The University of Texas M. D. Anderson Cancer Center, Department of Leukemia, Unit 428, 1515 Holcombe Blvd, Houston, TX 77030, USA.
J Clin Oncol. 2010 Jan 10;28(2):285-91. doi: 10.1200/JCO.2009.25.0209. Epub 2009 Nov 23.
Sapacitabine is an oral deoxycytidine nucleoside analog with a unique mechanism of action that is different from cytarabine.
To define the dose-limiting toxicities (DLT) and maximum-tolerated dose (MTD) of sapacitabine given orally twice daily for 7 days every 3 to 4 weeks, or twice daily for 3 days for 2 weeks (days 1 through 3 and days 8 through 10) every 3 to 4 weeks, in refractory-relapse acute leukemia and myelodysplastic syndrome (MDS). A total of 47 patients were treated in the phase I study that used a classical 3 + 3 design. Sapacitabine was escalated from 75 to 375 mg twice daily for 7 days (n = 35) and from 375 to 475 mg twice daily for 3 days on days 1 through 3 and days 8 through 10.
The DLTs with both schedules were gastrointestinal. The MTDs were 375 mg twice daily for 7 days and 425 mg twice daily for 3 days on days 1 through 3 and days 8 through 10. The recommended phase II single-agent dose schedules were 325 mg twice daily for 7 days and 425 mg twice daily for 3 days on days 1 through 3 and days 8 through 10. Responses were observed in 13 patients (28%); four were complete responses, and nine were marrow complete responses.
Sapacitabine is a new, safely administered, oral deoxycytidine analog that has encouraging activity in leukemia and MDS. Phase II studies are ongoing.
沙培利塞是一种口服脱氧胞苷核苷类似物，具有不同于阿糖胞苷的独特作用机制。
为了确定沙培利塞在难治性复发急性白血病和骨髓增生异常综合征（MDS）患者中的口服每日两次、7 天为一疗程，每 3-4 周重复（第 1 天至第 3 天和第 8 天至第 10 天）或每日两次、3 天为一疗程，每 2 周重复（第 1 天至第 3 天和第 8 天至第 10 天）的剂量限制性毒性（DLT）和最大耐受剂量（MTD）。这项 I 期研究采用经典的 3+3 设计，共纳入 47 例患者。沙培利塞的剂量从每日两次 75mg 逐渐增加至 375mg（n=35），然后从每日两次 375mg 逐渐增加至 475mg，第 1 天至第 3 天和第 8 天至第 10 天每日两次。
两种方案的 DLT 均为胃肠道毒性。MTD 为每日两次 375mg 持续 7 天，以及第 1 天至第 3 天和第 8 天至第 10 天每日两次 425mg。推荐的 II 期单药剂量方案为每日两次 325mg 持续 7 天，以及第 1 天至第 3 天和第 8 天至第 10 天每日两次 425mg。观察到 13 例患者（28%）有缓解，其中 4 例为完全缓解，9 例为骨髓完全缓解。
沙培利塞是一种新型、安全的口服脱氧胞苷类似物，在白血病和 MDS 中具有令人鼓舞的疗效。目前正在进行 II 期研究。
