非布索坦
医学
别嘌呤醇
肿瘤溶解综合征
肌酐
内科学
肾功能
不利影响
泌尿科
痛风
胃肠病学
外科
尿酸
高尿酸血症
化疗
作者
Michele Spina,Zsolt Nagy,Josep‐María Ribera,Massimo Federico,Igor Aurer,Karin Jordan,Gabriela Borsaru,Alexander Pristupa,Alberto Bosi,Sebastian Grosicki,Nataliia Glushko,Dušan Ristić,János Jakucs,Pau Montesinos,Jiřı́ Mayer,Eduardo Magalhães Rego,Simone Baldini,Simona Scartoni,Angela Capriati,Carlo Alberto Maggi,Cecilia Simonelli
标识
DOI:10.1093/annonc/mdv317
摘要
BackgroundSerum uric acid (sUA) control is of key relevance in tumor lysis syndrome (TLS) prevention as it correlates with both TLS and renal event risk. We sought to determine whether febuxostat fixed dose achieves a better sUA control than allopurinol while preserving renal function in TLS prevention.Patients and methodsPatients with hematologic malignancies at intermediate to high TLS risk grade were randomized to receive febuxostat or allopurinol, starting 2 days before induction chemotherapy, for 7–9 days. Study treatment was blinded, whereas daily dose (low/standard/high containing allopurinol 200/300/600 mg, respectively, or fixed febuxostat 120 mg) depended on the investigator's choice. The co-primary end points, sUA area under curve (AUC sUA1–8) and serum creatinine change, were assessed from baseline to day 8 and analyzed through analysis of covariance with two-sided overall significance level of 5%. Secondary end points included treatment responder rate, laboratory and clinical TLS incidence and safety.ResultsA total of 346 patients (82.1% intermediate TLS risk; 82.7% assigned to standard dose) were randomized. Mean AUC sUA1–8 was 514.0 ± 225.71 versus 708.0 ± 234.42 mgxh/dl (P < 0.0001) in favor of febuxostat. Mean serum creatinine change was -0.83 ± 26.98% and -4.92 ± 16.70% for febuxostat and allopurinol, respectively (P = 0.0903). No differences among secondary efficacy end points were detected. Drug-related adverse events occurred in 6.4% of patients in both arms.ConclusionIn the largest adult trial carried out in TLS prevention, febuxostat achieved a significant superior sUA control with one fixed dose in comparison to allopurinol with comparable renal function preservation and safety profile.Clinical trial registrationNCT01724528.
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