Inhibitory effect of combined treatment with the aromatase inhibitor exemestane and tamoxifen on DMBA-induced mammary tumors in rats

J Steroid Biochem Mol Biol. 1993 Mar;44(4-6):677-80. doi: 10.1016/0960-0760(93)90280-a.

Abstract

The antitumor effect of exemestane (FCE 24304), an irreversible aromatase inhibitor, given alone or in combination with tamoxifen, was investigated in rats with 7,12-dimethylbenzanthracene (DMBA)-induced mammary tumors. The compounds were given once daily, 6 days a week for 4 weeks. Exemestane, given at the dose of 20 mg/kg/day s.c., induced 26% complete (CR) and 18% partial (PR) tumor regressions, compared to 0% CR and 6% PR observed in controls. Tamoxifen, given at 1 mg/kg/day p.o., induced 16% CR and 13% PR. The combined treatment caused 41% CR and 16% PR, thus resulting in a higher antitumor effect than either single treatment. The appearance of new tumors was reduced by each single treatment and almost totally prevented by the combined treatment. Serum prolactin (PRL) levels, assayed 4 h after the last dose, were unchanged in the group treated with the combination, whereas tamoxifen alone caused a slight increase of serum PRL. These results indicate that estrogen deprivation through aromatase inhibition and estrogen receptor antagonism causes a better inhibition of DMBA-induced mammary tumors than either treatment modality alone.

MeSH terms

  • 9,10-Dimethyl-1,2-benzanthracene
  • Adrenal Glands / anatomy & histology
  • Adrenal Glands / drug effects
  • Androstadienes / therapeutic use*
  • Animals
  • Antineoplastic Agents / therapeutic use*
  • Aromatase Inhibitors*
  • Drug Synergism
  • Female
  • Mammary Neoplasms, Experimental / chemically induced
  • Mammary Neoplasms, Experimental / drug therapy*
  • Organ Size / drug effects
  • Ovary / anatomy & histology
  • Ovary / drug effects
  • Pituitary Gland / anatomy & histology
  • Pituitary Gland / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Tamoxifen / therapeutic use*
  • Uterus / anatomy & histology
  • Uterus / drug effects

Substances

  • Androstadienes
  • Antineoplastic Agents
  • Aromatase Inhibitors
  • Tamoxifen
  • 9,10-Dimethyl-1,2-benzanthracene
  • exemestane