作者：Alison Palkhivala
出處：WebMD醫學新聞
September 17, 2008 (蒙特婁魁北克)－根據發表於美國骨骼與礦物質研究學會第30屆年會的研究，一項研究中的新的選擇性雌激素受體調節劑(SERM)顯示可以治療停經後婦女的骨質疏鬆症。
主要作者，舊金山協調中心創辦主任、加州大學舊金山分校醫學教授Steven Cummings 醫師在發表時表示，Lasofoxifene這一種SERM對於雌激素受體有很強的親合力，之前的研究顯示它可以減少骨骼代謝周轉，增加骨密度，減少LDL [低密度脂蛋白]膽固醇以及各種外陰道症狀。
Graham Russell醫師向Medscape醫學新聞表示，Lasofoxifene相當有趣，因為選擇性雌激素受體調節劑的研發是相當有吸引力的科學觀念；它是個老觀念，自從raloxifene之後沒有新藥也讓我們感到很訝異；Russell醫師是英國牛津大學Nuffield骨外科系肌肉骨骼藥理學教授，他主持發表lasofoxifene資料的這一段會議。
這項名為PEAL(Postmenopausal Evaluation and Risk-Reduction with Lasofoxifene)的試驗，共收納了8,556名婦女，年紀在59至80 歲，腰椎或者股骨頸的骨密度T-分數為–2.5 到 –4.5之間，隨機分派到接受每天一次的lasofoxifene 0.25 mg 、每天一次的lasofoxifene 0.5 mg或者安慰劑；所有病患每天接受1 g的鈣片和400-800 IU的維他命D；本試驗為期三年且有兩年的延伸期。
Cummings醫師根據治療意向分析發表治療後五年所收集的資料，整體來說，77%的參與者持續到五年，那些服用0.5 mg lasofoxifene者，選擇作為適當的臨床劑量，平均在脊椎和股骨頸的骨質密度增加約3%；相較於安慰劑組，她們也減少了42%的脊椎骨折風險和24%的非脊椎骨折風險(P < .001)。此外，服用0.5 mg lasofoxifene者的髖骨骨折率也減少，只是未達統計上的顯著意義。
高劑量lasofoxifene治療也減少了81%的雌激素受體(ER+)陽性乳癌風險(P < .001)，減少嚴重冠心病(CHD)事件風險達68% (P= .016)；雖然lasofoxifene的中風風險也降低，但缺血性中風的風險則與安慰劑組沒有差異。
Russell醫師表示，它優於raloxifene的好處是對於非脊椎骨折有好處，髖骨骨折未達顯著意義，但是看來比raloxifene有效，且它有其他好處，特別是心血管和乳癌方面的好處。
對於子宮內膜癌或子宮內膜增生的比率，高劑量lasofoxifene和安慰劑組之間並無差異；相較於安慰劑，0.5 mg lasofoxifene的靜脈血栓(VTE)比率大約兩倍；有趣的是，服用0.25 mg lasofoxifene者的死亡率略高於安慰劑組，但是高劑量lasofoxifene者和安慰劑組之間的死亡率則沒有差異。
Russell醫師表示，很清楚的，它有符合期望的安全議題；舉例來說，所有的SERMS和雌激素都有靜脈血栓的問題。
Cummings醫師表示，對於骨質疏鬆婦女，Lasofoxifene是新的且有效的SERM；在0.5 mg劑量，它減少了脊椎和非脊椎骨折、ER+ 乳癌、嚴重CHD事件和中風風險，但是它也增加了VTE風險。
本研究接受lasofoxifene的製造廠輝瑞藥廠贊助，Cummings醫師接受輝瑞藥廠的資金。
美國骨骼與礦物質研究學會 (ASBMR) 第30屆年會：摘要1288。發表於2008年9月16日。
Lasofoxifene May Soon Be New SERM on the Block
By Alison Palkhivala
Medscape Medical News
September 17, 2008 (Montreal, Quebec) ?An investigational new selective estrogen-receptor modulator (SERM) is showing promise in the treatment of osteoporosis among postmenopausal women, according to research presented here at the American Society for Bone and Mineral Research 30th Annual Meeting.
"Lasofoxifene, a SERM, has a very high affinity for the estrogen receptor, and previous studies have shown that it decreases bone turnover, increases bone density, and decreases LDL [low-density lipoprotein] cholesterol and all sorts of vulvovaginal [symptoms]," lead author Steven Cummings, MD, told the audience during his presentation. He is founding director of the San Francisco Coordinating Center and a professor of medicine at the University of California at San Francisco.
"Lasofoxifene is really interesting because the development of the selective estrogen-receptor modulators is a very attractive scientific idea." Graham Russell, MD, PhD, told Medscape Medical News. "It's an older idea, and many of us have been very surprised that there's been nothing [new] since raloxifene." Dr. Russell is a professor of musculoskeletal pharmacology at the Nuffield Department of Orthopaedic Surgery, University of Oxford, in England. He moderated the session in which the data on lasofoxifene were presented.
For the Postmenopausal Evaluation and Risk-Reduction with Lasofoxifene (PEAL) trial, 8556 women, aged 59 to 80 years, with T-scores at the lumbar spine or femoral neck between ?.5 and ?.5 were randomly assigned to receive lasofoxifene 0.25?mg once daily, lasofoxifene 0.5?mg once daily, or placebo. All patients also received 1?g of calcium and 400 to 800 IU of vitamin?D daily. This was a 3-year trial with a 2-year extension phase.
Dr. Cummings presented data collected after 5 years of therapy based on an intent-to-treat analysis. Overall, 77% of participants remained in the trial for the duration. Those taking the 0.5?mg dose of lasofoxifene, selected as the relevant clinical dose, had average increases in bone mineral density at the spine and femoral neck of about 3%. They also had a 42% reduced risk for vertebral fracture and a 24% reduced risk for nonvertebral fracture, compared with those on placebo (P?< .001). Although there was a trend toward reduced hip-fracture rates with 0.5?mg of lasofoxifene, compared with placebo, it did not reach statistical significance.
High-dose lasofoxifene therapy was also associated with an 81% reduced risk for estrogen-receptor positive (ER+) breast cancer (P?< .001), a 68% reduced risk for major coronary heart disease (CHD) events (P?= .016). Although the risk for stroke was also lower with lasofoxifene, the risk for transient ischemic attacks did not differ from the placebo group.
"The advantage of it over raloxifene is that it has an effect on nonvertebral fractures," said Dr. Russell. "It doesn't reach significance for hip fractures, but it seems to be more potent than raloxifene. And it has other benefits, particularly the cardiovascular benefits and the breast cancer benefits."
There were no differences between the patients on high-dose lasofoxifene and those on placebo with respect to rates of endometrial cancer or hyperplasia. Compared with placebo, the rate of venous thromboembolism (VTE), however, was about double for 0.5?mg of lasofoxifene. Interestingly, mortality rates were slightly higher among those taking the 0.25-mg dose of the drug than among those taking placebo, but there was no difference in mortality rates between those tsaking the high dose of lasofoxifene and those taking placebo.
"Clearly, it has the usually expected safety issues; for instance, venous thromboembolism ?the story that is there for all SERMS it seems, and for estrogen as well," said Dr. Russell.
"Lasofoxifene is a new and potent SERM for women with osteoporosis," said Dr. Cummings. "At the 0.5?mg dose, it reduces the risk for vertebral and nonvertebral fractures, ER+ breast cancer, major CHD events, and stroke, but it [also] increases the risk of VTE."
The study was funded by Pfizer, the manufacturer of lasofoxifene, and Dr. Cummings has received funding from Pfizer.
American Society for Bone and Mineral Research (ASBMR) 30th Annual Meeting: Abstract 1288. Presented September 16, 2008.
[ 本帖最後由 goodcat1111 於 2008-9-26 23:21 編輯 ] |
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