Jordan V C
Robert H. Lurie Cancer Center, Northwestern University Medical School, Chicago, Illinois 60611, USA.
Annu Rev Pharmacol Toxicol. 1995;35:195-211. doi: 10.1146/annurev.pa.35.040195.001211.
Tamoxifen, a nonsteroidal antiestrogen, is the endocrine therapy of choice for all stages of breast cancer. There are six million women-years of experience with tamoxifen, and the drug has produced survival advantages in node-positive and node-negative patients who have had 2-5 years of adjuvant tamoxifen therapy. A low incidence of side effects has been reported with tamoxifen, resulting in the proposal to use the antiestrogen as a preventive agent for breast cancer. Three separate clinical trials are currently under way--in the United States, Italy, and the United Kingdom. Current concerns about tamoxifen are the development of rat liver tumors during long-term treatment and an increased incidence of endometrial carcinomas observed in patients. Another concern is the development of drug resistance to long-term tamoxifen therapy. There is increased interest in both determining the mechanism of drug resistance and evaluating new antiestrogens that may be more beneficial as a preventive, as an adjuvant therapy, or for the treatment of advanced breast cancer.
他莫昔芬是一种非甾体类抗雌激素药物，是乳腺癌各阶段内分泌治疗的首选药物。他莫昔芬已有600万妇女年的使用经验，对于接受了2至5年辅助性他莫昔芬治疗的淋巴结阳性和淋巴结阴性患者，该药物都具有生存优势。据报道，他莫昔芬的副作用发生率较低，因此有人提议将这种抗雌激素药物用作乳腺癌的预防剂。目前美国、意大利和英国正在进行三项独立的临床试验。目前对他莫昔芬的担忧包括长期治疗期间大鼠肝脏肿瘤的发生以及患者子宫内膜癌发病率的增加。另一个担忧是长期他莫昔芬治疗会产生耐药性。人们对确定耐药机制以及评估可能作为预防剂、辅助治疗药物或用于治疗晚期乳腺癌更有益的新型抗雌激素药物的兴趣日益浓厚。
