokinetic profile of rasburicase in pediatric patients with hematologic malignancies. Patients aged <18 years at high risk for TLS, with newly diagnosed hematologic malignancies, were randomized to intravenous rasburicase 0.15 mg/kg/day (n = 15) or 0.20 mg/kg/day (n = 15) for 5 days. Chemotherapy was started 4–24 h after the first rasburicase dose. Response was defined as a reduction in plasma uric acid to ≤6.5 mg/dL (patients <13 years) or ≤7.5 mg/dL (patients ≥13 years) by 48 h after the first administration, lasting until 24 h after the final administration. Response rates were 93.3 and 100% with rasburicase 0.15 and 0.20 mg/kg/day, respectively. Uric acid levels declined rapidly within 4 h of starting rasburicase administration in both groups. Most adverse events were related to the underlying chemotherapy regimens. Two hypersensitivity reactions, including grade 1/2 pruritus, were considered to be related to rasburicase. Rasburicase is effective and well tolerated for the management of hyperuricemia in Japanese pediatric patients at high risk of developing TLS.
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Acknowledgments
We thank the following additional investigators: Shoichi Koizumi, M.D., Ph.D. (Department of Pediatrics, Kanazawa University Hospital); Akira Ohara, M.D. (Department of Blood Transfusion, Toho University Omori Medical Center); Yoshihiro Komada, M.D., Ph.D. (Institute of Molecular and Experimental Medicine, Mie University Hospital); Takashi Kaneko, M.D. (Department of Hematology/Oncology, Tokyo Metropolitan Kiyose Children’s Hospital). Members of the Efficacy and Safety Evaluation Committee: Fumio Bessho, M.D. (Kyorin University Hospital); Shuki Mizutani, M.D. (Tokyo Medical and Dental University Hospital); Hideo Mugishima, M.D. (Nihon University Itabashi Hospital). Other participating institutions: Nippon Medical School Hospital; National Center for Child Health and Development; Tohoku University Hospital, Saga Medical School Hospital; Shizuoka Children’s Hospital; National Hospital Organization Hokkaido Cancer Center; Hiroshima University Hospital. Editorial support provided by sanofi-aventis.
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Kikuchi, A., Kigasawa, H., Tsurusawa, M. et al. A study of rasburicase for the management of hyperuricemia in pediatric patients with newly diagnosed hematologic malignancies at high risk for tumor lysis syndrome. Int J Hematol 90, 492–500 (2009). https://doi.org/10.1007/s12185-009-0402-6
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DOI: https://doi.org/10.1007/s12185-009-0402-6