Leighl Natasha B, Dent Susan, Clemons Mark, Vandenberg Theodore A, Tozer Richard, Warr David G, Crump R Michael, Hedley David, Pond Gregory R, Dancey Janet E, Moore Malcolm J
Medical Oncology, Princess Margaret Hospital/University Health Network, Toronto, ON, Canada.
Breast Cancer Res Treat. 2008 Mar;108(1):87-92. doi: 10.1007/s10549-007-9584-x. Epub 2007 Apr 26.
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.
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.
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.
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).
No objective responses were seen in this group of pretreated metastatic breast cancer patients. Disease stabilization was observed in 19% at 2 months.
蒽环类药物和紫杉烷类用于转移性乳腺癌的一线及二线化疗可使生存率有适度提高，但可能伴有显著毒性。后续化疗线的缓解率为20% - 25%，对生存率的影响未知。哌立福新是一种口服烷基磷脂，在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著活性，具有广泛的细胞效应。
确定哌立福新在接受过最多2线晚期疾病前期化疗的转移性乳腺癌患者中的疗效和毒性。
招募了18名患者，17名接受治疗，采用负荷/维持剂量方案（第1天300毫克，第2 - 21天维持剂量150毫克），每28天一次，直至疾病进展或出现不可接受的毒性。
患者的中位年龄为54岁（28 - 69岁），17名患者中有16名女性，16名患者的东部肿瘤协作组（ECOG）体能状态为0/1。15名患者接受过至少1种转移性疾病的前期化疗方案（最多2种）。每位患者接受的中位周期数为2个周期（范围1 - 13个周期）。16名患者可评估疗效：2名患者疾病稳定4个周期，1名患者疾病稳定13个周期，13名患者在第2个周期时疾病进展。3/4级与药物相关的非血液学毒性包括：腹泻（2例）、呕吐（2例）、恶心（2例）、疲劳（2例）和厌食（1例）。未观察到3/4级血液学毒性。中位疾病进展时间为8周（7 - 15周）。
在这组经预处理的转移性乳腺癌患者中未观察到客观缓解。2个月时观察到19%的患者疾病稳定。
