title: Efficacy and safety of febuxostat for prevention of tumor lysis syndrome in patients with malignant tumors receiving chemotherapy: a phase III, randomized, multi-center trial comparing febuxostat and allopurinol.
abstract: BACKGROUND
  Control of serum uric acid (sUA) levels is very important during chemotherapy in patients with malignant tumors, as the risks of tumor lysis syndrome (TLS) and renal events are increased with increasing levels of sUA. We investigated the efficacy and safety of febuxostat, a potent non-purine xanthine oxidase inhibitor, compared with allopurinol for prevention of hyperuricemia in patients with malignant tumors, including solid tumors, receiving chemotherapy in Japan.
  
  
  METHODS
  An allopurinol-controlled multicenter, open-label, randomized, parallel-group comparative study was carried out. Patients with malignant tumors receiving chemotherapy, who had an intermediate risk of TLS or a high risk of TLS and were not scheduled to be treated with rasburicase, were enrolled and then randomized to febuxostat (60 mg/day) or allopurinol (300 or 200 mg/day). All patients started to take the study drug 24 h before chemotherapy. The primary objective was to confirm the non-inferiority of febuxostat to allopurinol based on the area under the curve (AUC) of sUA for a 6-day treatment period.
  
  
  RESULTS
  Forty-nine and 51 patients took febuxostat and allopurinol, respectively. sUA decreased over time after initiation of study treatment. The least squares mean difference of the AUC of sUA between the treatment groups was -33.61 mg h/dL, and the 95 % confidence interval was -70.67 to 3.45, demonstrating the non-inferiority of febuxostat to allopurinol. No differences were noted in safety outcomes between the treatment groups.
  
  
  CONCLUSIONS
  Febuxostat demonstrated an efficacy and safety similar to allopurinol in patients with malignant tumors receiving chemotherapy.
  
  
  BACKGROUND
  http://www.clinicaltrials.jp ; Identifier: JapicCTI-132398.
authors.affiliation: General Medical Research Center, Fukuoka University, Fukuoka, Fukuoka, Japan. ktamura@fukuoka-u.ac.jp.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tamura
authors.affiliation: Department of Hematology and Oncology, Fukui Prefectural Hospital, Fukui, Fukui, Japan.
authors.forename: Yasukazu
authors.initials: Y
authors.lastname: Kawai
authors.affiliation: Division of Hematology, Chugoku Central Hospital, Fukuyama, Hiroshima, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Kiguchi
authors.affiliation: Department of Hematology and Medical Oncology, Fujita Health University Hospital, Toyoake, Aichi, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Okamoto
authors.affiliation: Department of Internal Medicine, Uwajima City Hospital, Uwajima, Ehime, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Kaneko
authors.affiliation: Department of Respiratory Medicine, Miyagi Cancer Center, Natori, Miyagi, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Maemondo
authors.affiliation: Department of Respiratory Medicine, Chugoku Central Hospital, Fukuyama, Hiroshima, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Gemba
authors.affiliation: Department of Hematology, Fujisawa City Hospital, Fujisawa, Kanagawa, Japan.
authors.forename: Katsumichi
authors.initials: K
authors.lastname: Fujimaki
authors.affiliation: Department of Hematology and Oncology, University of Yamanashi, Chuo, Yamanashi, Japan.
authors.forename: Keita
authors.initials: K
authors.lastname: Kirito
authors.affiliation: Department of Internal Medicine, Tokushima Red Cross Hospital, Komatsushima, Tokushima, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Goto
authors.affiliation: Department of Internal Medicine, Matsuyama Red Cross Hospital, Matsuyama, Ehime, Japan.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Fujisaki
authors.affiliation: Pharmaceutical Development Department I, Teijin Pharma Limited, Chiyoda, Tokyo, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Takeda
authors.affiliation: Pharmaceutical Development Administration Department, Teijin Pharma Limited, Chiyoda, Tokyo, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Nakajima
authors.affiliation: Department of Hematology and Oncology, Faculty of Medical Sciences, University of Fukui, Fukui, Fukui, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Ueda
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000493:Allopurinol / Q000627:therapeutic use; D000069465:Febuxostat / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006073:Gout; D006074:Gout Suppressants / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D033461:Hyperuricemia / Q000517:prevention & control; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy; D013844:Thiazoles / Q000627:therapeutic use; D015275:Tumor Lysis Syndrome / Q000097:blood / Q000517:prevention & control*; D014527:Uric Acid / Q000097:blood; D014969:Xanthine Oxidase; D055815:Young Adult
chemical_list: D006074:Gout Suppressants; D013844:Thiazoles; D000069465:Febuxostat; D014527:Uric Acid; D000493:Allopurinol; D014969:Xanthine Oxidase
keywords: Allopurinol; Febuxostat; Hyperuricemia; Randomized clinical trial; Tumor lysis syndrome