title: FLORENCE: a randomized, double-blind, phase III pivotal study of febuxostat versus allopurinol for the prevention of tumor lysis syndrome (TLS) in patients with hematologic malignancies at intermediate to high TLS risk.
abstract: BACKGROUND
  Serum 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.
  
  
  METHODS
  Patients 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.
  
  
  RESULTS
  A 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.
  
  
  CONCLUSIONS
  In 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.
  
  
  BACKGROUND
  NCT01724528.
authors.affiliation: Division of Medical Oncology A, National Cancer Institute, Aviano, Italy mspina@cro.it.
authors.forename: M
authors.initials: M
authors.lastname: Spina
authors.affiliation: First Department of Medicine, Semmelweis University Medical School, Budapest, Hungary.
authors.forename: Z
authors.initials: Z
authors.lastname: Nagy
authors.affiliation: ICO-Hospital Germans Trias i Pujol, Jose Carreras Research Institute, UAB, Badalona, Spain.
authors.forename: J M
authors.initials: JM
authors.lastname: Ribera
authors.affiliation: Department of Diagnostic, Clinical and Public Health Medicine, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Federico
authors.affiliation: University Hospital Centre Zagreb and Medical School, Zagreb, Croatia.
authors.forename: I
authors.initials: I
authors.lastname: Aurer
authors.affiliation: Department of Hematology and Oncology, Martin Luther University Halle-Wittenberg, Halle, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Jordan
authors.affiliation: Department of Hematology, "Coltea" Clinical Hospital, Bucharest, Romania.
authors.forename: G
authors.initials: G
authors.lastname: Borsaru
authors.affiliation: Department of Hematology, Ryazan Regional Clinical Hospital, Ryazan, Russia.
authors.forename: A S
authors.initials: AS
authors.lastname: Pristupa
authors.affiliation: Hematology Unit, Azienda Ospedaliero Universitaria Careggi, University of Florence, Florence, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Bosi
authors.affiliation: Department of Cancer Prevention, Faculty of Public Health, Silesian Medical University in Katowice, Katowice, Poland.
authors.forename: S
authors.initials: S
authors.lastname: Grosicki
authors.affiliation: Department of Hematology, Ivano-Frankivsk Regional Clinical Hospital, Ivano-Frankivsk, Ukraine.
authors.forename: N L
authors.initials: NL
authors.lastname: Glushko
authors.affiliation: Institute for Oncology and Radiology of Serbia, Belgrade, Serbia.
authors.forename: D
authors.initials: D
authors.lastname: Ristic
authors.affiliation: First Department of Internal Medicine Endocrinology and Hematology, Pandy Kalman Megyei Korhaz, Gyula, Hungary.
authors.forename: J
authors.initials: J
authors.lastname: Jakucs
authors.affiliation: Department of Hematology, Hospital Universitario La Fe, Valencia, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Montesinos
authors.affiliation: Department of Internal Medicine, Hematology and Oncology, University Hospital Brno, Brno, Czech Republic.
authors.forename: J
authors.initials: J
authors.lastname: Mayer
authors.affiliation: Hospital das Clinicas da Faculdade de Medicina de Ribeirão Preto-USP, Ribeirão Preto, Brazil.
authors.forename: E M
authors.initials: EM
authors.lastname: Rego
authors.affiliation: Department of Clinical Research, Menarini Ricerche, Firenze, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Baldini
authors.affiliation: Department of Clinical Research, Menarini Ricerche, Firenze, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Scartoni
authors.affiliation: Department of Clinical Research, Menarini Ricerche, Firenze, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Capriati
authors.affiliation: Department of Clinical Research, Menarini Ricerche, Firenze, Italy.
authors.forename: C A
authors.initials: CA
authors.lastname: Maggi
authors.affiliation: Department of Clinical Research, Menarini Ricerche, Firenze, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Simonelli
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000493:Allopurinol / Q000627:therapeutic use*; D004311:Double-Blind Method; D000069465:Febuxostat / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006074:Gout Suppressants / Q000627:therapeutic use*; D019337:Hematologic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D012307:Risk Factors; D015275:Tumor Lysis Syndrome / Q000097:blood / Q000517:prevention & control*; D014527:Uric Acid / Q000097:blood; D055815:Young Adult
chemical_list: D006074:Gout Suppressants; D000069465:Febuxostat; D014527:Uric Acid; D000493:Allopurinol
keywords: allopurinol; febuxostat; hematologic malignancy; kidney injury; tumor lysis