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


OBJECTIVE
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).


CONCLUSIONS
No objective responses were seen in this group of pretreated metastatic breast cancer patients. Disease stabilization was observed in 19% at 2 months.
Leighl
Natasha B
NB
Medical Oncology, Princess Margaret Hospital/University Health Network, Toronto, ON, Canada. Natasha.Leighl@uhn.on.ca
Dent
Susan
S
Clemons
Mark
M
Vandenberg
Theodore A
TA
Tozer
Richard
R
Warr
David G
DG
Crump
R Michael
RM
Hedley
David
D
Pond
Gregory R
GR
Dancey
Janet E
JE
Moore
Malcolm J
MJ
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D010767:Phosphorylcholine; C105905:perifosine