A phase 1-2 study of a farnesyltransferase inhibitor, tipifarnib, combined with idarubicin and cytarabine for patients with newly diagnosed acute myeloid leukemia and high-risk myelodysplastic syndrome.
A phase 1-2 study of a farnesyltransferase inhibitor, tipifarnib, combined with idarubicin and cytarabine for patients with newly diagnosed acute myeloid leukemia and high-risk myelodysplastic syndrome.
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DOI：
10.1002/cncr.25575
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发表时间：
2011-03-15
期刊：
影响因子：
6.2
通讯作者：
Cortes, Jorge
中科院分区：
文献类型：
--
作者：
Jabbour, Elias;Kantarjian, Hagop;Ravandi, Farhad;Garcia-Manero, Guillermo;Estrov, Zeev;Verstovsek, Srdan;O'Brien, Susan;Faderl, Stefan;Thomas, Deborah A.;Wright, John J.;Cortes, Jorge
关键词：
作者对 95 名既往未经治疗的急性髓系白血病 (AML) 或高危骨髓增生异常综合征患者进行了替比法尼联合伊达比星和阿糖胞苷 (IA) 的 1/2 期研究。诱导包括第 1-3 天每天 12 mg/m2 伊达比星、第 1-4 天（如果年龄≥60 岁，则为第 1-3 天）每天连续静脉注射阿糖胞苷 1.5 g/m2 和替比法尼，第一组 (n = 6) 每天两次口服 200 mg，所有其他组每 28 天每天两次口服 300 mg，持续 21 天。巩固治疗包括第 1-2 天每天 8 mg/m2 伊达比星 5 个疗程，第 1-3 天每天 0.75 g/m2 阿糖胞苷，以及替比法尼 300 mg 每天两次，每 4-6 周 14 天。替比法尼 300 mg 每天两次，每 4-6 周一次，持续 21 天，持续 6 个月。中位随访时间为 33 个月，61 名患者实现完全缓解 (CR) (64%)，9 名患者实现完全缓解但血小板不完全恢复 (CRp) (9%)。未达到 CR 的中位持续时间。中位总生存期为 17 个月。最常见的 3 级不良事件是胃肠道毒性、肝功能障碍和皮疹。与历史 IA 相比，IA 和替比法尼在 5/7 号染色体异常患者中表现出更好的 CR 持续时间 (P = .04) 和更高的 CR 率趋势。 IA 和替比法尼的组合是安全且有效的。需要进一步研究探索不同的剂量和方案，特别是对于低危 AML 患者。
The authors conducted a phase 1/2 study of tipifarnib in combination with idarubicin and cytarabine (IA) in 95 patients with previously untreated acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome. Induction consisted of idarubicin 12 mg/m2 a day on days 1-3, cytarabine 1.5 g/m2 intravenously continuously daily on days 1-4 (days 1-3 if age ≥60 years), and tipifarnib, with the first cohort (n = 6) receiving 200 mg orally twice a day and all others receiving 300 mg twice a day for 21 days every 28 days. Consolidation consisted of 5 courses of idarubicin 8 mg/m2 a day on days 1-2, cytarabine 0.75 g/m2 a day on days 1-3, and tipifarnib 300 mg twice a day for 14 days every 4-6 weeks. Maintenance with tipifarnib 300 mg twice a day for 21 days every 4-6 weeks was continued for 6 months. With a median follow-up of 33 months, 61 patients achieved complete remission (CR) (64%), and 9 achieved complete remission with incomplete platelet recovery (CRp) (9%). The median duration of CR was not reached. Median overall survival was 17 months. The most common grade 3 adverse events were gastrointestinal toxicities, liver dysfunction, and skin rash. Compared with historical IA, IA and tipifarnib showed a better CR duration (P = .04) and a trend toward a higher CR rate in patients with chromosome 5/7 abnormalities. The combination of IA and tipifarnib is safe and active. Further studies exploring different dosages and schedules are warranted, particularly in patients with poor-risk AML.
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