Department of Hematology and Oncology, Faculty of Medical Sciences, University of Fukui, Fukui, Japan.
Department of Hematology and Oncology, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
Anticancer Res. 2014 Dec;34(12):7287-96.
BACKGROUND/AIM: Tumor lysis syndrome (TLS) is a life-threatening oncological emergency, and control of serum uric acid level (S-UA) is most important. In this single-institution, short-term and pilot prospective study, the efficacy of a new xanthine oxidase inhibitor, febuxostat, as an alternative to conventional allopurinol, including its effects on hypoxanthine and xanthine, was evaluated in 10 consecutive patients with hematological malignancies at intermediate risk for TLS.
Febuxostat at 40 mg (n=7) or 60 mg (n=3) daily was administered according to renal function, and induction chemotherapy was started within 24 h. The primary end-point was the reduction of S-UA to ≤ 7.5 mg/dl by day 5.
The median S-UA at base-line was 8.0 mg/dl (range=3.2-10.6 mg/dl). The median S-UA on day 5 after chemotherapy was 3.3 mg/dl (range=1.1-5.8 mg/dl) (p<0.0001, by paired t-test), indicating successful control of S-UA during chemotherapy. All patients achieved S-UA ≤ 7.5 mg/dl. A simultaneous decrease in serum creatinine and increase in estimated glomerular filtration rate were seen. Serum hypoxanthine and xanthine levels (as the consequence of inhibition of xanthine oxidase) were elevated along with the decrease in S-UA. Xanthine level was elevated higher compared to hypoxanthine level and reached the level reported to cause xanthine nephropathy, but no advance of renal impairment was observed. Serum febuxostat concentrations at 2 h after administration were 891.8 ± 285.0 ng/ml (mean ± SE) for the 40-mg dose and 770.6 ± 242.7 ng/ml for the 60-mg dose (p=0.80, unpaired t-test), showing no accumulation in patients with renal impairment. No febuxostat-related adverse reactions were noted. No patients experienced progressive TLS.
Febuxostat is promising for the management of TLS of an intermediate-risk patient and further observation and reevaluation regarding xanthine nephropathy should be performed.
背景/目的：肿瘤溶解综合征（TLS）是一种危及生命的肿瘤急症，控制血清尿酸水平（S-UA）最为重要。在这项单中心、短期、前瞻性研究中，评估了新型黄嘌呤氧化酶抑制剂非布司他作为传统别嘌醇的替代品在 10 例血液恶性肿瘤中中度 TLS 风险患者中的疗效，包括其对次黄嘌呤和黄嘌呤的影响。
根据肾功能，每天给予非布司他 40mg（n=7）或 60mg（n=3），并在 24 小时内开始诱导化疗。主要终点是第 5 天 S-UA 降至≤7.5mg/dl。
基线时 S-UA 的中位数为 8.0mg/dl（范围 3.2-10.6mg/dl）。化疗后第 5 天 S-UA 的中位数为 3.3mg/dl（范围 1.1-5.8mg/dl）（p<0.0001，配对 t 检验），表明化疗期间 S-UA 得到成功控制。所有患者的 S-UA 均≤7.5mg/dl。同时观察到血清肌酐降低和估算肾小球滤过率升高。随着 S-UA 的降低，血清次黄嘌呤和黄嘌呤水平（由于黄嘌呤氧化酶的抑制）升高。黄嘌呤水平升高高于次黄嘌呤水平，达到引起黄嘌呤肾病的水平，但未观察到肾功能恶化。给药后 2 小时血清非布司他浓度，40mg 剂量组为 891.8±285.0ng/ml（均值±SE），60mg 剂量组为 770.6±242.7ng/ml（p=0.80，非配对 t 检验），表明肾功能损害患者无蓄积。未观察到非布司他相关不良反应。无患者发生进展性 TLS。
非布司他有望用于管理中度风险患者的 TLS，应进一步观察和重新评估黄嘌呤肾病。
