Endocrine effects of tamoxifen plus exemestane in postmenopausal women with breast cancer.
OBJECTIVE
In some specific circumstances, combined hormonal therapies for breast cancer seem to be more effective than single maneuvers. In two laboratory mammary cancer models, the combination of the aromatase inactivator exemestane plus tamoxifen gives a higher response rate than is found with either agent alone. To evaluate the endocrine effects of the combination of exemestane and tamoxifen, we studied 33 postmenopausal women disease-free following primary treatments for breast cancer who were taking tamoxifen for at least 3 months.


METHODS
After observation for symptoms on tamoxifen for 4 weeks, blood samples were taken and patients were begun additionally on exemestane 25 mg p.o. qd. Eight weeks later, blood samples were again taken, and exemestane was discontinued.


RESULTS
A decrease in alkaline phosphatase was found with exemestane treatment (P = 0.06), whereas no change in osteocalcin level was observed. A decrease in high-density lipoprotein cholesterol level was found (P = 0.0025), whereas total cholesterol, low-density lipoprotein cholesterol and triglyceride levels showed no changes with exemestane treatment. Estradiol, estrone, and estrone sulfate levels decreased to immeasurable or very low levels with exemestane treatment (all P < 0.001). No significant changes in frequencies of common drug-associated side effects, such as vasomotor symptoms or weight change, were found.


CONCLUSIONS
Based on the absence of adverse endocrine effects with the addition of exemestane to tamoxifen therapy observed in this study, further clinical evaluation of the efficacy of this combination is warranted.
Love
Richard R
RR
Department of Medicine, University of Wisconsin, 610 Walnut Street, 256 Warf Office Building, Madison, WI 53726, USA. rrlove@facstaff.wisc.edu
Hutson
Paul R
PR
Havighurst
Thomas C
TC
Cleary
James F
JF
D000328:Adult; D000368:Aged; D000469:Alkaline Phosphatase / Q000097:blood; D000730:Androstadienes / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D047072:Aromatase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy*; D008076:Cholesterol, HDL / Q000097:blood; D004958:Estradiol / Q000097:blood; D004965:Estrogen Antagonists / Q000008:administration & dosage / Q000009:adverse effects; D004970:Estrone / Q000031:analogs & derivatives* / Q000097:blood; D005076:Exanthema / Q000139:chemically induced; D005260:Female; D019584:Hot Flashes / Q000139:chemically induced; D006801:Humans; D008875:Middle Aged; D017698:Postmenopause; D013629:Tamoxifen / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome
D000730:Androstadienes; D047072:Aromatase Inhibitors; D008076:Cholesterol, HDL; D004965:Estrogen Antagonists; D013629:Tamoxifen; D004970:Estrone; D004958:Estradiol; D000469:Alkaline Phosphatase; C056516:exemestane; C017296:estrone sulfate