A Phase 2 study of perifosine in advanced or metastatic breast cancer

Breast Cancer Res Treat. 2008 Mar;108(1):87-92. doi: 10.1007/s10549-007-9584-x. Epub 2007 Apr 26.


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.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / mortality
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Middle Aged
  • Phosphorylcholine / analogs & derivatives*
  • Phosphorylcholine / therapeutic use
  • Treatment Outcome


  • Antineoplastic Agents
  • Phosphorylcholine
  • perifosine