A randomized double-blind phase III pivotal study of febuxostat (FEB) versus allopurinol (ALL) in the prevention of tumor lysis syndrome (TLS): Florence study.

Konference: 2014 50th ASCO Annual Meeting - účast ČR

Kategorie: Podpůrná onkologická léčba, výživa nemocných a ošetřovatelská péče

Téma: Postery

Číslo abstraktu: 9641^

Autoři: M.D. Michele Spina; Prof. M.D. Zoltán Zsolt Nagy, Ph.D.; Josep-Maria Ribera; Prof. M.D. Massimo Federico; Dr. Igor Aurer; M.D. Karin Jordan, Ph.D.; Dr. Gabriela Borsaru; M.D. Alexander S. Pristupa, Ph.D.; Prof. M.D. Alberto Bosi (1950-); M.D. Sebastian Grosicki; Nataliia L. Glushko; Dusan Ristic; Dr. János Jakucs; prof. MUDr. Jiří Mayer, CSc.; Prof. M.D. Eduardo Magalhães Rego; Dr. Simone Baldini; Simona Scartoni; Cecilia Simonelli; Angela Capriati; Carlo Alberto Maggi


Background: Tumor lysis syndrome (TLS) is an oncologic emergency characterized especially by elevated serum uric acid (sUA). FEB is an orally administerd selective xanthine oxidase inhibitor to reduce sUA. 

Methods: This was a randomized, double blind phase III trial of FEB vs ALL in terms of control of sUA level and preservation of renal function in patients undergoing chemotherapy (CT) for hematologic malignancies at intermediate to high risk of TLS. Patients werestratified according to TLS risk and sUA level to FEB or ALL starting from 2 days prior CT and continued for 7-9 days. Assigned treatment was blinded, while daily dose level (low/standard/high containing ALL 200/300/600 mg or fixed FEB 120) was upon investigator’s choice. Primary endpoints were sUA area under the curve (AUC sUA1-8) and change in serum creatinine (sC) level both from baseline to Day 8, analyzed through ANCOVA including treatment and stratification factors as covariates. Secondary endpoints were response rate (sUA ≤ 7.5 mg/dL from CT start to Day 8), incidence of laboratory and clinical TLS and safety. The study was run in 79 sites in Europe and Brazil (NCT01724528). 

Results: 346 patients were included with similar baseline demographics in both groups. 82.1% of patients were at intermediate risk of TLS, 87.6% had a baseline sUA ≤ 7.5 mg/dl and 82.7% received standard dose level. Intention to treat (ITT) analysis: mean AUC sUA1-8(mgxh/dl) was significantly lower in FEB arm (514.0 ± 225.71 vs 708.0 ± 234.42; p < .0001). No significant difference in mean sC change(%) occurred between FEB and ALL arms (-0.83 ± 26.98 vs -4.92 ± 16.70 respectively, p=0.0903). No significant difference was detected among secondary efficacy endpoints. Incidence of all adverse events (AEs) and related AEs was 67.6% vs 64.7% and 6.4% vs 6.4% in FEB and ALL arm, respectively. 

Conclusions: In this largest TLS prevention trial FEB proved to be significantly superior over ALL with a 28% lower exposure to sUA during CT. As no dose adjustment of FEB in patients with preexisting mild or moderate renal impairment is necessary makes FEB a preferable preventive measure of TLS. Clinical trial information:NCT01724528.


J Clin Oncol 32:5s, 2014 (suppl; abstr 9641^)

Datum přednesení příspěvku: 1. 6. 2014