title: Randomized, double-blind, multicenter trial comparing two doses of arzoxifene (LY353381) in hormone-sensitive advanced or metastatic breast cancer patients.
abstract: BACKGROUND
  This randomized, double-blind, phase II study assessed two doses of the selective estrogen receptor modulator arzoxifene in women with advanced breast cancer. The primary end point was to choose the best of two doses of arzoxifene based on the response rate or the clinical benefit rate (CBR). Pharmacokinetics and toxicities were also assessed.
  
  
  METHODS
  Ninety-two patients with advanced breast cancer received arzoxifene 20 or 50 mg/day. Tumor response was assessed using World Health Organization criteria. Toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI-CTC) system. Pharmacokinetic data were analyzed using the NONMEM software program (GloboMax, Hanover, MD, USA).
  
  
  RESULTS
  Response rates in the 20 mg arm were numerically higher than the 50-mg arm according to the investigator (40.5% versus 36.4%) and the independent review panel (42.9% versus 27.3%). CBR was higher in the 20 mg arm according to the investigator (64.3% versus 61.4%) and the independent review panel (59.5% versus 47.7%). Arzoxifene was well tolerated. There were no study drug-related deaths. Mean observed steady-state plasma concentrations of arzoxifene were 3.62 and 7.48 ng/ml for the 20 and 50 mg doses, respectively.
  
  
  CONCLUSIONS
  There were no significant differences in efficacy or safety between 20 and 50 mg of arzoxifene. Accordingly, arzoxifene 20 mg/day was selected for further study in patients with breast cancer.
authors.affiliation: Vall D'Hebron University Hospital, Barcelona, Spian. jbaselga@vhebron.net
authors.forename: J
authors.initials: J
authors.lastname: Baselga
authors.forename: A
authors.initials: A
authors.lastname: Llombart-Cussac
authors.forename: M
authors.initials: M
authors.lastname: Bellet
authors.forename: V
authors.initials: V
authors.lastname: Guillem-Porta
authors.forename: N
authors.initials: N
authors.lastname: Enas
authors.forename: K
authors.initials: K
authors.lastname: Krejcy
authors.forename: E
authors.initials: E
authors.lastname: Carrasco
authors.forename: L
authors.initials: L
authors.lastname: Kayitalire
authors.forename: M
authors.initials: M
authors.lastname: Kuta
authors.forename: A
authors.initials: A
authors.lastname: Lluch
authors.forename: P
authors.initials: P
authors.lastname: Vodvarka
authors.forename: P
authors.initials: P
authors.lastname: Kerbrat
authors.forename: M
authors.initials: M
authors.lastname: Namer
authors.forename: L
authors.initials: L
authors.lastname: Petruzelka
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy*; D017024:Chemotherapy, Adjuvant; D004305:Dose-Response Relationship, Drug; D004717:Endometrium / Q000187:drug effects; D005260:Female; D006801:Humans; D008875:Middle Aged; D010880:Piperidines / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D020845:Selective Estrogen Receptor Modulators / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D013876:Thiophenes / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D018931:Antineoplastic Agents, Hormonal; D010880:Piperidines; D020845:Selective Estrogen Receptor Modulators; D013876:Thiophenes; C115121:LY 353381