Kazuo Tamura1, Yasukazu Kawai2, Toru Kiguchi3, Masataka Okamoto4, Masahiko Kaneko5, Makoto Maemondo6, Kenichi Gemba7, Katsumichi Fujimaki8, Keita Kirito9, Tetsuya Goto10, Tomoaki Fujisaki11, Kenji Takeda12, Akihiro Nakajima13, Takanori Ueda14. 1. General Medical Research Center, Fukuoka University, Fukuoka, Fukuoka, Japan. ktamura@fukuoka-u.ac.jp. 2. Department of Hematology and Oncology, Fukui Prefectural Hospital, Fukui, Fukui, Japan. 3. Division of Hematology, Chugoku Central Hospital, Fukuyama, Hiroshima, Japan. 4. Department of Hematology and Medical Oncology, Fujita Health University Hospital, Toyoake, Aichi, Japan. 5. Department of Internal Medicine, Uwajima City Hospital, Uwajima, Ehime, Japan. 6. Department of Respiratory Medicine, Miyagi Cancer Center, Natori, Miyagi, Japan. 7. Department of Respiratory Medicine, Chugoku Central Hospital, Fukuyama, Hiroshima, Japan. 8. Department of Hematology, Fujisawa City Hospital, Fujisawa, Kanagawa, Japan. 9. Department of Hematology and Oncology, University of Yamanashi, Chuo, Yamanashi, Japan. 10. Department of Internal Medicine, Tokushima Red Cross Hospital, Komatsushima, Tokushima, Japan. 11. Department of Internal Medicine, Matsuyama Red Cross Hospital, Matsuyama, Ehime, Japan. 12. Pharmaceutical Development Department I, Teijin Pharma Limited, Chiyoda, Tokyo, Japan. 13. Pharmaceutical Development Administration Department, Teijin Pharma Limited, Chiyoda, Tokyo, Japan. 14. Department of Hematology and Oncology, Faculty of Medical Sciences, University of Fukui, Fukui, Fukui, Japan.
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. CONCLUSION:Febuxostat demonstrated an efficacy and safety similar to allopurinol in patients with malignant tumors receiving chemotherapy. TRIAL REGISTRY: http://www.clinicaltrials.jp ; Identifier: JapicCTI-132398.
RCT Entities:
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. CONCLUSION:Febuxostat demonstrated an efficacy and safety similar to allopurinol in patients with malignant tumors receiving chemotherapy. TRIAL REGISTRY: http://www.clinicaltrials.jp ; Identifier: JapicCTI-132398.
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