A Phase 2 study of perifosine in advanced or metastatic breast cancer
A Phase 2 study of perifosine in advanced or metastatic breast cancer
复制标题
DOI：
10.1007/s10549-007-9584-x
复制
发表时间：
2008-03-01
影响因子：
3.8
通讯作者：
Moor, Malcolm J.
中科院分区：
文献类型：
--
作者：
Leighl, Natasha B.;Dent, Susan;Moor, Malcolm J.
蒽环类和紫杉烷类一线和二线化疗治疗转移性乳腺癌可适度提高生存率，但有潜在的显著毒性。后续化疗的反应率为20- 25%，对生存率的影响未知。派立福新是一种口服烷基磷脂，结构上与米替福新相关，对乳腺癌细胞系和异种移植模型具有显着的活性，具有广谱细胞效应。目的确定派立福新对晚期疾病既往最多2线化疗后的转移性乳腺癌患者的疗效和毒性。方法入组18例患者，其中17例接受治疗，采用负荷/维持剂量方案，第1天300 mg，第2-21天维持150 mg，每28 d 1次，直至疾病进展或出现不可接受的毒性反应。15例患者既往至少接受过1种转移性疾病化疗方案（最多2种）。每例患者的中位周期为2个周期（范围1-13）。16例缓解可评价：2例SD持续4个周期，1例SD持续13个周期，13例进展至第2周期。3/4级药物相关非血液学毒性包括：腹泻（2）、呕吐（2）、恶心（2）、疲乏（2）和厌食（1）。未观察到3/4级血液学毒性。中位进展时间为8周（7-15周）。结论本组转移性乳腺癌患者经预治疗后无客观缓解。在2个月时观察到19%的患者病情稳定。
Background First- and second-line chemotherapy with anthracyclines and taxanes in metastatic breast cancer yield a modest improvement in survival with potentially significant toxicity. Subsequent lines of chemotherapy yield response rates of 20-25%, with an unknown impact on survival. Perifosine, an oral alkylphospholipid structurally related to miltefosine, has marked activity against breast cancer cell lines and xenograft models, with broad spectrum cellular effects.Objectives To determine the efficacy and toxicity of perifosine in patients with metastatic breast cancer patients after up to 2 lines of prior chemotherapy for advanced disease.Methods 18 patients were enrolled, and 17 treated, using a loading/maintenance dose schedule, (day 1, 300 mg, maintenance 150 mg days 2-21) every 28 days, until disease progression or unacceptable toxicity.Results Median age of patients was 54 (28-69), 16/17 were female, ECOG performance status was 0/1 in 16 patients. Fifteen received at least 1 prior chemotherapy regimen for metastatic disease (maximum 2). A median of 2 cycles (range 1-13) was administered per patient. Sixteen were evaluable for response: 2 had SD for 4 cycles, 1 SD for 13 cycles, 13 progressed by cycle 2. Grade 3/4 drug-related non-hematologic toxicities include: diarrhea (2), vomiting (2), nausea (2), fatigue (2) and anorexia (1). No grade 3/4 hematologic toxicities were seen. Median time to progression was 8 weeks (7-15 weeks).Conclusion No objective responses were seen in this group of pretreated metastatic breast cancer patients. Disease stabilization was observed in 19% at 2 months.