Karp Judith E, Smith B Douglas, Gojo Ivana, Lancet Jeffrey E, Greer Jacqueline, Klein Maureen, Morris Larry, Levis Mark J, Gore Steven D, Wright John J, Garrett-Mayer Elizabeth
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD 21231-1000, USA.
Clin Cancer Res. 2008 May 15;14(10):3077-82. doi: 10.1158/1078-0432.CCR-07-4743.
Acute myelogenous leukemia (AML) does not have a high cure rate, particularly in patients with poor-risk features. Such patients might benefit from additional therapy in complete remission (CR). Tipifarnib is an oral farnesyltransferase inhibitor with activity in AML. We conducted a phase II trial of maintenance tipifarnib monotherapy for 48 adults with poor-risk AML in first CR.
Tipifarnib 400 mg twice daily for 14 of 21 days was initiated after recovery from consolidation chemotherapy, for a maximum of 16 cycles (48 weeks).
Twenty (42%) patients completed 16 cycles, 24 (50%) were removed from study for relapse, and 4 (8%) discontinued drug prematurely for intolerance. Nonhematologic toxicities were rare, but tipifarnib dose was reduced in 58% for myelosuppression. Median disease-free survival (DFS) was 13.5 months (range, 3.5-59+ months), with 30% having DFS >2 years. Comparison of CR durations for 25 patients who received two-cycle timed sequential therapy followed by tipifarnib maintenance with 23 historically similar patients who did not receive tipifarnib showed that tipifarnib was associated with DFS prolongation for patients with secondary AML and adverse cytogenetics.
This study suggests that some patients with poor-risk AML, including patients with secondary AML and adverse cytogenetics, may benefit from tipifarnib maintenance therapy. Future studies are warranted to examine alternative tipifarnib dosing and continuation beyond 16 cycles.
急性髓系白血病（AML）的治愈率不高，尤其是具有不良风险特征的患者。这类患者在完全缓解（CR）期可能会从额外的治疗中获益。替匹法尼是一种口服法尼基转移酶抑制剂，对AML有活性。我们对48例首次CR的具有不良风险AML的成人患者进行了替匹法尼维持单药治疗的II期试验。
在巩固化疗恢复后，开始使用替匹法尼400mg，每日两次，共21天中的14天，最多进行16个周期（48周）。
20例（42%）患者完成了16个周期，24例（50%）因复发退出研究，4例（8%）因不耐受提前停药。非血液学毒性罕见，但58%的患者因骨髓抑制而降低了替匹法尼剂量。中位无病生存期（DFS）为13.5个月（范围3.5 - 59 +个月），30%的患者DFS>2年。对25例接受两周期定时序贯治疗后接受替匹法尼维持治疗的患者与23例历史上未接受替匹法尼治疗的类似患者的CR持续时间进行比较，结果显示替匹法尼与继发性AML和不良细胞遗传学患者的DFS延长相关。
本研究表明，一些具有不良风险AML的患者，包括继发性AML和不良细胞遗传学患者，可能从替匹法尼维持治疗中获益。未来有必要进行研究，以探讨替匹法尼的替代给药方案以及超过16个周期的持续治疗。
