TY - JOUR
T1 - Efficacy and safety of febuxostat for prevention of tumor lysis syndrome in patients with malignant tumors receiving chemotherapy
T2 - a phase III, randomized, multi-center trial comparing febuxostat and allopurinol
AU - Tamura, Kazuo
AU - Kawai, Yasukazu
AU - Kiguchi, Toru
AU - Okamoto, Masataka
AU - Kaneko, Masahiko
AU - Maemondo, Makoto
AU - Gemba, Kenichi
AU - Fujimaki, Katsumichi
AU - Kirito, Keita
AU - Goto, Tetsuya
AU - Fujisaki, Tomoaki
AU - Takeda, Kenji
AU - Nakajima, Akihiro
AU - Ueda, Takanori
N1 - Publisher Copyright:
© 2016, Japan Society of Clinical Oncology.
PY - 2016/10/1
Y1 - 2016/10/1
N2 - 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.
AB - 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.
KW - Allopurinol
KW - Febuxostat
KW - Hyperuricemia
KW - Randomized clinical trial
KW - Tumor lysis syndrome
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U2 - 10.1007/s10147-016-0971-3
DO - 10.1007/s10147-016-0971-3
M3 - Article
C2 - 27017611
AN - SCOPUS:84961644341
SN - 1341-9625
VL - 21
SP - 996
EP - 1003
JO - International Journal of Clinical Oncology
JF - International Journal of Clinical Oncology
IS - 5
ER -