Department of Pharmacy, Arthur G. James Cancer Hospital, The Ohio State University, Columbus, OH 43210, USA.
Pharmacotherapy. 2013 Mar;33(3):295-303. doi: 10.1002/phar.1198.
To evaluate single fixed dosing versus weight-based dosing strategies for rasburicase to determine the minimum dose required to mitigate hyperuricemia in the treatment or prevention of tumor lysis syndrome.
Retrospective medical record review
Academic medical center
A total of 373 patients with a diagnosis of a hematologic malignancy or solid tumor and who received at least one dose of rasburicase over a 6-year period between January 1, 2005, and February 18, 2011; 180 patients received single doses of 3 mg (38 patients), 6 mg (99 patients), or 7.5 mg (43 patients), and 193 patients received weight-based dosing.
Tumor lysis syndrome laboratory data were recorded at baseline and monitored up to 72 hours after initial rasburicase administration. Median baseline plasma uric acid levels were 6.85 mg/dl, 8.80 mg/dl, 8.00 mg/dl, and 9.20 mg/dl, respectively, in the 3-mg, 6-mg, 7.5-mg, and weight-based dosing groups. Treatment success was defined as a normalized plasma uric acid level (< 7.5 mg/dl) within 24 hours after receiving rasburicase. The mean weight-based dose was 0.16 mg/kg. Six rasburicase treatment failures occurred; two were in the 3-mg group, one was in the 6-mg group, and three were in the weight-based dosing group. At 24 hours after rasburicase administration, no statistically significant differences in treatment success were noted among groups (92.9% vs 97.6% vs 100.0% vs 98.0% in the 3-mg, 6-mg, 7.5-mg, and weight-based dosing groups, respectively, p=0.1238).
The efficacy of all single fixed doses and weight-based dosing strategies evaluated in this study appear to be comparable in normalizing plasma uric acid levels within 24 hours of rasburicase administration. Although use of a 3-mg rasburicase dose may be the most cost-effective treatment strategy in managing hyperuricemia secondary to tumor lysis syndrome, the 6-mg dose resulted in lower sustained uric acid levels after rasburicase administration. Further analysis of patient specific factors contributing to the need for repeat rasburicase administration should be conducted in larger, prospective clinical trials.
评估拉布立酶的单剂量固定方案与基于体重的方案，以确定在治疗或预防肿瘤细胞溶解综合征时降低血尿酸水平所需的最小剂量。
回顾性病历审查
学术医疗中心
共 373 例患有血液恶性肿瘤或实体瘤的患者，在 2005 年 1 月 1 日至 2011 年 2 月 18 日的 6 年期间内至少接受了一次拉布立酶治疗；180 例患者接受了单剂量 3mg（38 例）、6mg（99 例）或 7.5mg（43 例），193 例患者接受了基于体重的方案。
在初始拉布立酶给药后 72 小时内监测肿瘤细胞溶解综合征的实验室数据。3mg、6mg、7.5mg 和基于体重的方案组的基线血浆尿酸水平中位数分别为 6.85mg/dl、8.80mg/dl、8.00mg/dl 和 9.20mg/dl。治疗成功定义为接受拉布立酶后 24 小时内血浆尿酸水平正常化（<7.5mg/dl）。基于体重的平均剂量为 0.16mg/kg。6 例拉布立酶治疗失败，其中 2 例在 3mg 组，1 例在 6mg 组，3 例在基于体重的方案组。拉布立酶给药后 24 小时，各组间治疗成功率无统计学差异（3mg、6mg、7.5mg 和基于体重的方案组分别为 92.9%、97.6%、100.0%和 98.0%，p=0.1238）。
本研究中评估的所有单剂量固定方案和基于体重的方案在拉布立酶给药后 24 小时内使血浆尿酸水平正常化的疗效似乎相当。尽管使用 3mg 拉布立酶剂量可能是管理肿瘤细胞溶解综合征引起的高尿酸血症的最具成本效益的治疗策略，但 6mg 剂量在拉布立酶给药后导致尿酸水平持续较低。应在更大的前瞻性临床试验中进一步分析导致需要重复拉布立酶给药的患者特定因素。
