M Spina1, Z Nagy2, J M Ribera3, M Federico4, I Aurer5, K Jordan6, G Borsaru7, A S Pristupa8, A Bosi9, S Grosicki10, N L Glushko11, D Ristic12, J Jakucs13, P Montesinos14, J Mayer15, E M Rego16, S Baldini17, S Scartoni17, A Capriati17, C A Maggi17, C Simonelli17. 1. Division of Medical Oncology A, National Cancer Institute, Aviano, Italy mspina@cro.it. 2. First Department of Medicine, Semmelweis University Medical School, Budapest, Hungary. 3. ICO-Hospital Germans Trias i Pujol, Jose Carreras Research Institute, UAB, Badalona, Spain. 4. Department of Diagnostic, Clinical and Public Health Medicine, University of Modena and Reggio Emilia, Modena, Italy. 5. University Hospital Centre Zagreb and Medical School, Zagreb, Croatia. 6. Department of Hematology and Oncology, Martin Luther University Halle-Wittenberg, Halle, Germany. 7. Department of Hematology, "Coltea" Clinical Hospital, Bucharest, Romania. 8. Department of Hematology, Ryazan Regional Clinical Hospital, Ryazan, Russia. 9. Hematology Unit, Azienda Ospedaliero Universitaria Careggi, University of Florence, Florence, Italy. 10. Department of Cancer Prevention, Faculty of Public Health, Silesian Medical University in Katowice, Katowice, Poland. 11. Department of Hematology, Ivano-Frankivsk Regional Clinical Hospital, Ivano-Frankivsk, Ukraine. 12. Institute for Oncology and Radiology of Serbia, Belgrade, Serbia. 13. First Department of Internal Medicine Endocrinology and Hematology, Pandy Kalman Megyei Korhaz, Gyula, Hungary. 14. Department of Hematology, Hospital Universitario La Fe, Valencia, Spain. 15. Department of Internal Medicine, Hematology and Oncology, University Hospital Brno, Brno, Czech Republic. 16. Hospital das Clinicas da Faculdade de Medicina de Ribeirão Preto-USP, Ribeirão Preto, Brazil. 17. Department of Clinical Research, Menarini Ricerche, Firenze, Italy.
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.
RCT Entities:
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 Joannidis; S J Klein; S John; M Schmitz; D Czock; W Druml; A Jörres; D Kindgen-Milles; J T Kielstein; M Oppert; V Schwenger; C Willam; A Zarbock Journal: Med Klin Intensivmed Notfmed Date: 2018-03-28 Impact factor: 0.840