查看“维泽嘉”的源代码

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            <strong>[[维泽嘉]]</strong>（<strong>[[Vizimpro]]</strong>，通用名：<strong>[[达可替尼]]</strong>/<strong>[[Dacomitinib]]</strong>）是一种第二代、口服、高选择性的不可逆[[表皮生长因子受体]]（[[EGFR]]）[[酪氨酸激酶抑制剂]]（[[TKI]]）。作为[[泛HER]]家族抑制剂，它能与[[EGFR]]（[[HER1]]）、[[HER2]]和[[HER4]]的[[激酶结构域]]产生持久的[[共价结合]]。在2026年的[[肺癌]]诊疗共识中，[[维泽嘉]]被确立为治疗携带[[EGFR]]19因子[[缺失突变]]或21因子[[L858R]]置换突变的局部晚期或[[转移性]][[非小细胞肺癌]]（[[NSCLC]]）的一线核心药物。凭借其在[[ARCHER1050]]全球临床研究中展现出的卓越[[总生存期]]（[[OS]]）获益，[[维泽嘉]]成为精准打击[[EGFR]]敏感突变肺癌的里程碑式靶向药物。
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            <div style="font-size: 1.2em; font-weight: bold; letter-spacing: 1.2px;">[[维泽嘉]] (Vizimpro)</div>
            <div style="font-size: 0.7em; opacity: 0.85; margin-top: 4px;">[[达可替尼]]/[[Dacomitinib]] · 点击展开详情</div>
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                     <div style="width: 140px; height: 90px; background-color: #f1f5f9; display: flex; align-items: center; justify-content: center; color: #94a3b8; font-size: 0.8em; padding: 10px; text-align: center;">[[EGFR-TKI]]二代不可逆结合结构</div>
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                <div style="font-size: 0.8em; color: #64748b; margin-top: 12px; font-weight: 600;">核心靶点：[[EGFR]]/[[HER2]]/[[HER4]]</div>
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                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">1956([[EGFR]])</td>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">[[HGNC]]ID</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">3236</td>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">[[UniProt]]</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">P00533</td>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">[[分子量]]</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">468.9Da</td>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">[[给药途径]]</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #1e40af;">[[口服]]([[片剂]])</td>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569;">原研厂商</th>
                    <td style="padding: 12px; color: #0f172a;">[[辉瑞]]([[Pfizer]])</td>
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        [[维泽嘉]]属于第二代[[EGFR-TKI]]，其生化机制显著优于传统的第一代可逆性抑制剂：
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        <li style="margin-bottom: 12px;"><strong>[[不可逆结合]]：</strong>[[达可替尼]]与[[EGFR]]、[[HER2]]及[[HER4]]激酶结构域的[[ATP]]结合位点发生[[共价结合]]。这种物理性质的锁定使受体发生永久性失活，只有待新的受体蛋白合成后信号传导才可能恢复，从而实现了更持久的[[信号抑制]]。</li>
        <li style="margin-bottom: 12px;"><strong>[[广谱靶向]]：</strong>通过同时打击[[HER家族]]的多个成员，[[维泽嘉]]能有效遏制由[[HER2]]或[[HER4]]介导的代偿性信号旁路激活，全方位封锁驱动肿瘤生长的[[MAPK通路]]和[[PI3K/Akt通路]]。</li>
        <li style="margin-bottom: 12px;"><strong>深度抑制[[L858R]]：</strong>在分子动力学模拟中，[[维泽嘉]]对[[EGFR]]21因子[[L858R]]突变蛋白展现出极高的结合亲和力，这解释了其在临床亚组中表现出的优异疗效。</li>
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                <th style="padding: 10px; border: 1px solid #cbd5e1; color: #0f172a; width: 25%;">试验名称</th>
                <th style="padding: 10px; border: 1px solid #cbd5e1; color: #475569;">研究背景与人群</th>
                <th style="padding: 10px; border: 1px solid #cbd5e1; color: #1e40af;">关键数据亮点</th>
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                <td style="padding: 8px; border: 1px solid #cbd5e1; font-weight: 600;">[[ARCHER1050]]</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">一线治疗[[EGFR]]阳性[[晚期NSCLC]] (对比[[吉非替尼]])。</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">[[PFS]]显著延长(14.7 vs 9.2个月)；[[OS]]历史性达到34.1个月。</td>
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                <td style="padding: 8px; border: 1px solid #cbd5e1; font-weight: 600;">[[L858R]]专项分析</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">针对[[EGFR]]21外显子突变亚组。</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">在[[L858R]]人群中展现出比一代[[TKI]]更稳健的生存获益趋势。</td>
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    <h2 style="background: #f1f5f9; color: #0f172a; padding: 10px 18px; border-radius: 0 6px 6px 0; font-size: 1.25em; margin-top: 40px; border-left: 6px solid #0f172a; font-weight: bold;">诊疗策略：个体化滴定与毒性管理</h2>
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        鉴于[[维泽嘉]]较强烈的[[靶向毒性]]，2026年的临床策略强调“<strong>[[剂量减量不减效]]</strong>”的原则：
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        <li style="margin-bottom: 12px;"><strong>[[剂量递减]]策略：</strong>标准起始剂量为45mg/日。若患者出现严重的[[腹泻]]、[[皮疹]]或[[甲沟炎]]，应及时下调至30mg或15mg。临床证据证实，合理的剂量调整能显著提高[[依从性]]，且不损害最终的[[生存获益]]。</li>
        <li style="margin-bottom: 12px;"><strong>[[皮肤副作用]]防治：</strong>建议在用药初期即使用[[润肤剂]]预防皮肤干燥。针对[[甲沟炎]]，需保持指甲修剪整齐并预防性应用[[抗生素软膏]]。</li>
        <li style="margin-bottom: 12px;"><strong>[[腹泻]]干预：</strong>发生[[腹泻]]时应立即启用[[洛哌丁胺]]等止泻药物，并进行[[脱水]]预防。</li>
        <li style="margin-bottom: 12px;"><strong>[[耐药后处理]]：</strong>若治疗后出现进展，应立即进行[[液体活检]]（[[ctDNA]]）检测是否存在[[T790M]]突变，以决定是否序贯应用[[奥希替尼]]。</li>
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            <li style="margin-bottom: 8px;"><strong>[[EGFR突变]]：</strong>[[亚洲]]肺腺癌患者中最主要的[[驱动基因]]，是[[维泽嘉]]起效的前提。</li>
            <li style="margin-bottom: 8px;"><strong>[[ARCHER1050]]：</strong>[[维泽嘉]]获批进入全球指南的基石性[[III期研究]]。</li>
            <li style="margin-bottom: 8px;"><strong>[[奥希替尼]] (Osimertinib)：</strong>第三代[[EGFR-TKI]]，常作为二代[[TKI]]耐药后的救治方案。</li>
            <li style="margin-bottom: 8px;"><strong>[[不可逆抑制剂]]：</strong>通过形成[[化学共价键]]永久锁定靶标蛋白的一类高效药物。</li>
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        <span style="color: #0f172a; font-weight: bold; font-size: 1.05em; display: inline-block; margin-bottom: 15px;">学术参考文献与权威点评</span>
        
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            [1] <strong>Wu YL, et al. (2017).</strong> <em>Dacomitinib versus gefitinib as first-line treatment for patients with EGFR-mutation-positive non-small-cell lung cancer (ARCHER 1050).</em> <strong>[[The Lancet Oncology]]</strong>.[Academic Review]<br>
            <span style="color: #475569;">[权威点评]：该项研究首次在大样本量临床中确立了二代不可逆TKI在延长一线PFS上的显著优势。</span>
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            [2] <strong>Mok TS, et al. (2018).</strong> <em>Improvement in Overall Survival in a Randomized Phase III Study of Dacomitinib vs Gefitinib in Patients With Advanced NSCLC.</em> <strong>[[Journal of Clinical Oncology]]</strong>.<br>
            <span style="color: #475569;">[核心价值]：生存突破。研究数据证明了达可替尼能够为EGFR敏感突变患者提供长达34个月以上的总生存获益。</span>
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            [[维泽嘉]] ([[Vizimpro]]) 诊疗生态 · 知识图谱
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                <td style="width: 85px; background-color: #f8fafc; color: #334155; font-weight: 600; padding: 10px 12px; text-align: right; vertical-align: middle; white-space: nowrap;">关联靶点</td>
                <td style="padding: 10px 15px; color: #334155;">[[EGFR]]•[[HER2]]•[[HER4]]•[[ATP结合位点]]•[[共价键]]</td>
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                <td style="padding: 10px 15px; color: #334155;">[[吉非替尼]]•[[阿法替尼]]•[[奥希替尼]]•[[洛哌丁胺]]</td>
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                <td style="width: 85px; background-color: #f8fafc; color: #334155; font-weight: 600; padding: 10px 12px; text-align: right; vertical-align: middle; white-space: nowrap;">核心突变</td>
                <td style="padding: 10px 15px; color: #334155;">[[19号外显子缺失]]•[[21号外显子L858R]]•[[T790M耐药突变]]</td>
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                <td style="width: 85px; background-color: #f8fafc; color: #334155; font-weight: 600; padding: 10px 12px; text-align: right; vertical-align: middle; white-space: nowrap;">研究前沿</td>
                <td style="padding: 10px 15px; color: #334155;">[[脑转移渗透性研究]]•[[联合免疫治疗探索]]•[[序贯方案的最优化路径分析]]</td>
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