title: Multicenter, phase II trial of exemestane as third-line hormonal therapy of postmenopausal women with metastatic breast cancer. Aromasin Study Group.
abstract: OBJECTIVE
  To assess the antitumor activity, safety, and hormone-suppressive effects of the irreversible aromatase inactivator, exemestane (Aromasin, Pharmacia & Upjohn, Kalamazoo, MI), administered as third-line hormone therapy to postmenopausal women with metastatic breast cancer that is refractory to tamoxifen and megestrol acetate.
  
  
  METHODS
  Exemestane was administered at a dose of 25 mg/d orally until patients experienced disease progression. The efficacy and safety of exemestane were clinically and radiographically evaluated. The impact of exemestane treatment on tumor-related signs and symptoms was assessed. The effect of exemestane on serum levels of estrogens and other steroidal hormones was determined.
  
  
  RESULTS
  Ninety-one patients were treated. There were four complete responses (CR) and eight partial responses (PR), for an objective response rate of 13% in the entire treated population. The overall success rate (CR, PR, or stable disease [SD] >/= 24 weeks) was 30%. The median duration of response and overall success was 9 months and 8 months, respectively. Most patients with CR/PR (83%; 10 of 12 patients) and SD >/= 24 weeks (80%; 12 of 15 patients) had improved or stable tumor-related signs and symptoms. Mean levels of circulating estrone (E(1)), estradiol (E(2)), and estrone sulfate decreased to 11%, 22%, and 13% of baseline levels, respectively (at week 8 or 16 of treatment). One half of the patients had undetectable E(1) and E(2) levels during treatment, including at the time of disease progression. Mild nausea (20% of patients) and hot flashes (20%) were the most common drug-related adverse events and were generally grade 1.
  
  
  CONCLUSIONS
  Exemestane is an active and well-tolerated third-line hormonal therapy that represents a new treatment option for postmenopausal patients with advanced breast cancer that has become refractory to standard first- and second-line hormonal therapies.
authors.affiliation: U.S. Oncology Research at Baylor-Sammons Cancer Center, Dallas, TX, USA.
authors.forename: S
authors.initials: S
authors.lastname: Jones
authors.forename: C
authors.initials: C
authors.lastname: Vogel
authors.forename: A
authors.initials: A
authors.lastname: Arkhipov
authors.forename: L
authors.initials: L
authors.lastname: Fehrenbacher
authors.forename: P
authors.initials: P
authors.lastname: Eisenberg
authors.forename: B
authors.initials: B
authors.lastname: Cooper
authors.forename: S
authors.initials: S
authors.lastname: Honig
authors.forename: A
authors.initials: A
authors.lastname: Polli
authors.forename: F
authors.initials: F
authors.lastname: Whaley
authors.forename: E
authors.initials: E
authors.lastname: di Salle
authors.forename: J
authors.initials: J
authors.lastname: Tiffany
authors.forename: A
authors.initials: A
authors.lastname: Consonni
authors.forename: L
authors.initials: L
authors.lastname: Miller
mesh_terms: D000328:Adult; D000368:Aged; D000730:Androstadienes / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000556:secondary*; D017024:Chemotherapy, Adjuvant; D004967:Estrogens / Q000097:blood; D005260:Female; D006801:Humans; D008875:Middle Aged; D017698:Postmenopause
chemical_list: D000730:Androstadienes; D000970:Antineoplastic Agents; D004967:Estrogens; C056516:exemestane