Sequential tamoxifen and aminoglutethimide versus tamoxifen alone in the adjuvant treatment of postmenopausal breast cancer patients: results of an Italian cooperative study.
OBJECTIVE
To determine whether switching patients from tamoxifen to antiaromatase treatment would prevent some of the relapses or deaths that we assume would occur if tamoxifen were continued.


METHODS
Three hundred eighty postmenopausal breast cancer patients receiving adjuvant tamoxifen treatment for 3 years were randomized to either continue tamoxifen for 2 more years or to switch to low-dose aminoglutethimide (250 mg daily) for 2 years.


RESULTS
At a median follow-up of 61 months (range, 5 to 94 months), 59 events occurred in the tamoxifen group, and 55 occurred in the aminoglutethimide group. More treatment failures at distant sites, such as viscera (P =.02), were observed in the tamoxifen group. Although no differences in disease-free survival between the two groups have emerged so far, a significant trend favors aminoglutethimide in overall survival (P =.005) and breast cancer-specific survival (P =.06). Even if more patients in the antiaromatase group complained of drug-related side effects and more of them discontinued treatment (P =.0001), the number of cardiovascular events and, in general, of life-threatening adverse events was higher in the tamoxifen arm.


CONCLUSIONS
Switching patients from tamoxifen to aminoglutethimide treatment resulted in comparable event-free survival, but longer overall survival was achieved in patients who were switched to aminoglutethimide as compared with those who continued to receive tamoxifen. Should these preliminary results be confirmed by larger studies with a similar design, which are now testing the effectiveness of the new, more active, and tolerable aromatase inhibitors, sequencing tamoxifen with an aromatase inhibitor could become a preferable alternative to tamoxifen alone in early breast cancer patients.
Boccardo
F
F
Professorial Unit of Medical Oncology, University and National Cancer Research Institute, Largo R Benzi 10, 16132 Genoa, Italy. boccardo@hp380.ist.unige.it
Rubagotti
A
A
Amoroso
D
D
Mesiti
M
M
Romeo
D
D
Caroti
C
C
Farris
A
A
Cruciani
G
G
Villa
E
E
Schieppati
G
G
Mustacchi
G
G
D000368:Aged; D000616:Aminoglutethimide / Q000627:therapeutic use*; D047072:Aromatase Inhibitors; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D018572:Disease-Free Survival; D004351:Drug Resistance; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D004965:Estrogen Antagonists / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007558:Italy; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D017698:Postmenopause; D011960:Receptors, Estrogen / Q000378:metabolism; D015996:Survival Rate; D013629:Tamoxifen / Q000627:therapeutic use*
D047072:Aromatase Inhibitors; D004791:Enzyme Inhibitors; D004965:Estrogen Antagonists; D011960:Receptors, Estrogen; D013629:Tamoxifen; D000616:Aminoglutethimide