Multicenter, phase II trial of exemestane as third-line hormonal therapy of postmenopausal women with metastatic breast cancer. Aromasin Study Group.
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.
Jones
S
S
U.S. Oncology Research at Baylor-Sammons Cancer Center, Dallas, TX, USA.
Vogel
C
C
Arkhipov
A
A
Fehrenbacher
L
L
Eisenberg
P
P
Cooper
B
B
Honig
S
S
Polli
A
A
Whaley
F
F
di Salle
E
E
Tiffany
J
J
Consonni
A
A
Miller
L
L
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
D000730:Androstadienes; D000970:Antineoplastic Agents; D004967:Estrogens; C056516:exemestane