TOREMIFENE COMBINED WITH CYTOSTATICS - EFFECTS ON GROWTH AND HISTAMINE CONCENTRATION OF HUMAN MAMMARY-CANCER IN MOUSE SUBRENAL CAPSULE ASSAY (SRCA)

Antiestrogens have been demonstrated to reduce multidrug resistance (M DR) in vitro. Clinical trials with the antiestrogen toremifene (T) com bined with cytostatics are under way. We performed the 6-day subrenal capsule assay (SRCA) to 10 human mammary tumors to find out if T augme nts the potency of cytostatics in this model. The cancer tissue histam ine concentrations were measured to see if histamine plays a role in t he modulation. Toremifene and epirubicin (E) alone were not effective but together they caused significant reduction in tumor size (p < 0.00 01). 5-fluorouracil (5-FU) and cyclophosphamide were effective alone o r with T, whereas neither mitomycin (MMC) nor MMC + T were effective. Tissue histamine concentrations varied in individual tumors. The highe st values were in the T + E group (485 +/- 182 pmol/mg prot) which sig nificantly (p < 0.009) differed from the controls (245 +/- 155). There was an overall significant negative correlation (p < 0.01) between tu mor growth and histamine concentration. Treatment with T did not expla in the differences in histamine concentrations.