| <P style="TEXT-INDENT: 28pt; LINE-HEIGHT: 150%; TEXT-ALIGN: left" align=left><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">2011</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">年</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">6</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">月</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">9</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">日美国</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">FDA</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">发布安全性信息称，</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">5</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">α还原酶抑制剂类药物产品说明书的</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">[</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">警告和注意事项</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">]</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">部分进行了更新，以包含新的高分化前列腺癌风险增加的安全性信息。此风险虽然比较低，但是医护人员应了解此安全性信息，在开始或继续使用</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">5</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">α还原酶抑制剂治疗男性患者时应权衡已知的风险</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">/</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">效益比。</SPAN></P>
<P style="TEXT-INDENT: 28pt; LINE-HEIGHT: 150%; TEXT-ALIGN: left" align=left><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体"></SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">新的安全性信息是基于</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">FDA</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">对两项大型、随机对照临床试验</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">(</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">前列腺癌预防临床试验（</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">PCPT</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">）和度他雄胺减少前列腺癌事件（</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">REDUCE</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">）临床试验</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">)</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">评估后得出的。两项临床试验表明，非那雄胺</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">5mg</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">和度他雄胺治疗后前列腺癌的整体风险降低了，整体风险降低主要是由于低风险型的前列腺癌的发生率降低了。然而，两项试验均显示使用非那雄胺和度他雄胺治疗后高分化前列腺癌的发生率升高了。</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??"></SPAN></P>
<P style="TEXT-INDENT: 28pt; LINE-HEIGHT: 150%; TEXT-ALIGN: left" align=left><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">PCPT</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">是个随机、双盲、安慰剂对照、多中心、为期</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">7</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">年的临床试验，该试验纳入了</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">18</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">，</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">882</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">名</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">55</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">岁及以上直肠指检正常及</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">PSA</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">水平≤</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??"> 3 ng/mL </SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">的男性患者。那些存在前列腺癌高发风险的男性未纳入试验，如前列腺活检显示存在恶性前列腺上皮内肿瘤的男性。该试验对比了使用非那雄胺</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">5mg (n=9423)</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">与安慰剂</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">(n=9459)</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">相比前列腺癌风险的降低情况。</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">PCPT</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">的结果显示，男性使用非那雄胺与安慰剂相比前列腺癌的整体风险降低了</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">26%( p<0.0001)</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">。前列腺癌风险的降低局限在</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">Gleason</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">评分（</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">GS</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">）为</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">6</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">或更低的前列腺癌，然而，男性使用非那雄胺与安慰剂相比</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">GS</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">为</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">8</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">－</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">10</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">的前列腺癌的发生率增加了，非那雄胺是</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">1.8%</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">，安慰剂是</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">1.1%</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">。</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??"></SPAN></P>
<P style="TEXT-INDENT: 28pt; LINE-HEIGHT: 150%; TEXT-ALIGN: left" align=left><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">REDUCE</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">试验是随机、双盲、安慰剂对照的试验，研究度他雄胺用于降低</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">50</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">－</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">75</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">岁男性中活检确认的前列腺癌风险的有效性和安全性，该年龄段男性一般认为存在前列腺癌增加的风险。该试验纳入了</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">8231</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">男性，随机分为安慰剂组（</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">n=4126</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">）和度他雄胺</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">(n=4105)</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">组，度他雄胺</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">0.5mg</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">每日一次总共服用</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">4</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">年。在研究的第</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">2</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">年和第</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">4</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">年进行前列腺活检。</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??"> REDUCE</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">试验结果显示，使用度他雄胺的男性与使用安慰剂的男性相比活检确认的前列腺癌的整体风险降低了</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">23% (p<0.0001)</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">。此整体风险的降低局限在</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">GS6</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">或更低的前列腺癌，度他雄胺的</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">GS8</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">－</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">10</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">前列腺癌的发生率相对安慰剂反而增加了，分别为</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">1</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">％和</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">0.5%</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">。</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??"></SPAN></P>
<P style="TEXT-INDENT: 28pt; LINE-HEIGHT: 150%; TEXT-ALIGN: left" align=left><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">FDA</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">建议<A name=aihp></A>医护人员在开始</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">5-ARIs</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">治疗前，进行适当的评估来排除其他的泌尿科疾病，包括前列腺癌，可能与良性的前列腺增生相似。使用</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">5-ARIs</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">治疗后，前列腺特异抗原（</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">PSA</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">）值通常可以在</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">6</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">个月内降低</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">50</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">％，不过个体接受</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">5-ARIs</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">治疗的患者</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">PSA</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">值降低程度可能会有差异。因此，在使用</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">5-ARIs</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">期间，任何确认的</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">PSA</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">值升高可能是存在前列腺癌的信号，即使此</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">PSA</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">值是在未使用</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">5-ARIs </SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">的男性的正常范围内，都应进行评估。另外，</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">FDA</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">提示医护人员</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??">5-ARIs </SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: 宋体">未被批准用于前列腺癌的预防。</SPAN><SPAN style="LINE-HEIGHT: 150%; FONT-FAMILY: ??"></SPAN></P> |
