Recombinant urate oxidase for the prophylaxis or treatment of hyperuricemia in patients with leukemia or lymphoma
Recombinant urate oxidase for the prophylaxis or treatment of hyperuricemia in patients with leukemia or lymphoma
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DOI：
10.1200/jco.2001.19.3.697
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发表时间：
2001-02-01
影响因子：
45.3
通讯作者：
Reaman, GH
中科院分区：
文献类型：
--
作者：
Pui, CH;Mahmoud, HH;Reaman, GH
目的：为了改善白血病或淋巴瘤患者高尿酸血症的中枢神经系统，我们测试了一种新开发的尿酸溶解剂，重组尿酸氧化酶（SR 29142;拉布立海; Sanofi-Synthalio，Inc，巴黎，法国），其催化尿酸氧化为尿囊素，尿囊素是一种易于由肾脏排泄的高度水溶性代谢物。我们对131例新诊断白血病或淋巴瘤的儿童、青少年和年轻成人（他们的血浆尿酸浓度异常高或肿瘤细胞负荷大）连续5 - 7天静脉给予拉布立海0.15或0.20 mg/kg。每天测量血液中的尿酸、肌酸酐、磷和钾水平。拉布立海的药代动力学，尿排泄率的尿囊素，抗体拉布立海也studyed.Results：在任何剂量，重组酶产生了快速和急剧下降，在所有患者的血浆尿酸浓度。治疗后4小时，65例高尿酸血症患者的中位水平从9.7降至1 mg/dL（P = .0001），其余66例患者的中位水平从4.3降至0.5 mg/dL（P = .0001）。尽管进行了细胞减灭化疗，但整个治疗期间血浆尿酸浓度仍较低（每日中位数水平为0.5 mg/dL）。拉布立海治疗期间，尿中尿囊素排泄率增加，在第3天达到峰值。在治疗的前3天内，血清磷浓度没有显著变化，在高尿酸血症患者中，血清磷浓度在第4天显著下降（P = 0.0003），在治疗后48小时，所有患者的血清磷浓度均在正常范围内。在诊断时有或无高尿酸血症的患者中，治疗1天后血清肌酐水平显著降低（分别为P = 0.0003和P = 0.02），治疗第6天所有患者均恢复正常范围。毒性可以忽略不计，没有患者需要透析。在接受0.15或0.20 mg/kg剂量治疗的患者中，药物的平均血浆半衰期分别为16.0 +/- 6.3（SD）小时和21.1 +/- 12.0小时。121名可评估患者中有17名产生了该酶的抗体。结论：拉布立酶对于预防或治疗白血病或淋巴瘤患者的高尿酸血症是安全且高效的。(C)2001年，美国临床肿瘤学会。
Purpose: To improve the central of hyperuricemia in patients with leukemia or lymphoma, we tested a newly developed uricolytic agent, recombinant urate oxidase (SR29142; Rasburicase; Sanofi-Synthelabo, Inc, Paris, France), which catalyses the oxidation of uric acid to allantoin, a highly water-soluble metabolite readily excreted by the kidneys.Patients and Methods: We administered Rasburicase intravenously, at 0.15 or 0.20 mg/kg, for 5 to 7 consecutive days to 131 children, adolescents, and young adults with newly diagnosed leukemia or lymphoma, who ei; ther presented with abnormally high plasma uric acid concentrations or had large tumor cell burdens. Blood levels of uric acid, creatinine, phosphorus, and potassium were measured daily. The pharmacokinetics of Rasburicase, the urinary excretion rate of allantoin, and antibodies to Rasburicase were also studied.Results: At either dosage, the recombinant enzyme produced a rapid and sharp decrease in plasma uric acid concentrations in all patients. The median level decreased by 4 hours after treatment, from 9.7 to 1 mg/dL (P = .0001), in the 65 patients who presented with hyperuricemia, and from 4.3 to 0.5 mg/dL (P = .0001) in the remaining 66 patients. Despite cytoreductive chemotherapy, plasma uric acid concentrations remained low throughout the treatment (daily median level, 0.5 mg/dL). The urinary excretion rate of allantoin increased during Rasburicase treatment, peaking on day 3. Serum phosphorus concentrations did not change significantly during the first 3 days of treatment, decreased significantly by day 4 in patients presenting with hyperuricemia (P = .0003), and fell within the normal range in all patients by 48 hours after treatment. Serum creatinine levels decreased significantly after 1 day of treatment in patients with or without hyperuricemia at diagnosis (P = .0003 and P = .02, respectively) and returned fa normal range in all patients by day 6 of treatment. Toxicity was negligible, and none of the patients required dialysis. The mean plasma half-lives of the agent were 16.0 +/- 6.3 (SD) hours and 21.1 +/- 12.0 hours, respectively, in patients treated at dosages of 0.15 or 0.20 mg/kg. Seventeen of the 121 assessable patients developed antibodies to the enzyme.Conclusion: Rasburicase is safe and highly effective for the prophylaxis or treatment of hyperuricemia in patients with leukemia or lymphoma. (C) 2001 by American Society of Clinical Oncology.