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.

PATIENTS AND 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.

CONCLUSION:

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.

CLINICAL TRIAL REGISTRATION:

NCT01724528.

• Authors: M Spina, Z Nagy, J M Ribera, M Federico, I Aurer, K Jordan, G Borsaru, A S Pristupa, A Bosi, S Grosicki, N L Glushko, D Ristic, J Jakucs, P Montesinos, J Mayer, E M Rego, S Baldini, S Scartoni, A Capriati, C A Maggi, C Simonelli, FLORENCE Study Group
• Journal: Annals of oncology : official journal of the European Society for Medical Oncology (Ann Oncol) Vol. 26 Issue 10 Pg. 2155-61 (Oct 2015) ISSN: 1569-8041 [Electronic] England
• PMID: 26216382 (Publication Type: Clinical Trial, Phase III, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: [email protected].

Chemical References

• Gout Suppressants
• Febuxostat
• Uric Acid
• Allopurinol

Topics

• Adult
• Aged
• Aged, 80 and over
• Allopurinol (therapeutic use)
• Double-Blind Method
• Febuxostat (therapeutic use)
• Female
• Follow-Up Studies
• Gout Suppressants (therapeutic use)
• Hematologic Neoplasms (drug therapy, pathology)
• Humans
• Male
• Middle Aged
• Neoplasm Staging
• Prognosis
• Risk Factors
• Tumor Lysis Syndrome (blood, prevention & control)
• Uric Acid (blood)
• Young Adult