Febuxostat for management of tumor lysis syndrome including its effects on levels of purine metabolites in patients with hematological malignancies - a single institution's, pharmacokinetic and pilot prospective study

Anticancer Res. 2014 Dec;34(12):7287-96.

Abstract

Background/aim: Tumor lysis syndrome (TLS) is a life-threatening oncological emergency, and control of serum uric acid level (S-UA) is most important. In this single-institution, short-term and pilot prospective study, the efficacy of a new xanthine oxidase inhibitor, febuxostat, as an alternative to conventional allopurinol, including its effects on hypoxanthine and xanthine, was evaluated in 10 consecutive patients with hematological malignancies at intermediate risk for TLS.

Patients and methods: Febuxostat at 40 mg (n=7) or 60 mg (n=3) daily was administered according to renal function, and induction chemotherapy was started within 24 h. The primary end-point was the reduction of S-UA to ≤ 7.5 mg/dl by day 5.

Results: The median S-UA at base-line was 8.0 mg/dl (range=3.2-10.6 mg/dl). The median S-UA on day 5 after chemotherapy was 3.3 mg/dl (range=1.1-5.8 mg/dl) (p<0.0001, by paired t-test), indicating successful control of S-UA during chemotherapy. All patients achieved S-UA ≤ 7.5 mg/dl. A simultaneous decrease in serum creatinine and increase in estimated glomerular filtration rate were seen. Serum hypoxanthine and xanthine levels (as the consequence of inhibition of xanthine oxidase) were elevated along with the decrease in S-UA. Xanthine level was elevated higher compared to hypoxanthine level and reached the level reported to cause xanthine nephropathy, but no advance of renal impairment was observed. Serum febuxostat concentrations at 2 h after administration were 891.8 ± 285.0 ng/ml (mean ± SE) for the 40-mg dose and 770.6 ± 242.7 ng/ml for the 60-mg dose (p=0.80, unpaired t-test), showing no accumulation in patients with renal impairment. No febuxostat-related adverse reactions were noted. No patients experienced progressive TLS.

Conclusion: Febuxostat is promising for the management of TLS of an intermediate-risk patient and further observation and reevaluation regarding xanthine nephropathy should be performed.

Keywords: Tumor lysis syndrome; chemotherapy; febuxostat; hematological malignancy; hyperuricemia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Allopurinol / therapeutic use
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use
  • Creatinine / blood
  • Enzyme Inhibitors / administration & dosage
  • Enzyme Inhibitors / adverse effects
  • Enzyme Inhibitors / pharmacokinetics*
  • Febuxostat
  • Female
  • Glomerular Filtration Rate / drug effects
  • Hematologic Neoplasms / drug therapy*
  • Humans
  • Hypoxanthine / blood
  • Male
  • Middle Aged
  • Pilot Projects
  • Prospective Studies
  • Thiazoles / administration & dosage
  • Thiazoles / pharmacokinetics*
  • Tumor Lysis Syndrome / drug therapy
  • Tumor Lysis Syndrome / prevention & control*
  • Uric Acid / blood*
  • Xanthine / blood
  • Xanthine Oxidase / antagonists & inhibitors*

Substances

  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Thiazoles
  • Febuxostat
  • Xanthine
  • Uric Acid
  • Hypoxanthine
  • Allopurinol
  • Creatinine
  • Xanthine Oxidase

Associated data

  • JPRN/UMIN000007538