AIM: To identify the maximum-tolerated dose (MTD) and pharmacokinetics of oral perifosine. METHODS: Patients with solid tumours received perifosine at dosages ranging from 100-800mg/week. Eligibility criteria included life expectancy>12weeks, WHO performance status2, normal blood, liver and renal functions and no recent anticancer treatment. Drug concentrations were analysed by HPLC-MS/MS. RESULTS: Thirty six patients were recruited (75% males, mean age 54.7years, performance status 1 in 72.2%). Adverse events included nausea (69.4%), diarrhoea (55.6%), vomiting (52.8%) and abdominal pain (13.9%). Antiemetic regimens including glucocorticoids, dopamine antagonists and 5-HT3-antagonists were used as treatment and/or prophylaxis in 50% of the patients. Though MTD was formally not reached with 800mg/week, the treatment discontinuation due to diarrhoea and vomiting likely related to perifosine in two cases led to the decision to stop further dose escalation. Pharmacokinetics after a single dose were median t(max)=8.0-24.2h, median t(1/2)=81.0-115.9h and mean(geo) CL/f=0.28-0.43mL/min/kg. Urinary excretion was below 1%. Perifosine slightly accumulated and steady state was nearly reached after 2-3weeks. CONCLUSION: Oral perifosine was tolerable up to 600mg/week in cancer patients when administered with meal and prophylactic antiemetics. Based on its half-life of about 4days, a weekly regimen may be appropriate. Copyright 2010 Elsevier Ltd. All rights reserved.
AIM: To identify the maximum-tolerated dose (MTD) and pharmacokinetics of oral perifosine. METHODS:Patients with solid tumours received perifosine at dosages ranging from 100-800mg/week. Eligibility criteria included life expectancy>12weeks, WHO performance status2, normal blood, liver and renal functions and no recent anticancer treatment. Drug concentrations were analysed by HPLC-MS/MS. RESULTS: Thirty six patients were recruited (75% males, mean age 54.7years, performance status 1 in 72.2%). Adverse events included nausea (69.4%), diarrhoea (55.6%), vomiting (52.8%) and abdominal pain (13.9%). Antiemetic regimens including glucocorticoids, dopamine antagonists and 5-HT3-antagonists were used as treatment and/or prophylaxis in 50% of the patients. Though MTD was formally not reached with 800mg/week, the treatment discontinuation due to diarrhoea and vomiting likely related to perifosine in two cases led to the decision to stop further dose escalation. Pharmacokinetics after a single dose were median t(max)=8.0-24.2h, median t(1/2)=81.0-115.9h and mean(geo) CL/f=0.28-0.43mL/min/kg. Urinary excretion was below 1%. Perifosine slightly accumulated and steady state was nearly reached after 2-3weeks. CONCLUSION: Oral perifosine was tolerable up to 600mg/week in cancerpatients when administered with meal and prophylactic antiemetics. Based on its half-life of about 4days, a weekly regimen may be appropriate. Copyright 2010 Elsevier Ltd. All rights reserved.
Authors: Martin Schmidt-Hieber; Robert Dabrowski; Babette Aicher; Philipp Lohneis; Antonia Busse; Carola Tietze-Buerger; Birgit Reufi; Eckhard Thiel; Igor Wolfgang Blau Journal: Invest New Drugs Date: 2011-07-13 Impact factor: 3.850
Authors: Martin Schmidt-Hieber; Robert Dabrowski; Andreas Weimann; Babette Aicher; Philipp Lohneis; Antonia Busse; Eckhard Thiel; Igor W Blau Journal: Invest New Drugs Date: 2010-11-16 Impact factor: 3.850
Authors: Siqing Fu; Bryan T Hennessy; Chaan S Ng; Zhenlin Ju; Kevin R Coombes; Judith K Wolf; Anil K Sood; Charles F Levenback; Robert L Coleman; John J Kavanagh; David M Gershenson; Maurie Markman; Kristine Dice; Adrienne Howard; Jane Li; Yang Li; Katherine Stemke-Hale; Mary Dyer; Edward Atkinson; Ed Jackson; Vikas Kundra; Razelle Kurzrock; Robert C Bast; Gordon B Mills Journal: Gynecol Oncol Date: 2012-04-06 Impact factor: 5.482
Authors: Paul G Richardson; Cathy Eng; Jill Kolesar; Teru Hideshima; Kenneth C Anderson Journal: Expert Opin Drug Metab Toxicol Date: 2012-05 Impact factor: 4.481