Téma: Infectious diseases, supportive care (Poster)
Číslo abstraktu: P586
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; Pau Montesinos; MD Halyna Pylypenko; prof. MUDr. Jiří Mayer, CSc.; Prof. M.D. Eduardo Magalhães Rego; Isabella Otranto; Dr. Cristina Rossi; Alessandra Scordari; Dr. Simone Baldini; Simona Scartoni; Cecilia Simonelli; Angela Capriati; Carlo Alberto Maggi
Background: The risk of tumor lysis syndrome (TLS) and renal events increases by 1.75 and 2.21 fold respectively for every mg/dl increase of serum uric acid (sUA)1, thus a better control of sUA exposure during chemotherapy (CT) is beneficial for patients.
Aims: To compare Febuxostat with Allopurinol in terms of sUA exposure control and renal function impairment prevention in patients undergoing CT for hematologic malignancies at intermediate to high risk of TLS (as per TLS expert panel risk stratification2)
Methods: This was a double-blind randomized controlled trial. 346 patients providing written informed consent were stratified according to TLS risk (intermediate vs high) and sUA level (≤ 7.5 mg/dl vs > 7.5 mg/dl) and randomized in a 1:1 ratio to receive either Febuxostat or Allopurinol for 7-9 days starting from 2 days prior CT. Dose level was upon investigator’s choice among low, standard and high containing either Allopurinol 200, 300 and 600 mg daily or fixed Febuxostat 120 mg daily. Primary endpoints were sUA area under the curve (AUC sUA1-8) and change in serum creatinine level from baseline to Day 8. Secondary endpoints were response rate (sUA ≤ 7.5 mg/dL from the start of CT to Day 8), incidence of laboratory and clinical TLS and safety. The study was performed in 79 sites in Europe and Brazil (NCT01724528).
Results: Baseline demography was similar in both groups. In Febuxostat arm there was a slightly higher number of acute leukemias (n=34 vs 25) and lymphomas (n=59 vs 54) and a slightly lower number of chronic lymphoid leukemias (n=80 vs 94). The majority of patients were at intermediate risk of TLS (82.1%, n=284), had a baseline sUA ≤ 7.5 mg/dl (87.6%, n=303) and received standard dose therapy (82.7%, n=286). Mean AUC sUA1-8 was significantly lower in the Febuxostat arm (514.0 ± 225.71 mg x h/dl vs 708.0 ± 234.42 mg x h/dl, p < .0001). There were no significant differences between the Febuxostat and Allopurinol arms in mean change in serum creatinine (-0.83 ± 26.98% vs -4.92 ± 16.70%, p=0.0903) nor in secondary efficacy endpoints. Incidence of all adverse events (AEs) and related AEs was 67.6% and 6.4% vs 64.7% and 6.4% in the Febuxostat and Allopurinol arms respectively.
Summary/Conclusion: This is the largest trial every performed comparing different TLS prevention methods. Febuxostat showed a significant 28% higher reduction of exposure to sUA during CT over Allopurinol with comparable renal function impairment prevention and safety profile. These results suggest that prophylaxis with Febuxostat may further reduce the risk of TLS development in patients with hematological malignancies at intermediate to high risk of TLS in comparison to Allopurinol.
1 Coiffier B. et al, J Clin Oncol 2008; 26: 2767-2778
2 Cairo MS. et al, British J Haematol 2010; 149: 578-586
Keywords: Chemotherapy, Leukemia, Lymphoma, Tumor lysis
Datum přednesení příspěvku: 13. 6. 2014