Superior efficacy of letrozole versus tamoxifen as first-line therapy for postmenopausal women with advanced breast cancer: results of a phase III study of the international letrozole breast cancer group

To compare the efficacy and tolerability with that of letrozole, an oral aromatase inhibitior, with tomoxifen as first-line therapy in postmenopausal women with advanced breast cancer. Nine hundred seven patients were randomly assigned tetrolzole 2.5 mg once daily [453 patients] or tamoxifen 20 mg once daily [454 patients]. Patients had estrogen receptor- and/or progesterone receptor-positive tumor, or both receptors were unknown. Recurrence during adjuvant antiestrogen therapy or within the following 12 months or prior endocrine therapy for advanced disease precluded enrollment. One prior chemotherapy regimen for metastatic disease was allowed. The primary end point was time to progression [TTP]. Secondary end points included overall objective response [ORR], its duration, rate and duration of clinicalbenefit, time to treatment failure [TTF], overall survival, and tolerability. TTP was significantly longer for letrozole than for tamoxifen [median, 41 v 26 weeks]. Treatment with letrozle reduced the risk of progression by 30% [hazards ratio, 0.70; 95% confidence interval, 0.60 to 0.82, P=.0001]. TTP was significantly longer for letrozole irrespective of dominant site of disease, receptor status, or prior adjuvant antiestrogen therapy. Similarly, TTF was significantly longer for letrozole [median, 40 v 25 weeks]. ORR was higher for letrozole [30% v 20%; P= .0006], as was the rate of clinical benefit [49% v 38%; P= .001]. Survival date are currently immature and not reported here. Both treatment were well tolerated. Letrozole was significantly superior to tamoxifen in TTP, TTF, ORR, and clinical benefit rate. Our results supports its use as first-line endocrine therapy in postmenopausal women with advanced breast cancer

Comparative study of aromatase inhibitor, letrozole, versus medroxy-progesterone acetate for the treatment of endometrial hyperlasia

This study included 40 women [35 to 40] years of age, all were complaining of irregular uterine bleeding. The women were randomized after counseling into two groups: Groups I [n=20] had given medroxy-progesterone acetate 5 mg twice daily and group II [n=20] had given 2.5 mg letrozole tablets twice daily. The duration needed for the stopping of bleeding, the need for further intervention or treatment were recorded. Moreover, after 3 and 6 months, both groups had another endometrial biopsy re-evaluated. The investigator was blind to the allocation as the drugs were dispersed by the hospital pharmacy in registered code. Medroxy-progesterone was found to be significantly more effective in controlling the uterine bleeding compared to letrozole [mean duration 8.3 in group I versus 12.1 days in group II]. However, letrozole was statistically insignificant in returning the normal endometrial pattern after 3 month treatment compared to medroxy-progesterone. On the other hand, letrozole was statistically significant in returning the normal endometrial pattern after 6 month treatment compared to medroxy-progesterone. Finally, the need for further intervention was less in the letrozole group

Study of the effect of letrozole in postmenopausal patients with advanced breast cancer resistant to tamoxifen

A study on 25 postmenopausal patients suffering from advanced breast cancer resistant to tamoxifen while on treatment or recurrence after its use was done by treating them with Letrozole for six months and in 15 patients by completing one year with Letrozole. Toxicity from Letrozole was minimum and easily manageable. In the first six months [in 25 patients] overall response was 28%, complete response 4% and partial response 24%. Disease was stable in 24% of cases so the overall clinical benefit was in 52%. At the end of one year of treatment [in 15 patients] the overall response was 20% with no complete response and 20% partial response. There was no change in 13% of patients so collectively clinical benefit was in 33% of cases. There was no benefit in those who had disease progression within 6 months of treatment and then by continuing the drug for further period. Those with partial response and no change at 6 months clearly benefited by continuing the drug further

Cinética de la respuesta esteroidogénica a la estimulación testicular con gonadotrofina coriónica: aplicación clínica en hombres con infertilidad asintomática / Kinetics the steroidogenic response to the testicular stimulation whit gonadotrophin chorionic: clinical application in asymptomatic infertile man

En el presente trabajo, hemos desarrollado una prueba de estimulación testicular simplificada y de aplicación clínica. Además, se correlacionó la respuesta esteroidogénica a la hCG, con las alteraciones espermatogénicas en hombres con infertilidad asintomática. Los niveles circulantes de testosterona (T), estradiol (E2), 17OH-Progesterona (17OHP) fueron determinados en condiciones basales (3 muestras de sangre tomadas en intervalos de 15 min) y a las 2, 4, 24 y 48 h después de la inyección i.m. de 5.000 UI de hCG, en 420 pacientes oligoastenospérmicos normoprolactinémicos con niveles normales de LH y FSH. Las respuestas de T y 17OHP a la hCG, en el grupo control, mostraron un patrón bifásico con un pico agudo a las 4 h y un pico más sostenido y retrasado luego de las 24 h. Los pacientes infértiles mostraron 2 tipos de respuesta de la T a la hCG: grupo 1) (n = 290), con una respuesta disminuida entre las 2 y 4 h, pero en el rango de los valores de los hombres normales entre las 24 y las 48 h, y un grupo 2 (n = 130) con una respuesta de T similar al grupo control. Las respuestas de E2 en los pacientes del grupo 1 y 2 fueron similares a las del grupo control. La hCG indujo un crecimiento significativo en la relación 170HP/T en los pacientes del grupo 1. En 22 pacientes: 16 del grupo 1 y 6 del grupo 2, se administró aminoglutetimida-hidrocortisana (AGT-HC), un inhibidor de la aromatasa, durante 90 días. Díez pacientes del grupo 1 normalizaron el espermograma (5 de los cuales lograron embarazos, en 5 se obtuvo un incremento significativo de los espermatozoides grado 3 y en 1 no se observaron cambios. Por otro lado, sólo 1 paciente del grupo 2 presentó una leve mejoría en la calidad del semen. La AGT disminuyó la concentración de E2 y aumentó las gonadotrofinas y la relación T/E2. En los pacientes del grupo 1 se incrementó la respuesta aguda de T a la hCG, durante el tratamiento. Nuestros resultados sugieren que 1), el E2 podría estar involucrado, tanto en la etiología de algunos casos de oligoazoospermia, como en la falta de respuesta aguda de T a la hCG, induciendo, posiblemente, un bloqueo parcial de la 17,20 desmolasa; 2) la mejoría de la calidad del semen inducida por el AGT-HC podría estar relacionada a un incremento en la relación T:E2, a una disminución intratesticular de E2, a un incremento de gonadotrofinas o a la suma de cambios hormonales; 3) solamente los pacientes con una respuesta aguda disminuidas de T a la hCG serían posibles para el tratamiento