Nauffal Mary, Redd Robert, Ni Jian, Stone Richard M, DeAngelo Daniel J, McDonnell Anne M
1 Department of Pharmacy Services, Brigham and Women's Hospital, Boston, MA, USA.
2 Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA, USA.
J Oncol Pharm Pract. 2019 Sep;25(6):1349-1356. doi: 10.1177/1078155218791333. Epub 2018 Aug 15.
Tumor lysis syndrome is an oncologic emergency due to the release of tumor cell contents, leading to metabolic derangements. Rasburicase, a recombinant urate oxidase, catabolizes uric acid. At our institution, we administer a single 6-mg dose of rasburicase to patients who are at risk for tumor lysis syndrome. We aimed to assess the efficacy of single 6-mg dose of rasburicase and explore risk factors associated with rasburicase failure.
We report results in 92 adult patients who had a baseline uric acid greater than 7.5 mg/dL and received a single 6-mg dose of rasburicase for the management of tumor lysis syndrome. Responders were defined as those whose uric acid was less than or equal to 7.5 mg/dL within 24-36 h of rasburicase administration. The primary end point was response based on uric acid level. Secondary end points included response to rasburicase in association with lactate dehydrogenase, serum creatinine, calcium, phosphorus, blood pH, and oncologic diagnosis.
Median age was 65 years and 70% were men. Most patients had leukemia (32%) or lymphoma (40%). Eighty-seven of 92 patients (95%), who received single 6-mg dose of rasburicase, achieved a uric acid less than 7.5 mg/dL within 24-36h of dosing. Body mass index was similar between responders and non-responders: 28.6 kg/m vs. 26.6 kg/m, respectively, p = 0.6. Baseline lactate dehydrogenase levels were similar between the groups: 756 U/L vs. 892 U/L, respectively, p = 0.33. Blood pH values documented within 24 h of first dose of rasburicase were also similar between the two groups (n = 30; 7.33 vs. 7.34 respectively, p = 0.6). However, median baseline uric acid was lower in responders than non-responders: 12.3 mg/dL vs. 17.3 mg/dL, respectively, p = 0.012. Baseline serum creatinine and creatinine clearance were similar between responders and non-responders (2.2 mg/dL vs. 3.95 mg/dL; p = 0.12 and 29 mL/min vs. 16 mL/min; p = 0.11, respectively).
Higher baseline uric acid levels were observed in patients who did not respond to the first rasburicase dose. In our study, uric acid levels normalized in 95% of patients after a single 6-mg dose of rasburicase indicating that a single 6-mg dose of rasburicase may be sufficient to manage tumor lysis syndrome, for most patients.
肿瘤溶解综合征是一种肿瘤急症，由于肿瘤细胞内容物的释放，导致代谢紊乱。拉布立酶是一种重组尿酸氧化酶，可分解尿酸。在我们机构，我们给有肿瘤溶解综合征风险的患者单次静脉注射6毫克拉布立酶。我们旨在评估单次6毫克剂量拉布立酶的疗效，并探讨与拉布立酶治疗失败相关的危险因素。
我们报告了92例成年患者的结果，这些患者基线尿酸水平大于7.5mg/dL，并接受单次6毫克剂量的拉布立酶治疗肿瘤溶解综合征。反应者定义为在拉布立酶给药后24 - 36小时内尿酸水平小于或等于7.5mg/dL的患者。主要终点是基于尿酸水平的反应。次要终点包括拉布立酶治疗反应与乳酸脱氢酶、血清肌酐、钙、磷、血液pH值及肿瘤诊断的相关性。
中位年龄为65岁，70%为男性。大多数患者患有白血病（32%）或淋巴瘤（40%）。92例接受单次6毫克剂量拉布立酶治疗的患者中，87例（95%）在给药后24 - 36小时内尿酸水平降至7.5mg/dL以下。反应者与无反应者的体重指数相似：分别为28.6kg/m²和26.6kg/m²，p = 0.6。两组的基线乳酸脱氢酶水平相似：分别为756U/L和892U/L，p = 0.33。首次剂量拉布立酶后24小时内记录的血液pH值在两组中也相似（n = 30；分别为7.33和7.34，p = 0.6）。然而，反应者的基线尿酸中位数低于无反应者：分别为12.3mg/dL和17.3mg/dL，p = 0.012。反应者与无反应者的基线血清肌酐和肌酐清除率相似（分别为2.2mg/dL和3.95mg/dL；p = 0.12和29mL/min和16mL/min；p = 0.11）。
首次拉布立酶剂量治疗无反应的患者基线尿酸水平较高。在我们的研究中，单次6毫克剂量的拉布立酶使95%的患者尿酸水平恢复正常，这表明对于大多数患者，单次6毫克剂量的拉布立酶可能足以治疗肿瘤溶解综合征。
