The activity, toxicity, and side effects of TOR in postmenopausal women with hormone receptor-positive or -unknown metastatic breast cancer are similar if not equivalent to those of TAM. We detected no clear evidence of a dose-response effect for TOR. TOR60 is an effective and safe agent for the treatment of postmenopausal women with hormone receptor-positive metastatic breast cancer and can be considered an alternative to TAM as first-line treatment for such patients.

We conclude that changes in bone scintigraphy that mimic progressive disease early in the course of hormonal treatment of patients with breast cancer metastatic to bone may represent scintigraphic flare associated with response. Thus, clinicians must be cognizant of the phenomenon of scintigraphic flare to avoid premature discontinuation of a potentially beneficial treatment.

We conclude that there is major cross-resistance between tamoxifen and toremifene and that only occasional tamoxifen-refractory patients will have objective responses to toremifene.

A multicenter phase I pharmacokinetic study of a new triphenylethylene antiestrogen, toremifene, was examined in 70 patients with advanced breast cancer. Patients were randomized to receive single daily oral doses of either 10, 20, 40, 60, 200, or 400 mg for 8 weeks. Plasma toremifene and its major metabolites. N-desmethyltoremifene and 4-hydroxytoremifene, were determined weekly during therapy and at 0, 7, 14, and 21 days after the discontinuation of therapy. The time to reach steady-state plasma concentrations was between 1 and 5 weeks, with steady-state being achieved earlier (1-2 weeks) at daily doses of 200 and 400 mg. The time to peak concentration following oral doses of toremifene ranged from 1.5 to 4.5 h. The terminal half-life of elimination was 5.0, 6.0, and 5.0 days for toremifene, desmethyltoremifene, and 4-hydroxytoremifene, respectively. Plasma concentrations of 4-hydroxytoremifene were detectable only at high doses (200 and 400 mg/day) of toremifene. The results of this phase I pharmacokinetic study show that toremifene has metabolic and kinetic patterns that are similar to those previously reported with tamoxifen.

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