荷爾蒙治療會增加前列腺癌與心臟病男性的死亡風險


  August 26, 2009 – 對於局部惡化的前列腺癌,使用新加入的荷爾蒙治療會造成有冠狀動脈疾病病史之男性的死亡風險增加將近兩倍。
  
  此一發現來自一篇有5,077名以近接治療(brachytherapy)治療其癌症之研究對象的回溯研究,其中30%接受新加入的荷爾蒙治療,平均療程4個月。
  
  這個荷爾蒙治療包括促性腺釋放激素致效劑(leuprolide或goserelin)以及非類固醇抗男性荷爾蒙(bicalutamide或flutamide)。
  
  就資料好的一面看來,使用荷爾蒙治療、沒有心血管共病症或只有一個冠狀動脈疾病風險因素,如糖尿病、高膽固醇血症或高血壓的男性,各種原因死亡率並未增加。抽菸與家族心臟病史並未被視為風險因素。
  
  該研究發表於8月26日的美國醫學會期刊(Journal of the American Medical Association)。
  
  研究作者們在Medscape Oncology的訪問中強調,研究中只有5%的男性有冠狀動脈疾病(鬱血性心衰竭或曾心臟病發作)。
  
  麻州達那-法柏癌症研究治療中心與布萊根婦女醫院的Akash Nanda博士表示,我們的結果認為,對於這些男性,在他們考慮荷爾蒙治療之前,要先由一線照護的醫師和/或心臟專家評估,是否使用荷爾蒙治療他們的前列腺癌,或確認他們是否原本就有心臟病。
  
  Nanda博士承認,不曉得治療心臟病是否可以改善結果。他表示,研究並未指出治療冠狀動脈疾病是否可改變這些病患的風險。
  
  Nanda博士與共同作者結論表示,本研究加強了新加入荷爾蒙治療對於特定男性之可能傷害的警覺。
  
  【研究細節】
  Nanda博士觀察發現,許多臨床研究顯示,將荷爾蒙治療加到侵襲性前列腺癌之放射治療療程中,可以增加存活。不過,最近有一篇分析(JAMA. 2008:299:289-295)指出,這可能不適合那些同時有其他疾病的男性。這篇新研究的目的在於確認共病症是否會影響存活。
  
  為此,研究者探究於1997至2006年間在芝加哥前列腺癌中心接受治療的5,077名臨床分期T1到T3 N0 M0之前列腺癌病患,被轉診到此癌症中心的男性都是對於近接治療有興趣或適合此方式的病患。
  
  這些男性中,2,653人(52.3%)沒有心血管共病症病史,2,168人(42.7%)有冠狀動脈疾病風險因素,256人(5%)有冠狀動脈疾病。這些男性的平均年紀是69.5歲,557人(10.9%)接受追加體外射線。
  
  研究中的多數男性(70%)並未接受新加入的荷爾蒙治療,作為那些有使用者的對照組。
  
  對於沒有共病症的男性,使用新加入的荷爾蒙治療,在平均追蹤5.0年和4.4年之後,並未顯著增加各種原因的死亡率(9.6% vs 6.7%;校正風險比[HR]0.97;95%信心區間[CI]0.72- 1.32;P= .86)或單一冠狀動脈疾病風險因素(10.7% vs 7.0%;校正HR,1.04;95% CI,0.75-1.43;P=.82)。
  
  不過,對於有冠狀動脈疾病的男性,該治療與顯著增加各種原因的死亡率風險有關(26.3% vs 11.2%;校正HR,1.96;95% CI,1.04- 3.71;P=.04)。這些男性的平均追蹤期間為5.1年。
  
  研究期間,研究者校正了年紀、治療幾年、追加體外射線、治療傾向分數、已知的前列腺癌預後因素(例如Gleason評分),才獲得前述結果。
  
  作者們也指出,在其他不同條件的研究中,荷爾蒙治療與各種副作用有關,包括增加心血管死亡風險。
  
  【更多的臨床意義】
  Nanda博士等人建議,對於有可接受之前列腺癌風險因素和冠狀動脈疾病病史的男性,應考慮近接治療以及荷爾蒙治療之外的療法。這些包括主動式監測、只用體外放射線治療、以及前列腺切除術。Nanda博士解釋,對這類男性,在使結果最大化方面,其實不需要荷爾蒙治療。相反的,使用荷爾蒙治療減少腺體體積,確保近接治療不會被恥骨弓影響。
  
  不過,對於有不可接受之前列腺癌風險的男性,荷爾蒙治療可提供存活利益。Nanda博士表示,這是更棘手的決定,因為需要荷爾蒙治療來使結果最大化。荷爾蒙治療的利弊之間必須取得平衡;如前所述,這類病患開始荷爾蒙治療之前需要有適當的醫療評估或治療。
  
  Nanda博士指出,研究發現僅限於近接治療,因此,無法推論到以體外放射線治療的前列腺癌男性。他表示,需要其他研究來確認用於其他病患的發現。
  
  作者們也指出,荷爾蒙治療的期間和範圍也都是研究變項。他們寫道,局部惡化前列腺癌的男性,經常以2到3年的荷爾蒙治療合併體外放射線治療。
  
  研究者皆宣告沒有相關財務關係。
  

Hormone Therapy May Increase Risk for Death in Men With Prostate Cancer and Heart Disease

By Nick Mulcahy
Medscape Medical News

August 26, 2009 – In localized or locally advanced prostate cancer, the use of neoadjuvant hormone therapy was associated with a nearly 2-fold risk for death in men who also had a history of coronary artery disease.

This finding comes from a retrospective study of 5077 men who were treated with brachytherapy for their cancer, 30% of whom received neoadjuvant hormone therapy for a median treatment duration of 4 months.

The hormone therapy consisted of both a luteinizing hormone-releasing hormone agonist (leuprolide or goserelin) and a nonsteroidal antiandrogen (bicalutamide or flutamide).

On the bright side of the data, there was no increase in all-cause mortality among men treated with hormone therapy who had either no cardiovascular comorbidity or a single coronary artery disease risk factor, such as diabetes mellitus, hypercholesteremia, or hypertension. Smoking and a family history of heart disease were not evaluated as risk factors.

The study was published in the August 26 issue of the Journal of the American Medical Association.

In an interview with Medscape Oncology, the study's lead author stressed that only 5% of the men in the study — a "small subgroup" — had coronary artery disease (congestive heart failure or past heart attack).

"Our results suggest that for these men, either hormonal therapy not be used in the treatment of their prostate cancer or their underlying heart disease be addressed by a primary-care physician and/or a cardiologist before they are considered for hormonal therapy," said Akash Nanda, MD, PhD, from Brigham and Women's Hospital and the Dana-Farber Cancer Institute in Boston, Massachusetts.

This study should heighten awareness about the potential for harm with neoadjuvant hormone therapy in select men.

Dr. Nanda acknowledged that it is not known if treatment for heart disease would improve outcome. "The study does not address whether or not treatment for coronary artery disease potentially changes the risk for these patients," he said.

Dr. Nanda and his coauthors concluded that "this study should heighten awareness about the potential for harm with neoadjuvant hormone therapy in select men."

Study Details

Several clinical trials have shown that adding hormonal therapy to radiation therapy in the treatment of aggressive prostate cancer leads to an increase in survival, observed Dr. Nanda. However, a recent analysis (JAMA. 2008:299:289-295) indicated that "this may not be the case for men with coexisting illnesses," according to Dr. Nanda. The purpose of the new study was to identify comorbidities that might affect survival.

To that end, the investigators looked at 5077 men with clinical stage?T1 to T3 N0 M0 prostate cancer treated between 1997 and 2006 at the Chicago Prostate Cancer Center, a community practice in Westmont, Illinois. Men were referred to this center on the basis of their interest in or candidacy for brachytherapy.

Among the men, 2653 (52.3%) had no history of a cardiovascular comorbidity, 2168 (42.7%) had a coronary artery disease risk factor, and 256 (5%) had coronary artery disease. The median age of the men was 69.5 years, and 557 (10.9%) had received supplemental external-beam radiation.

Most of the men in the study (70%) did not receive neoadjuvant hormone therapy and served as comparators for the men who did.

Neoadjuvant hormone therapy use was not significantly associated with an increased risk for all-cause mortality in men with no comorbidity (9.6% vs 6.7%; adjusted hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.72?- 1.32; P?= .86) or a single coronary artery disease risk factor (10.7% vs 7.0%; adjusted HR, 1.04; 95% CI, 0.75?- 1.43; P?= .82) after median follow-ups of 5.0 and 4.4 years, respectively.

However, for men with coronary artery disease, the therapy was significantly associated with an increased risk for all-cause mortality (26.3% vs 11.2%; adjusted HR, 1.96; 95% CI, 1.04?- 3.71; P?= .04). These men had a median follow-up of 5.1 years.

In arriving at these findings, the investigators adjusted for age, treatment year, supplemental external-beam radiation therapy, treatment propensity score, and known prostate cancer prognostic factors (such as Gleason score).

The authors also noted that, in other research in different settings, hormone therapy has been associated with a variety of adverse effects, including increased risk for cardiovascular death.

More on Clinical Significance

Dr. Nanda and his colleagues recommend that, in men with favorable-risk prostate cancer and a history of coronary artery disease, alternative strategies to brachytherapy and hormone therapy be considered. These include active surveillance, treatment with external-beam radiation alone, and prostatectomy. In such men, hormone therapy is not really needed to "maximize outcome" anyway, explained Dr. Nanda. Instead, hormone therapy is used to reduce the size of the gland, ensuring that brachytherapy is not obstructed by the arch of the pubic bone.

Hormone therapy is needed to maximize outcome.

However, in men with unfavorable-risk prostate cancer, hormone therapy offers a survival benefit. "This is a tougher decision because hormone therapy is needed to maximize outcome," said Dr. Nanda. The risks and benefits of hormone therapy must be balanced; as noted above, appropriate medical evaluation or treatment is needed before hormone therapy is used in this setting, Dr. Nanda said.

Dr. Nanda also pointed out that the findings were limited to brachytherapy and, as a result, not necessarily generalizable to men with prostate cancer who are treated with external-beam radiation. "Other investigators will want to validate these findings in other settings," he said.

The authors also note that the duration and extent of hormone therapy are variables in need of study. "Men with locally advanced prostate cancer are frequently treated with 2 to 3 years of hormone therapy in combination with external-beam radiation therapy," they write.

The researchers have disclosed no relevant financial relationships.

JAMA. 2009;302:866-873.

    
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