RESUMEN
PURPOSE: To determine the efficacy and safety of EM-800 (SCH-57050), the precursor of acolbifene, a new, highly potent, orally active, pure antiestrogen in the mammary gland and endometrium, for the treatment of tamoxifen-resistant breast cancer. PATIENTS AND METHODS: Forty-three post menopausal/ovariectomized women with breast cancer who had received tamoxifen, either for metastatic disease or as adjuvant to surgery for > or = 1 year, and had relapsed were treated in a prospective, multicenter, phase II study with EM-800 (20 mg/d [n = 21] or 40 mg/d [n = 22] orally). Results Thirty-seven patients had estrogen receptor (ER)-positive tumors (>10 fmol/mg; mean, 146 fmol/mg cytosolic protein), three patients had ER-negative/progesterone receptor-positive tumors, and three patients had undetermined ER status. The objective response rate to EM-800 was 12%, with one complete response and four partial responses. Ten patients (23%) had stable disease for > or = 3 months, and 7 patients (16%) had stable disease for > or = 6 months. With a median follow-up of 29 months, median duration of response was 8 months (range, 7 to 71+ months). Treatment with EM-800 was well tolerated. No significant adverse events related to the study drug were observed clinically or biochemically. CONCLUSION: EM-800 produced responses in a significant proportion of patients with tamoxifen-resistant breast cancer, thus showing that this highly potent, selective estrogen receptor modulator, which lacks estrogenic activity in the mammary gland and endometrium, has incomplete cross-resistance with tamoxifen, thus suggesting additional benefits in the treatment of breast cancer.
Asunto(s)
Benzopiranos/administración & dosificación , Neoplasias de la Mama/tratamiento farmacológico , Carcinoma/tratamiento farmacológico , Carcinoma/secundario , Resistencia a Antineoplásicos , Antagonistas de Estrógenos/administración & dosificación , Dosis Máxima Tolerada , Propionatos/administración & dosificación , Administración Oral , Adulto , Anciano , Anciano de 80 o más Años , Benzopiranos/farmacocinética , Disponibilidad Biológica , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Antagonistas de Estrógenos/farmacocinética , Femenino , Humanos , Metástasis Linfática , Persona de Mediana Edad , Estadificación de Neoplasias , Profármacos , Propionatos/farmacocinética , Estudios Prospectivos , Medición de Riesgo , Análisis de Supervivencia , Tamoxifeno/administración & dosificación , Resultado del TratamientoRESUMEN
PURPOSE: This clinical trial is aimed at evaluating the impact of prostate cancer screening on cancer-specific mortality. SUBJECTS AND METHODS: Forty-six thousand four hundred and eighty-six (46,486) men aged 45-80 years registered in the electoral roll of the Quebec city area were randomized in 1988 between screening and no screening. Screening included measurement of serum prostatic specific antigen (PSA) using 3.0 ng/ml as upper limit of normal and digital rectal examination (DRE) at first visit. At follow-up visits, serum PSA only was used. RESULTS: Seventy-four (74) deaths from prostate cancer occurred in the 14,231 unscreened controls while 10 deaths were observed in the screened group of 7,348 men during the first 11 years following randomization. Median follow-up of screened men was 7.93 years. A Cox proportional hazards model of the age at death from prostate cancer shows a 62% reduction (P < 0.002, Fisher's exact test) of cause-specific mortality in the screened men (P = 0.005). These results are in agreement with the continuous decrease of prostate cancer mortality observed in North America.