SummaryThe study was planned to compare, in a prospective double-blind randomized trial, the efficacy and safety of toremifene (TOR) and tamoxifen (TAM) in post-menopausal patients with advanced breast cancer who have not had prior systemic therapy for advanced disease. Four hundred and fifteen post-menopausal patients with oestrogen receptor (ER)-positive or ER-unknown advanced breast cancer were randomly assigned to receive daily either 60 mg TOR or 40 mg TAM. The patients were stratified to measurable and non-measurable but evaluable groups. They were assessed for response to therapy, time to progression (TTP), time to treatment failure (TTF), response duration, overall survival and drug toxicity. Two hundred and fourteen patients were randomized into TOR and 201 into TAM treatment. The response rate (complete + partial) was 31.3% for TOR and 37.3% for TAM (P = 0.215). The 95% confidence interval (Cl) for the 6% difference was -15.1% to 3.1%. The median TTP was 7.3 months for TOR and 10.2 months for TAM (P = 0.047). The 95% Cl for the hazard ratio of 0.80 was 0.64-1.00. A percentage of the TOR patients (9.8%) and the TAM patients (18.9%) discontinued the treatment prematurely (P = 0.011) for various reasons. Consequently, the median TTF of 6.3 vs 8.5 months did not differ significantly (P = 0.271). The hazard ratio was 0.89 and the subsequent 95% Cl 0.73-1.09. The median overall survival was 33.0 months for TOR and 38.7 months for TAM (P = 0.645). The hazard ratio was 0.94 with 95% Cl of 0.73-1.22. The transient difference in TTP may be related to an imbalance in ER content of the tumours. When only patients with ER-positive tumours were considered (n = 238), no difference between two treatments was seen (P = 0.578). TAM was associated with an overall slightly higher frequency of adverse drug reactions than TOR (44.3 vs 39.3%) and a higher discontinuation rate due to these events (3.5% vs 0.9%). Treatment-emerged moderate dizziness (P = 0.026) and cataracts (P = 0.026) were more frequent among TAM than among TOR patients. In conclusion, TOR (60 mg day1) and TAM (40 mg day-1) are equally effective and safe in the treatment of advanced post-menopausal ER-positive or ER-unknown breast cancer.Keywords: antioestrogen; post-menopausal women; advanced breast cancer Tamoxifen (TAM) is the most common alternative for initial endocrine therapy of patients with recurrent or metastatic breast cancer. The overall response rate of post-menopausal women to TAM varies from 20% to 60% (Jaiyesimi et al, 1995). This wide range is largely due to the variability of prognostic factors in different study populations and to heterogeneous quality assessment. TAM, when given as an adjuvant treatment, is associated with a 20% mortality reduction (Santen et al, 1990; Early Breast Cancer Trialists' Collaborative Group, 1992).The presence of oestrogen receptors (ERs) in the breast cancer cells is the most important factor associated with successful treatment with TAM. Approximately 70% of al primary breast cancers
The effect of tamoxifen (TAM) on the serum levels of sexual hormones and on the sex hormone-binding globulin (SHBG) was investigated in 30 postmenopausal patients with advanced breast cancer. To study the ‘prolactin reserve capacity’ of the pituitary gland, thyrotrophin-releasing hormone (TRH) and sulpiride-induced prolactin release were measured prior to TAM treatment, then in the 2nd and 8th week of the therapy. The TRH (400 μg i.v.)-induced prolactin secretion was significantly suppressed by TAM after an 8-week treatment, but only in responding cases. Maximal prolactin stimulation occurred at the 15th min after TRH injection, being equal to 5,600 ± 800 mlU/l in cancer patients, and decreasing to 2,400 ± 150 mlU/l after 8 weeks. TAM did not suppress the sulpiride-inducable prolactin release either in responders or in nonrespon-ders.
According to the LHRH test, the antagonistic effect of toremifene seems to be more dominant than the concomitantly existing agonistic property. Neither clinical nor endocrinological side effects could be observed at the level of the CNS during a prolonged period of toremifene administration.
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