OBJECTIVES: Perifosine is an alkylphospholipid that has exhibited broad antineoplastic activity in preclinical studies. The primary objective of this study was to determine the clinical efficacy of this agent in the treatment of androgen-independent prostate cancer (AIPC) using PSA and clinical criteria. PATIENTS AND METHODS: Nineteen patients with progressive, metastatic AIPC were treated with oral perifosine. Cycles were 28 days in length. A loading dose of 900 mg was given on day 1 of cycle 1 followed by a maintenance dose of 150 mg daily for the next 20 days. A loading dose of 600 mg was administered on the first day of subsequent cycles by the maintenance dose of 150 mg daily for the next 20 days. Pharmacokinetic measurements were made throughout the course of the study. Circulating epithelial cells were collected via leukapheresis on day 0, 3, and 28. RESULTS: Median patient age was 67 years and median PSA was 180 ng/mL (range: 19-904 ng/ml). Grade 1-2 fatigue and gastrointestinal toxicities were common. Pharmacokinetic studies showed an average minimum concentration at steady-state of approximately 4059 ng/ml which correlated well with previous studies. Median time to progression was four weeks. There were no radiographic responses or PSA declines of 50% or greater related to perifosine. CONCLUSIONS: Treatment with perifosine was complicated by fatigue and gastrointestinal toxicity. No significant clinical activity against prostate cancer was observed. This agent does not merit further study in the setting of monotherapy in this population.
OBJECTIVES:Perifosine is an alkylphospholipid that has exhibited broad antineoplastic activity in preclinical studies. The primary objective of this study was to determine the clinical efficacy of this agent in the treatment of androgen-independent prostate cancer (AIPC) using PSA and clinical criteria. PATIENTS AND METHODS: Nineteen patients with progressive, metastatic AIPC were treated with oral perifosine. Cycles were 28 days in length. A loading dose of 900 mg was given on day 1 of cycle 1 followed by a maintenance dose of 150 mg daily for the next 20 days. A loading dose of 600 mg was administered on the first day of subsequent cycles by the maintenance dose of 150 mg daily for the next 20 days. Pharmacokinetic measurements were made throughout the course of the study. Circulating epithelial cells were collected via leukapheresis on day 0, 3, and 28. RESULTS: Median patient age was 67 years and median PSA was 180 ng/mL (range: 19-904 ng/ml). Grade 1-2 fatigue and gastrointestinal toxicities were common. Pharmacokinetic studies showed an average minimum concentration at steady-state of approximately 4059 ng/ml which correlated well with previous studies. Median time to progression was four weeks. There were no radiographic responses or PSA declines of 50% or greater related to perifosine. CONCLUSIONS: Treatment with perifosine was complicated by fatigue and gastrointestinal toxicity. No significant clinical activity against prostate cancer was observed. This agent does not merit further study in the setting of monotherapy in this population.
Authors: Sanjay N Mediwala; Huiying Sun; Adam T Szafran; Sean M Hartig; Guru Sonpavde; Teresa G Hayes; Perumal Thiagarajan; Michael A Mancini; Marco Marcelli Journal: Prostate Date: 2012-07-20 Impact factor: 4.104
Authors: Edward W Howard; Steve C L Leung; H F Yuen; Chee Wai Chua; Davy T Lee; K W Chan; Xianghong Wang; Yong Chuan Wong Journal: Clin Exp Metastasis Date: 2008-03-14 Impact factor: 5.150