title: Pilot study evaluating the pharmacokinetics, pharmacodynamics, and safety of the combination of exemestane and tamoxifen.
abstract: 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.
authors.affiliation: Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030-4009, USA. erivera@mdanderson.org
authors.forename: Edgardo
authors.initials: E
authors.lastname: Rivera
authors.forename: Vicente
authors.initials: V
authors.lastname: Valero
authors.forename: Deborah
authors.initials: D
authors.lastname: Francis
authors.forename: Aviva G
authors.initials: AG
authors.lastname: Asnis
authors.forename: Larry J
authors.initials: LJ
authors.lastname: Schaaf
authors.forename: Barbara
authors.initials: B
authors.lastname: Duncan
authors.forename: Gabriel N
authors.initials: GN
authors.lastname: Hortobagyi
mesh_terms: 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
chemical_list: D000730:Androstadienes; D013629:Tamoxifen; D004970:Estrone; D004958:Estradiol; C056516:exemestane; C017296:estrone sulfate