Pilot study evaluating the pharmacokinetics, pharmacodynamics, and safety of the combination of exemestane and tamoxifen.
OBJECTIVE
We conducted a pilot study assessing the effects of the selective estrogen receptor modulator, tamoxifen, on the pharmacokinetics, pharmacodynamics, and safety of the steroidal, irreversible aromatase inhibitor (AI), exemestane, when the two were coadministered in postmenopausal women with metastatic breast cancer.


METHODS
Patients with documented or unknown hormone receptor sensitivity were eligible. Patients received oral exemestane at 25-mg once daily. Starting day 15, oral tamoxifen at 20-mg once daily, was added. We measured plasma concentrations of exemestane, estrone, estrone sulfate, and estradiol after 14 days of exemestane monotherapy and after approximately 4 weeks of combination therapy. The incidence and severity of adverse events were assessed by physical examination and patient reporting.


RESULTS
We treated 18 patients. All had received prior chemotherapy and/or hormonal therapy, eight and six, respectively, with single-agent selective estrogen receptor modulators or irreversible aromatase inhibitors; no hormonal therapy was given within 30 days of study entry. Plasma exemestane concentrations and estrone, estrone sulfate, and estradiol suppression were unchanged after approximately 4 weeks of tamoxifen coadministration. All drug-related adverse events were grades 1 or 2; none was unexpected. Although not a formal study end point, antitumor activity was noted, with two partial responses and four cases of stable disease among 17 evaluable patients after a 9-month median follow-up (range, 2.5-19 months).


CONCLUSIONS
This pilot study provides evidence that coadministration of tamoxifen does not affect exemestane pharmacokinetics or pharmacodynamics and that the combination is well-tolerated and active. Further clinical investigation is warranted.
Rivera
Edgardo
E
Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030-4009, USA. erivera@mdanderson.org
Valero
Vicente
V
Francis
Deborah
D
Asnis
Aviva G
AG
Schaaf
Larry J
LJ
Duncan
Barbara
B
Hortobagyi
Gabriel N
GN
D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D000730:Androstadienes / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004958:Estradiol / Q000097:blood; D004970:Estrone / Q000031:analogs & derivatives* / Q000097:blood; D005260:Female; D049671:History, 18th Century; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D010865:Pilot Projects; D013629:Tamoxifen / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology
D000730:Androstadienes; D013629:Tamoxifen; D004970:Estrone; D004958:Estradiol; C056516:exemestane; C017296:estrone sulfate