期刊
CANCER
卷 126, 期 21, 页码 4800-4805出版社
WILEY
DOI: 10.1002/cncr.33156
关键词
acute myeloid leukemia; childhood; relapse
类别
资金
- Cancer Center Support Grant from the National Institutes of Health [P30 CA021765]
- American Lebanese Syrian Associated Charities
Background Novel therapies are urgently needed for pediatric patients with relapsed acute myeloid leukemia (AML). Methods To determine whether the histone deacetylase inhibitor panobinostat could be safely given in combination with intensive chemotherapy, a phase 1 trial was performed in which 17 pediatric patients with relapsed or refractory AML received panobinostat (10, 15, or 20 mg/m(2)) before and in combination with fludarabine and cytarabine. Results All dose levels were tolerated, with no dose-limiting toxicities observed at any dose level. Pharmacokinetic studies demonstrated that exposure to panobinostat was proportional to the dose given, with no associations between pharmacokinetic parameters and age, weight, or body surface area. Among the 9 patients who had sufficient (>2%) circulating blasts on which histone acetylation studies could be performed, 7 demonstrated at least 1.5-fold increases in acetylation. Although no patients had a decrease in circulating blasts after single-agent panobinostat, 8 of the 17 patients (47%), including 5 of the 6 patients treated at dose level 3, achieved complete remission. Among the 8 complete responders, 6 (75%) attained negative minimal residual disease status. Conclusions Panobinostat can be safely administered with chemotherapy and results in increased blast histone acetylation. This suggests that it should be further studied in AML.
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