Hypouricemic effect and safety of febuxostat used for prevention of tumor lysis syndrome

Abstract

PurposeWe evaluated the efficacy and safety of febuxostat, a non-purine xanthine oxidase inhibitor, used for prevention of hyperuricemia associated with tumor lysis syndrome (TLS).MethodsRecords of adult patients with newly diagnosed or relapsed hematologic malignancies who received febuxostat within 7 days before initiation of chemotherapy were retrieved retrospectively at a single institute. The changes in serum uric acid levels from before and 7 days after initiation of febuxostat were evaluated and compared with the historical control group of patients who received allopurinol. We also evaluated non-hematological adverse events during the study period.ResultsA total of 78 patients’ records were analyzed, 38 in the febuxostat group and 39 in the allopurinol group. There were no significant differences in the incidence of treatment failure, defined as development of clinical TLS or receiving rasburicase, between the febuxostat and allopurinol group (5.2% vs 5.1%, P>0.99). The mean serum uric acid levels were significantly decreased, compared to the baseline (5.6 ± 2.1 mg/dL), at 7 days after initiation of febuxostat (3.1 ± 1.5 mg/dL, last observation carried forward, P<0.001). There were no statistically significant differences in the percent change in the serum uric acid levels between the 40 mg/day febuxostat and the 300 mg/day allopurinol groups (P = 0.57). Grade 3–4 liver dysfunctions were observed in both the febuxostat and allopurinol groups, without significant differences in incidence between the two groups (2.6% vs 5.1%, P>0.99). Neither gout flare nor skin rash occurred in any patients.ConclusionsFebuxostat is feasible for prevention of hyperuricemia associated with TLS.

Febuxostat administration for the prevention of tumour lysis syndrome: A meta‐analysis

“…The most important methodological characteristics (study design, exclusion criteria, population and disease type, criteria for TLS diagnosis and response definition, timing and dosage of febuxostat and allopurinol) of the included studies are described in Table . Three studies were RCTs, while the rest 3 were observational with a cohort design . Patients with severe kidney impairment were excluded from the majority of the studies.…”

“…Six studies [22][23][24][25][26][27] were finally included in the present review, with a total of 659 patients. Among them, 331 were treated with febuxostat, while allopurinol was administered in the rest 328 patients.…”

“…Three studies were RCTs, 23,24,26 while the rest 3 were observational with a cohort design. 22,25,27 Patients with severe kidney impairment were excluded from the majority of the studies. The population consisted exclusively of adults in 4 studies, while one study included only paediatric patients 27 and another one had no age limitations.…”

Toward an Understanding of Structural Insights of Xanthine and Aldehyde Oxidases: An Overview of their Inhibitors and Role in Various Diseases

“…Circulating XO is an indicator of hepatic and intestinal damage, and can also acts as a circulating mediator that is accountable for remote organ injury in a variety of pathophysiological conditions. 42 The higher expression of XO also leads to inflammation, [70][71][72] metabolic disorder, 59 diabetes, 73 chronic heart failure, [74][75][76] hypertension, 77,78 cardiovascular diseases, 77,79,80 renal disease, 81 ischemia-reperfusion damage, 70,82 atherosclerosis, 83 dementia, 84 schizophrenia, 85 carcinogenesis, 14,15 endothelial dysfunction, 71,86 tumor lysis syndrome, 87,88 atrial fibrillation, 89 and circulatory shock. XO abets the oxidation/hydroxylation of numerous purines, pterins, aromatic heterocycles, aliphatic and aromatic aldehydes, thereby assist in the detoxification or activation of endogenous compounds and it also plays a vital role in the drug metabolism.…”

Managing Tumor Lysis Syndrome in the Era of Novel Cancer Therapies

“…Bendamustine carries a warning against the concomitant use of allopurinol because of severe skin reactions (such as Stevens-Johnson syndrome; Teva Pharmaceutical Industries Ltd., 2016). Recently, febuxostat was shown to reduce elevated uric acid levels associated with TLS, with efficacy comparable (Maie et al, 2014) or superior to allopurinol (Spina et al, 2015).…”