3. A randomized trial of exemestane after two to three years of tamoxifen therapy in postmenopausal women with primary breast cancer.
Tamoxifen, taken for five years, is the standard adjuvant treatment for postmenopausal women with primary, estrogen-receptor-positive breast cancer. Despite this treatment, however, some patients have a relapse. A double-blind, randomized trial was conducted to test whether, after two to three years of tamoxifen therapy, switching to exemestane was more effective than continuing tamoxifen therapy for the remainder of the five years of treatment. The primary end point was disease-free survival. Of the 4742 patients enrolled, 2362 were randomly assigned to switch to exemestane, and 2380 to continue to receive tamoxifen. After a median follow-up of 30.6 months, 449 first events (local or metastatic recurrence, contralateral breast cancer, or death) were reported--183 in the exemestane group and 266 in the tamoxifen group. The unadjusted hazard ratio in the exemestane group as compared with the tamoxifen group was 0.68 (95 percent confidence interval, 0.56 to 0.82; P<0.001 by the log-rank test), representing a 32 percent reduction in risk and corresponding to an absolute benefit in terms of disease-free survival of 4.7 percent (95 percent confidence interval, 2.6 to 6.8) at three years after randomization. Overall survival was not significantly different in the two groups, with 93 deaths occurring in the exemestane group and 106 in the tamoxifen group. Severe toxic effects of exemestane were rare. Contralateral breast cancer occurred in 20 patients in the tamoxifen group and 9 in the exemestane group (P=0.04). It is concluded that Exemestane therapy after two to three years of tamoxifen therapy significantly improved disease-free survival as compared with the standard five years of tamoxifen treatment.
Coombes RC, Hall E, Gibson LJ, Paridaens R, Jassem J, Delozier T, Jones SE, Alvarez I, Bertelli G, Ortmann O, Coates AS, Bajetta E, Dodwell D, Coleman RE, Fallowfield LJ, Mickiewicz E, Andersen J, Lonning PE, Cocconi G, Stewart A, Stuart N, Snowdon CF, Carpentieri M, Massimini G, Bliss JM; Intergroup Exemestane Study. A randomized trial of exemestane after two to three years of tamoxifen therapy in postmenopausal women with primary breast cancer. N Engl J Med. 2004 Mar 11;350(11):1081-92.
Piccart-Gebhart MJ New stars in the sky of treatment for early breast cancer. N Engl J Med. 2004 Mar 11;350(11):1140-2. No abstract available.
4. Luteolysis induced by a gonadotropin-releasing hormone agonist is the key to prevention of ovarian hyperstimulation syndrome.
In this paper the available knowledge on the use of GnRH agonist for ovulation triggering as a means to prevent ovarian hyperstimulation syndrome (OHSS) is reviewed. Therefore, a review of pertinent English language studies published over the past 15 years was performed.. The available literature suggests that while GnRH agonist effectively induces final oocyte maturation and ovulation, it also completely and reliably prevents clinically significant OHSS. The mechanism of action in the context of OHSS prevention involves complete, quick, and irreversible luteolysis. Controlled ovarian stimulation protocols based on GnRH antagonist to prevent premature LH rise and GnRH agonist for ovulation triggering provide a safe and OHSS-free clinical environment. Adequate luteal support compensates for luteolysis and assures good clinical outcome. The fertility community is urged to adopt these protocols. This will make OHSS a disease of the past.
Kol S. Luteolysis induced by a gonadotropin-releasing hormone agonist is the key to prevention of ovarian hyperstimulation syndrome. Fertil Steril. 2004 Jan;81(1):1-5.