本帖最後由 lsc0019 於 2009-6-15 23:13 編輯
作者：Zosia Chustecka
出處：WebMD醫學新聞
May 31, 2009 (佛州奧蘭多) — 研究發現停經後婦女使用荷爾蒙替代療法(HRT)的另一個副作用，併用黃體素與雌激素治療會增加非小細胞肺癌(NSCLC)的死亡風險。
這項發現來自婦女健康提倡協會(WHI)研究的二度分析，該研究發現，在服用荷爾蒙的抽菸者中，有百分之一在研究的8年間發生原可避免的死亡。
領銜作者、Harbor-UCLA醫學中心、洛杉磯生物醫學研究中心腫瘤內科醫師Rowan Chlebowski博士表示，對於症狀治療來說，百分之一的死亡率是相當巨大的。
Chlebowski博士向Medscape Oncology表示，訊息清楚表達出不要抽菸以及服用荷爾蒙。他指出，另外則是，已經服用荷爾蒙且診斷有NSCLC的婦女，停止服用荷爾蒙。
Chlebowski博士在美國臨床腫瘤協會第45屆年會記者會中發言。
記者會主持人、達那-法柏哈佛醫學中心肺癌計畫主持人Bruce Johnson醫師解釋，這些發現是明確的，因為它們來自隨機臨床試驗，試驗中區別出荷爾蒙的影響。之前許多有關荷爾蒙與肺癌的資料是來自案例控制研究。也有臨床前資料認為，雌激素會增加肺癌生長，所以這項發現在病理生理觀點上，有其道理。
Johnson醫師指出，新資料顯示NSCLC死亡率增加，將是另一個不要服用荷爾蒙的原因。
Chlebowski博士表示，我們已經知道合併荷爾蒙治療的弊大於利，包括中風與乳癌風險增加。這些新資料顯示出與NSCLC死亡的關聯，對於醫師和婦女考量使用荷爾蒙治療時將有所影響，特別是有抽菸史的婦女。
他表示，美國目前約有15%的停經後婦女使用HRT，在2002年前約有半數，當時，WHI研究因為HRT副作用而提早終止。美國約有15%的停經後婦女抽菸。
【對於NSCLC有影響、SCLC則無】
WHI研究總共有16,608名多數健康的停經後婦女，這些婦女的年齡在50至79歲，研究人員將她們隨機分派接受安慰劑或含有合成馬雌激素(0.625 mg) 與medroxyprogesterone acetate (2.5 mg)的併用荷爾蒙治療；這兩組的其他因素(包括抽菸)比率相當。
在試驗後5.6年以及後續2.4年追蹤之後進行對肺癌的分析。兩組的小細胞肺癌(SCLC)發生率與因為SCLC死亡的比率差不多。NSCLC的發生率顯示，荷爾蒙組有不顯著的增加傾向，但荷爾蒙組在NSCLC診斷後的死亡率顯著比安慰劑組增加(分別是46.3% 與27%；風險比[HR])為1.59；P= .04)。
Chlebowski博士表示，因此，服用荷爾蒙的婦女比安慰劑組婦女更可能死於NSCLC (p=.02)。
Chlebowski博士也發表其他數據如下：
* 對所有研究對象，荷爾蒙組8,052人中有67人死亡，安慰劑組7,678人中有39人死亡(HR，1.61)。
* 對於未曾抽菸的婦女，荷爾蒙組4,178人中有9人死亡，安慰劑組3,999人中有5人死亡(HR，1.67)。
* 對於以前曾抽菸的婦女，荷爾蒙組3,362人中有29人死亡，安慰劑組3,157人中有15人死亡(HR，1.83)。
* 對於目前抽菸的婦女，荷爾蒙組800人中有27人死亡，安慰劑組838人中有19人死亡。
根據現有抽菸者的資料，Chlebowski博士估計每800人的死亡案例相差8件，也就是抽菸者的死亡率增加百分之一的風險。
未參與本研究的約翰霍普金斯大學助理教授Julie Brahmer醫師獲邀對Medscape Oncology發表評論時表示，該發現是「有趣的」。之前的研究暗示，服用荷爾蒙的婦女，其肺癌發生率增加，但這項研究顯示的是死於NSCLC的風險增加。
Brahmer醫師指出，當我們坐下來和病患談論荷爾蒙治療的利弊，並懷疑是否值得時，這增加了我們和病患討論時的可信度。
對於已經診斷有肺癌的婦女，Brahmer醫師表示，她的建議是不要服用荷爾蒙、或者停用，但她指出，每個病患都需個別考量，考量有多少破壞生活品質的停經後症狀。
Chlebowski博士也強調這一點，並指出，在WHI研究中，約有30%診斷有NSCLC的婦女繼續服用荷爾蒙。他表示，根據現有資料，這些病患應該停藥。
Chlebowski博士曾經擔任Amgen、Eli Lilly、Wyeth、AstraZeneca以及Novartis的顧問或者諮詢人員，也接受過獎助金。Johnson醫師曾經擔任Genzyme的顧問或諮商；擁有Boston Scientific、Celgene以及Johnson & Johnson的股票選擇權；接受授權Genzyme進行EGFR突變檢測的權利金。Brahmer醫師擔任AstraZeneca、Eli Lilly以及 ImClone的顧問。
美國臨床腫瘤協會(ASCO)第45屆年會：摘要CRA1500。發表於2009年5月30日。
ASCO 2009: HRT Increases Risk for Death from Non-Small-Cell Lung Cancer
By Zosia Chustecka
Medscape Medical News
May 31, 2009 (Orlando, Florida) — Another adverse effect from hormone replacement therapy (HRT) in postmenopausal women has emerged — the use of combined progestin and estrogen hormone therapy increases the risk for death from non-small-cell lung cancer (NSCLC).
The finding comes from a secondary analysis of the Women's Health Initiative (WHI) study, which found that among current smokers who were using hormones, 1 in 100 experienced an avoidable death during the 8 years of the study.
"One in 100 is a colossal mortality for a treatment that is used for symptom management," said lead author Rowan Chlebowski, MD, PhD, medical oncologist at the Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center.
The clear message is don't smoke and take hormones.
"The clear message is don't smoke and take hormones," Dr. Chlebowski told Medscape Oncology .The other message is that women who are taking hormones and who are diagnosed with NSCLC should stop taking the hormones, he added.
Dr. Chlebowski was speaking at a press conference here at the American Society of Clinical Oncology 45th Annual Meeting, where he presented the findings.
The moderator of the press briefing, Bruce Johnson, MD, director of the Dana-Farber Harvard Medical Center Lung Cancer Program, in Boston, Massachusetts, explained that these findings are robust because they come from a randomized clinical trial, where the effect of hormones was isolated. Many of the previous data about hormones and lung cancer have come from case–control studies. There are also preclinical data suggesting that estrogen can increase the growth of lung cancer, and so the finding "makes a lot of sense from a pathophysiological standpoint."
The new data showing an increase in mortality from NSCLC are "yet another reason not to take hormones," Dr. Johnson noted.
"We already know that combined hormone therapy has more risks than benefits, including a higher risk of stroke and breast cancer," said Dr. Chlebowski. These new data showing a link with death from NSCLC "should influence discussions between physicians and women considering hormone therapy use, especially those with a smoking history," he added.
About 15% of postmenopausal women in the United States currently use HRT, he said, which is about half the number doing so before 2002, when the WHI study was stopped prematurely because of the adverse effects of HRT. About 15% of postmenopausal women in the United States smoke, he added .
Effect on NSCLC, but Not on SCLC
The WHI was conducted in 16,608 mostly healthy postmenopausal women, aged 50 to 79 years, who were randomized to receive either placebo or combined hormone therapy with conjugated equine estrogen (0.625?mg) and medroxyprogesterone acetate (2.5?mg). The 2 groups were well balanced for all factors, including smoking.
The analysis for lung cancer was carried out after 5.6 years on the trial intervention and 2.4 years of additional follow-up. The incidence of small-cell lung cancer (SCLC) and deaths from SCLC were similar in the 2 groups. The incidence of NSCLC showed a nonsignificant trend toward an increase in the hormone group, whereas mortality after NSCLC diagnosis was significantly higher in the hormone group than in the placebo group (46.3% vs 27%, respectively; hazard ratio [HR], 1.59; P?= .04).
As a result, women taking hormones were more likely to die from NSCLC than those taking placebo (p=.02), Dr. Chlebowski reported.
Dr. Chlebowski also presented absolute numbers:
For all participants, there were 67 deaths in the 8052 patients in the hormone group and 39 deaths in the 7678 patients in the placebo group (HR, 1.61).
For women who had never smoked, there were 9 deaths in the 4178 patients in the hormone group and 5 deaths in the 3999 patients in the placebo group (HR, 1.67).
For women who had smoked in the past, there were 29 deaths in the 3362 patients in the hormone group and 15 deaths in the 3157 patients in the placebo group (HR, 1.83).
For current smokers, there were 27 deaths in the 800 patients in the hormone group and 19 deaths in the 838 patients in the placebo group.
?
It was from the figures for current smokers that Dr. Chlebowski estimated the difference of 8 deaths in approximately 800 women, giving an excess risk for mortality of 1 in 100.
Asked to comment by Medscape Oncology, Julie Brahmer, MD, assistant professor at Johns Hopkins University in Baltimore, Maryland, who was not involved in the study, said the finding is "intriguing." Previous studies have hinted at an increase in the incidence of lung cancer in women taking hormonal therapy, but this study shows an increase in the risk of dying from NSCLC, she said.
"It adds credence to our discussions with patients," Dr. Brahmer added, "for when we sit down to discuss the pros and cons of hormone therapy, and ask: Is it worth it?"
For women who have been diagnosed with lung cancer, Dr. Brahmer said her advice is not to take hormones, or to stop taking them, although she added that each case has to be considered individually, to take into account how many postmenopausal symptoms are disrupting quality of life.
Dr. Chlebowski also emphasized this point, and noted that in the WHI study, about 30% of women who were diagnosed with NSCLC continued to take hormones. "The message now is that these patients should stop taking them," he said.
Dr. Chlebowski has acted as a consultant or in an advisory role and has received honoraria from for Amgen, Eli Lilly, Wyeth, AstraZeneca, and Novartis. Dr. Johnson has acted in a consultancy or advisory role with Genzyme; has stock ownership in Boston Scientific, Celgene, and Johnson & Johnson; and receives royalty payments from a license to Genzyme for doing EGFR mutation testing. Dr. Brahmer has acted as an adviser to AstraZeneca, Eli Lilly, and ImClone.
American Society of Clinical Oncology (ASCO) 45th Annual Meeting: Abstract CRA1500. Presented May 30, 2009. |
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