title: Phase II trial of exemestane in combination with fulvestrant in postmenopausal women with advanced, hormone-responsive breast cancer.
abstract: BACKGROUND
  Exemestane, the irreversible steroidal aromatase inhibitor, and fulvestrant, the pure estrogen antagonist, are active as single drugs in postmenopausal women with advanced hormone-responsive breast cancer. We designed a phase II study with the purpose of determining whether combining these 2 drugs with different and potentially complementary mechanisms of action will improve the clinical benefit.
  
  
  METHODS
  Forty postmenopausal women with hormone-responsive advanced breast cancer received intramuscular injection of fulvestrant 250 mg every 28 days in combination with daily exemestane 25 mg until disease progression. We examined the influence of fulvestrant on exemestane pharmacokinetics and the effect of exemestane and fulvestrant on serum IGF-1 (insulin-like growth factor 1) and IGFBP-3 (IGF-binding protein 3) levels.
  
  
  RESULTS
  The observed proportion of patients free of progressive disease at 6 months after the initiation of treatment with exemestane and fulvestrant was 50%, a rate similar to that achieved with single-agent exemestane or fulvestrant in the first- or second-line setting. Pharmacokinetics parameters showed that coadministration of fulvestrant did not result in clinically relevant changes in exemestane plasma concentrations. A comparison of IGF-1 and IGFBP-3 levels demonstrated the increase of 35% and 12%, respectively, in mean levels from baseline to day 120.
  
  
  CONCLUSIONS
  The combination of exemestane and fulvestrant did not improve clinical benefit. The observed lack of improved efficacy was not related to altered drug exposure.
authors.affiliation: Division of Medical Oncology, The Ohio State University Medical Center, Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Columbus, OH 43210, USA. ewa.mrozek@osumc.edu
authors.forename: Ewa
authors.initials: E
authors.lastname: Mrózek
authors.forename: Rachel
authors.initials: R
authors.lastname: Layman
authors.forename: Bhuvaneswari
authors.initials: B
authors.lastname: Ramaswamy
authors.forename: Larry
authors.initials: L
authors.lastname: Schaaf
authors.forename: Xiaobai
authors.initials: X
authors.lastname: Li
authors.forename: Susan
authors.initials: S
authors.lastname: Ottman
authors.forename: Charles L
authors.initials: CL
authors.lastname: Shapiro
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000730:Androstadienes / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D004958:Estradiol / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D005260:Female; D000077267:Fulvestrant; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008875:Middle Aged; D017698:Postmenopause; D011960:Receptors, Estrogen / Q000096:biosynthesis; D011980:Receptors, Progesterone / Q000096:biosynthesis
chemical_list: D000730:Androstadienes; D018972:Insulin-Like Growth Factor Binding Protein 3; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D000077267:Fulvestrant; D004958:Estradiol; D007334:Insulin-Like Growth Factor I; C056516:exemestane