COMPARISON OF TOREMIFENE AND TAMOXIFEN IN POSTMENOPAUSAL PATIENTS WITH ADVANCED BREAST-CANCER - A RANDOMIZED DOUBLE-BLIND, THE NORDIC PHASE-III STUDY

The study was planned to compare, in a prospective double-blind random ized 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)-positiv e or ER-unknown advanced breast cancer were randomly assigned to recei ve daily either 60 mg TOR or 40 mg TAM. The patients were stratified t o measurable and non-measurable but evaluable groups. They were assess ed for response to therapy, time to progression (TTP), time to treatme nt failure (TTF), response duration, overall survival and drug toxicit y. Two hundred and fourteen patients were randomized into TOR and 201 into TAM treatment. The response rate (complete + partial) was 31.3% f or TOR and 37.3% for TAM (P = 0.215). The 95% confidence interval (CI) for the 6% difference was -15.1% to 3.1%. The median TTP was 7.3 mont hs for TOR and 10.2 months for TAM (P = 0.047). The 95% CI for the haz ard 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 rat io was 0.89 and the subsequent 95% CI 0.73-1.09. The median overall su rvival was 33.0 months for TOR and 38.7 months for TBM (P = 0.645). Th e hazard ratio was 0.94 with 95% CI of 0.73-1.22. The transient differ ence in TTP may be related to an imbalance in ER content of the tumour s. When only patients with ER-positive tumours were considered (n = 23 8), 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 d ue to these events (3.5% vs 0.9%). Treatment-emerged moderate dizzines s (P = 0.026) and cataracts (P = 0.026) were more frequent among TAM t han among TOR patients. In conclusion, TOR (60 mg day(-1)) and TAM (40 mg day(-1)) are equally effective and safe in the treatment of advanc ed post-menopausal ER-positive or ER-unknown breast cancer.