title: Perifosine plus docetaxel in patients with platinum and taxane resistant or refractory high-grade epithelial ovarian cancer.
abstract: OBJECTIVE
  On the basis of reversal of taxane resistance with AKT inhibition, we initiated a phase I trial of the AKT inhibitor perifosine with docetaxel in taxane and platinum-resistant or refractory epithelial ovarian cancer.
  
  
  METHODS
  Patients with pathologically confirmed high-grade epithelial ovarian cancer (taxane resistant, n=10; taxane refractory, n=11) were enrolled. Peripheral blood samples and tumor biopsies were obtained and (18)F-FDG-PET and DCE-MRI scans were performed for pharmacodynamic and imaging studies.
  
  
  RESULTS
  Patients received a total of 42 treatment cycles. No dose-limiting toxicity was observed. The median progression-free survival and overall survival were 1.9 months and 4.5 months, respectively. One patient with a PTEN mutation achieved a partial remission (PR) for 7.5 months, and another patient with a PIK3CA mutation had stable disease (SD) for 4 months. Two other patients without apparent PI3K pathway aberrations achieved SD. Two patients with KRAS mutations demonstrated rapid progression. Decreased phosphorylated S6 correlated with (18)F-FDG-PET responses.
  
  
  CONCLUSIONS
  Patients tolerated perifosine 150 mg PO daily plus docetaxel at 75 mg/m(2) every 4 weeks. Further clinical evaluation of effects of perifosine with docetaxel on biological markers and efficacy in patients with ovarian cancer with defined PI3K pathway mutational status is warranted.
authors.affiliation: Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA. siqingfu@mdanderson.org
authors.forename: Siqing
authors.initials: S
authors.lastname: Fu
authors.forename: Bryan T
authors.initials: BT
authors.lastname: Hennessy
authors.forename: Chaan S
authors.initials: CS
authors.lastname: Ng
authors.forename: Zhenlin
authors.initials: Z
authors.lastname: Ju
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Coombes
authors.forename: Judith K
authors.initials: JK
authors.lastname: Wolf
authors.forename: Anil K
authors.initials: AK
authors.lastname: Sood
authors.forename: Charles F
authors.initials: CF
authors.lastname: Levenback
authors.forename: Robert L
authors.initials: RL
authors.lastname: Coleman
authors.forename: John J
authors.initials: JJ
authors.lastname: Kavanagh
authors.forename: David M
authors.initials: DM
authors.lastname: Gershenson
authors.forename: Maurie
authors.initials: M
authors.lastname: Markman
authors.forename: Kristine
authors.initials: K
authors.lastname: Dice
authors.forename: Adrienne
authors.initials: A
authors.lastname: Howard
authors.forename: Jane
authors.initials: J
authors.lastname: Li
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.forename: Katherine
authors.initials: K
authors.lastname: Stemke-Hale
authors.forename: Mary
authors.initials: M
authors.lastname: Dyer
authors.forename: Edward
authors.initials: E
authors.lastname: Atkinson
authors.forename: Ed
authors.initials: E
authors.lastname: Jackson
authors.forename: Vikas
authors.initials: V
authors.lastname: Kundra
authors.forename: Razelle
authors.initials: R
authors.lastname: Kurzrock
authors.forename: Robert C
authors.initials: RC
authors.lastname: Bast
authors.forename: Gordon B
authors.initials: GB
authors.lastname: Mills
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000077216:Carcinoma, Ovarian Epithelial; D018572:Disease-Free Survival; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D008875:Middle Aged; D060787:Neoplasm Grading; D009375:Neoplasms, Glandular and Epithelial / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D009944:Organoplatinum Compounds / Q000494:pharmacology; D010051:Ovarian Neoplasms / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D010767:Phosphorylcholine / Q000008:administration & dosage / Q000031:analogs & derivatives; D049268:Positron-Emission Tomography; D011446:Prospective Studies; D019275:Radiopharmaceuticals; D043823:Taxoids / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D009944:Organoplatinum Compounds; D019275:Radiopharmaceuticals; D043823:Taxoids; D019788:Fluorodeoxyglucose F18; D010767:Phosphorylcholine; D000077143:Docetaxel; C105905:perifosine