Aromatase inhibition with 4-hydroxyandrostenedione in the treatment of postmenopausal patients with advanced breast cancer: a phase II study.
Estrogen deprivation by aromatase inhibition is an effective treatment in breast cancer. Between October 1986 and March 1988, 91 postmenopausal patients with advanced breast cancer entered a phase II study performed jointly in three center to investigate the new aromatase inhibitor 4-hydroxyandrostenedione. Patients received 500 mg 4-hydroxyandrostenedione intramuscularly (IM) every 2 weeks for 6 weeks, and 250 mg every 2 weeks thereafter. There were two complete (CRs) and 19 partial remissions (PRs) (response rate, 23%). Disease stabilization (no change; NC) was seen in 26 patients, and in 44 patients (48%), disease progression occurred. Duration of the CRs is 20+ months, median durations of PR and NC are 13+ and 8 months, respectively. Receptor status, relapse-free interval, and sites of metastatic lesions did not appear to influence treatment results. However, efficacy of previous tamoxifen treatment favorably predicted response to 4-hydroxyandrostenedione. Serum estradiol levels decreased significantly in patients after 2 weeks of treatment. Side effects were mostly nonspecific and of low degree, requiring discontinuation of treatment in only 3% of the patients. We conclude that aromatase inhibition with 4-hydroxyandrostenedione is efficacious in the treatment of postmenopausal breast cancer.
Department of Internal Medicine (Cancer Research), University of Essen Medical School, Federal Republic of Germany.
K
K
Höffken
W
W
Jonat
K
K
Possinger
M
M
Kölbel
T
T
Kunz
H
H
Wagner
R
R
Becher
R
R
Callies
P
P
Friederich
W
W
Willmanns
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000735:Androstenedione / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D047072:Aromatase Inhibitors; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D004341:Drug Evaluation; D004958:Estradiol / Q000097:blood; D005260:Female; D005860:Germany, West; D006801:Humans; D015993:Life Tables; D008593:Menopause; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D011960:Receptors, Estrogen / Q000378:metabolism; D012074:Remission Induction; D013629:Tamoxifen / Q000627:therapeutic use
D000970:Antineoplastic Agents; D047072:Aromatase Inhibitors; D011960:Receptors, Estrogen; D013629:Tamoxifen; D000735:Androstenedione; D004958:Estradiol; C014594:formestane