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<P style="LAYOUT-GRID-MODE: char; TEXT-INDENT: 28pt; LINE-HEIGHT: 150%"><SPAN>在发送给《新英格兰医学杂志》编辑的信函中，美国食品药品监督管理局（<SPAN>FDA</SPAN>）的<SPAN>Diane Wysowski</SPAN>博士建议研究口服双膦酸盐是否是食道癌的潜在风险因素。<SPAN></SPAN></SPAN></P>
<P style="LAYOUT-GRID-MODE: char; TEXT-INDENT: 28pt; LINE-HEIGHT: 150%"><SPAN>Wysowski</SPAN><SPAN>博士表示，自<SPAN>1995</SPAN>年<SPAN>10</SPAN>月阿仑膦酸（<SPAN>alendronic acid</SPAN>，<SPAN>Fosamax</SPAN>）上市以来至<SPAN>2008</SPAN>年<SPAN>5</SPAN>月中旬，<SPAN>FDA</SPAN>收到报告：美国有<SPAN> 23</SPAN>例患者被诊断出食道癌，<SPAN>21</SPAN>例将阿仑膦酸作为怀疑药，<SPAN>2</SPAN>例将其作为并用药，其中包括<SPAN>8</SPAN>例死亡病例。<SPAN>FDA</SPAN>不良事件报告系统没有收到与其他口服双膦酸盐药物相关的类似报告。<SPAN></SPAN></SPAN></P>
<P style="LAYOUT-GRID-MODE: char; TEXT-INDENT: 28pt; LINE-HEIGHT: 150%"><SPAN>在上述<SPAN>23</SPAN>例患者中，<SPAN>19</SPAN>例中位年龄为<SPAN>74</SPAN>岁（平均年龄为<SPAN>71.8</SPAN>岁），<SPAN>78%</SPAN>为女性。阿仑膦酸的使用剂量为<SPAN>10mg/</SPAN>天（<SPAN>8</SPAN>例）、<SPAN>70mg/</SPAN>周（<SPAN>5</SPAN>例）或每周一次（<SPAN>1</SPAN>例），其他患者用量不详。<SPAN>16</SPAN>例患者从开始用药到发现肿瘤的中位时间为<SPAN>2.1</SPAN>年（平均时间为<SPAN>3</SPAN>年）。有<SPAN>1</SPAN>例</SPAN><SPAN>患者尽管患有巴雷特氏食<SPAN>管（<SPAN>Barrett</SPAN></SPAN></SPAN><SPAN style="FONT-FAMILY: Arial">’</SPAN><SPAN>s esophagus</SPAN><SPAN>），但也服用了阿仑膦酸。在<SPAN>6</SPAN>例患者中，主要病变部位发生在食管末端，也有一些病例累及到胃部。分别在<SPAN>7</SPAN>例患者和<SPAN>1</SPAN>例患者中发现了腺癌和鳞癌。<SPAN></SPAN></SPAN></P>
<P style="LAYOUT-GRID-MODE: char; TEXT-INDENT: 28pt; LINE-HEIGHT: 150%"><SPAN>据<SPAN>Wysowski</SPAN>介绍，在欧洲和日本已接到了<SPAN>31</SPAN>例患者在服用了阿仑膦酸后被诊断出食道癌的报告，其中<SPAN>21</SPAN>例怀疑与阿仑膦酸有关。在这些病例中，有<SPAN>6</SPAN>例怀疑与使用利塞膦酸（<SPAN>risedronate</SPAN>，<SPAN>Actonel</SPAN>）、依班膦酸（<SPAN>ibandronate</SPAN>，<SPAN>Boniva</SPAN>）、依替膦酸（<SPAN>etidronate</SPAN>，<SPAN>Didronel</SPAN>）或并用这些药物有关。在<SPAN>4</SPAN>例患者中双膦酸盐作为并用药使用。报告</SPAN><SPAN>中包括<SPAN>6</SPAN>例死亡病例。在这<SPAN>31</SPAN>例患者中，<SPAN>71%</SPAN>为女性，<SPAN>25</SPAN>例患者的中位年龄和平均年龄都是<SPAN>68.5</SPAN>岁。已知的<SPAN>20</SPAN>例患者用药剂量如下：阿仑膦酸<SPAN>10mg/</SPAN>天（<SPAN>9</SPAN>例）或<SPAN>70mg/</SPAN>周（<SPAN>8</SPAN>例）；利塞膦酸<SPAN>5mg/</SPAN>天（<SPAN>1</SPAN>例）或<SPAN>35mg/</SPAN>周（<SPAN>1</SPAN>例）；以及在使用依替膦酸数年后，服用依班膦酸<SPAN>150mg/</SPAN>月（<SPAN>1</SPAN>名）。<SPAN>21</SPAN>例患者从用药到发现肿瘤的中位时间为<SPAN>1.3</SPAN>年（平均时间为<SPAN>2.2</SPAN>年）。其中有<SPAN>3</SPAN>例患者在服用阿仑膦酸后被诊断出巴雷特氏食管，与发现食道癌的时间相似。<SPAN>8</SPAN>例患者的食道末端受到影响，<SPAN>4</SPAN>例累及胃部。分别在<SPAN>6</SPAN>例患者和<SPAN>5</SPAN>例患者中发现了腺癌和鳞癌。<SPAN></SPAN></SPAN></P>
<P style="LAYOUT-GRID-MODE: char; TEXT-INDENT: 26pt; LINE-HEIGHT: 150%"><SPAN style="LETTER-SPACING: -0.5pt">Wysowski</SPAN><SPAN style="LETTER-SPACING: -0.5pt">博士建议避免给巴雷特氏食管的患者开具口服双膦酸<SPAN>盐处方。<SPAN></SPAN></SPAN></SPAN></P>
<P style="LAYOUT-GRID-MODE: char; TEXT-INDENT: 28.1pt; LINE-HEIGHT: 150%"><B><SPAN>参考信息：</SPAN></B><SPAN><SPAN style="FONT-SIZE: 8pt; LINE-HEIGHT: 150%">Wysowski DK.Reports of esophageal cancer with oral bisphosphonate use. New England Journal of Medicine 360: 89-90, No. 1, 1 Jan 2009</SPAN></SPAN></P>
<P style="LAYOUT-GRID-MODE: char; TEXT-INDENT: 16pt; LINE-HEIGHT: 150%; TEXT-ALIGN: right" align=right><SPAN><SPAN style="FONT-SIZE: 8pt; LINE-HEIGHT: 150%">（<SPAN><FONT size=2>Reaction Weekly No.1235</FONT></SPAN>）<SPAN></SPAN></SPAN></SPAN></P> |
