预约演示
更新于：2025-12-12
Capecitabine
卡培他滨
更新于：2025-12-12
概要
基本信息
非在研机构 |
最高研发阶段批准上市 |
首次获批日期 美国 (1998-04-30), |
最高研发阶段(中国)批准上市 |
特殊审评加速批准 (美国) |
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结构/序列
分子式C15H22FN3O6 |
InChIKeyGAGWJHPBXLXJQN-UORFTKCHSA-N |
CAS号154361-50-9 |
关联
2,388
项与 卡培他滨 相关的临床试验NCT07243938
A Prospective, Multi-cohort Clinical Study to Explore the Preliminary Efficacy and Safety of Zanidatamab in Combination With Tislelizumab for HER2-Positive GI Tumors: the UNION-HER2-BASKET Study
This study is a prospective, multi-cohort clinical trial designed to evaluate the preliminary efficacy and safety of zanidatamab in combination with tislelizumab and chemotherapy/radiotherapy for patients with HER2-positive locally advanced or metastatic gastrointestinal tumors.
开始日期2026-01-15 |
申办/合作机构- |
NCT07113275
A National Multicenter, Randomized Controlled Phase III Clinical Trial Comparing Long-Course Versus Short-Course Radiotherapy Followed by Immunotherapy Combined With Total Neoadjuvant Therapy (TNT) to Long-Course Radiotherapy Followed by TNT in High-Risk Locally Advanced Rectal Cancer
This study is a national multicenter, prospective randomized controlled Phase III clinical trial designed to investigate the potential therapeutic benefit of immunotherapy combined with total neoadjuvant therapy (TNT) and to compare the efficacy of different radiotherapy modalities followed by immunotherapy.
开始日期2026-01-01 |
申办/合作机构- |
NCT07239466
A Single-Arm, Single-Center Study of Exploring the β-hydroxybutyrate Supplementation and Short-Course Radiotherapy Followed by Immunotherapy Combined With CAPEOX Neoadjuvant Therapy in Locally Advanced Rectal Cancer
This study is a prospective phase II clinical trial aimed at exploring the potential benefits of supplementing β-hydroxybutyrate with existing short course radiotherapy sequential immunotherapy and CAPEOX therapy.
开始日期2026-01-01 |
申办/合作机构- |
100 项与 卡培他滨 相关的临床结果
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100 项与 卡培他滨 相关的转化医学
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100 项与 卡培他滨 相关的专利（医药）
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11,491
项与 卡培他滨 相关的文献（医药）2026-02-01·JOURNAL OF ONCOLOGY PHARMACY PRACTICE
Retrospective evaluation of adjuvant capecitabine dosing patterns in triple negative breast cancer
Article
作者: Yang, Heng ; Fleming, Gini F ; Chen, Nan ; Lin, Kun ; Hahn, Olwen ; Polley, Eric ; O’Donnell, Peter H ; Michaels, Elena ; Nanda, Rita ; Howard, Frederick M
Background:
The CREATE-X trial demonstrated that adjuvant capecitabine was effective in prolonging survival in high-risk triple-negative breast cancer (TNBC) patients. However, the recommended dose is generally not well tolerated by the US population. The goal of this study is to analyze dosing patterns in an ethnically diverse cohort to better characterize tolerability and inform future dosing guidelines.
Methods:
In our single-center retrospective study, we evaluated safety and tolerability in TNBC patients undergoing adjuvant capecitabine treatment. The primary endpoint, relative dose intensity (RDI) across eight cycles, was examined alongside subgroup analyses based on age, race, BMI, and initial dose. Secondary endpoints include capecitabine-related side effects and survival.
Results:
67 patients who completed adjuvant capecitabine at University of Chicago Medicine (UCM) between January 2017 and November 2022 were eligible. The mean RDI across eight cycles of treatment was 60.2% (95% CI: 0.554–0.650). When compared to the CREATE-X trial, the RDI in our population was significantly lower (0.602 vs. 0.787, p < 0.001). There was no statistically significant difference in average RDI across eight cycles for patients stratified by age, BMI, race, or initial starting dose. The most frequently reported adverse events were hand-foot syndrome (73%), diarrhea (27%), and fatigue (22%), consistent with prior studies.
Conclusions:
Our data demonstrates that a significant portion of patients have a lower tolerated dose of capecitabine in comparison to the recommended adjuvant dose. Acknowledging the limitations of our single-center analysis, RDI was not significantly affected by age, race, BMI, or initial starting dose.
2026-02-01·BREAST
Nivolumab in combination with ipilimumab versus capecitabine as post-operative treatment for triple negative breast cancer patients with residual disease after neoadjuvant chemotherapy: a multicentre, randomized, open-label phase II trial – BREASTIMMUNE-03
Article
作者: Jouannaud, Christelle ; Derbel, Olfa ; Spano, Jean-Philippe ; Doublet, Louis ; Molin, Yann ; Trédan, Olivier ; Heudel, Pierre-Etienne ; Bachelot, Thomas ; Viret, Frédéric ; Mansi, Laura ; Grenier, Julien ; Chabaud, Sylvie ; Petit, Thierry ; Ferrero, Jean Marc ; Toussaint, Philippe ; Garin, Gwenaële ; Pierga, Jean-Yves ; Robert, Aurélien ; Patsouris, Anne ; Levy, Christelle ; Pérol, David ; Loirat, Delphine ; Frenel, Jean Sébastien
BACKGROUND:
Triple negative breast cancer (TNBC) patients with residual disease after neoadjuvant chemotherapy (NAC) face high risk of recurrence. BREASTIMMUNE-03 trial evaluates the efficacy of nivolumab and ipilimumab combination compared to capecitabine as adjuvant treatment.
METHODS:
This multicentre, randomized open-label phase II trial included TNBC patients with Residual Cancer Burden (RCB) of class II-III after NAC and surgery, and allocated them to randomization (1:1) to receive nivolumab plus ipilimumab or capecitabine for 24 weeks. Randomization was stratified by center, ECOG performance status (PS) 0 or 1, and RCB Class. Primary endpoint was disease free survival (DFS), assessed in the intent-to-treat population. Safety analysis according to NCI-CTCAE V5.0 included all patients who received at least one dose of study drug.
RESULTS:
From July 2019 to October 2021, 95 patients were randomized to the nivolumab plus ipilimumab arm (NIVO + IPI n = 45), or to the capecitabine arm (CT n = 50). With a median follow-up of 34.3 (IQR 33-36) months, 39 events (relapse or death) were reported: 17 (38 %) for NIVO + IPI; 22 (44 %) for CT (HR 0.84, 95 %CI 0.45-1.59; log-rank test p-value 0.5938). 17 (38 %) patients in the NIVO + IPI arm prematurely discontinued treatment due to treatment-related adverse events (AEs), versus 7 (14 %) in the CT arm.
CONCLUSION:
A 6-month post-operative nivolumab plus ipilimumab treatment did not significantly improve DFS compared to capecitabine in TNBC patients with RCB II-III and resulted in increased immune-mediated AEs. Despite premature trial termination, our results do not support nivolumab plus ipilimumab adjuvant treatment in this setting.
TRIAL REGISTRATION:
NCT03818685.
2026-01-01·JOURNAL OF ETHNOPHARMACOLOGY
Multi-omics analysis reveals the mechanism of Cistanche deserticola against alcoholic liver disease via bile salt hydrolase and SCD1
Article
作者: Sun, Jiaxu ; Lu, Yingyuan ; Lei, Jun ; Yuan, Shuo ; Gao, Peng ; Jiang, Yong ; Fang, Xinlan ; Tu, Pengfei
ETHNOPHARMACOLOGICAL RELEVANCE:
Cistanche deserticola Y. C. Ma, revered as "desert ginseng" in traditional Chinese medicine, has been historically prescribed for treating five strains and seven injuries, and nourishing the five zang organs. While the total glycosides from C. deserticola (GCs) demonstrate hepatoprotective potential against acute alcoholic liver disease (ALD), their efficacy in chronic ALD and mechanism remain unexplored.
AIM OF THE STUDY:
This study aimed to investigate the protective effects of GCs against chronic ALD and to elucidate its molecular mechanisms by multi-omics approach.
MATERIALS AND METHODS:
A chronic ALD mouse model evaluated the therapeutic effects of GCs, with systematic assessment of hepatic pathological features including liver index, liver functions, and oxidative stress, etc. Integrated multi-omics strategies (plasma-targeted metabolomics, bile acid-specific profiling, hepatic transcriptomics) were employed to delineate metabolic reprogramming and identify critical signaling pathways. The BSH inhibitor caffeic acid phenethyl ester (CAPE) was used as a pharmacological tool for the mechanistic investigation of GCs. The molecular mechanism was validated by qRT-PCR, Western blot, and small interfering RNA (siRNA)-mediated gene silencing methods.
RESULTS:
GCs treatment significantly attenuated ALD pathologies. Plasma-targeted metabolomics and bile acid profiling demonstrated GCs-mediated remodeling of bile acid homeostasis and lipid metabolic networks. Mechanistically, GCs potently inhibited BSH activity, which was validated the pivotal role in ALD pathogenesis by CAPE. Transcriptomic and molecular analyses revealed that GCs subsequently reduced SCD1, and activated AMPK/mTOR signaling, thereby coordinately regulating lipid catabolism, and inflammatory cascades.
CONCLUSION:
These findings highlight the protective effects of GCs against chronic ALD through inhibition of BSH activity to dictate bile acid metabolism, thereby alleviating cholestasis, which subsequently regulate SCD1/AMPK/mTOR signaling pathway.
1,544
项与 卡培他滨 相关的新闻（医药）2025-12-12
·肿瘤界
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斑蝥酸钠维生素B6注射液临床应用专家共识
中国老年保健协会肺癌专业委员会
【摘要】 我国癌症防治形势严峻，尽管靶向治疗和免疫治疗取得了显著进展，化疗仍在综合治疗中占据基石地位，而其毒性反应是临床实践中不容忽视的挑战。斑蝥酸钠维生素B6注射液作为一种兼具抗肿瘤与减毒作用的复方制剂，在我国临床应用已逾二十年，但临床实践中对其应用尚缺乏统一规范。为此，中国老年保健协会肺癌专业委员会组织专家基于现有循证证据与临床经验制定了本共识。共识系统阐述了该制剂的药理机制、药代动力学特点，并针对其在肺癌、肝癌等多种恶性肿瘤中的临床应用提出了具体的推荐意见。本共识旨在为临床医生提供斑蝥酸钠维生素B6注射液的规范化用药指导，以促进其合理应用，最终改善肿瘤患者的疗效与生活质量。
【关键词】 斑蝥酸钠维生素B6注射液；专家共识；恶性肿瘤；临床应用
引用本文：中国老年保健协会肺癌专业委员会. 斑蝥酸钠维生素B6注射液临床应用专家共识. 中国肺癌杂志, 2025, 28(10): 727-737.
我国癌症防控面临严峻挑战，2022年新发恶性肿瘤病例数高达482.47万例，占全球总数的近1/4，癌症防治工作任重道远[1]。科学家不断探索，尝试采用各种手段和方法来攻克癌症。近二十年来，新的抗肿瘤治疗药物不断突破，但化疗作为经典的系统性治疗手段，仍发挥着不可替代的基石作用。
斑蝥酸钠维生素B6注射液是斑蝥酸钠与维生素B6组成的复方制剂。其中，斑蝥酸钠兼具抗肿瘤及改善放化疗毒副反应的作用，可增强患者免疫功能，提高生活质量；维生素B6则在预防和控制化疗所致轻、中度恶心呕吐等方面具有确切疗效且安全性良好。该制剂在我国临床应用已逾二十年，积累了一定规模的中国患者应用数据，然而，临床医生对现有研究数据的解读存在差异，导致在适用人群、治疗时机、用法用量及联合方案等方面实践不一，尚缺乏统一的临床应用指导。
为此，中国老年保健协会肺癌专业委员会组织相关领域专家，基于现有循证证据及临床实践经验，通过召开多次专家会议就斑蝥酸钠维生素B6注射液临床应用的关键问题进行了深入讨论，最终形成《斑蝥酸钠维生素B6注射液临床应用专家共识》，以期为临床肿瘤医生提供科学规范的用药指导，推动临床合理用药实践，从而助力提升患者临床疗效和生活质量。
1
共识编制方法及过程
1.1
检索策略
共识检索策略以“斑蝥酸钠维生素B6注射液”作为中英文检索词，检索中国知网、万方数据、中华医学期刊网、EMBASE、PubMed、The Cochrane Library等中英文数据库中的临床及基础研究。检索时间从建库截至2025年5月31日。
1.2
推荐意见的形成
本共识的推荐意见经由系统化的方法形成。首先，基于对循证证据的汇总与分析，采用GRADE体系对证据质量进行分级（A：高质量；B：中等质量；C：低质量）[2]。在此基础上，初步拟定了关于斑蝥酸钠维生素B6注射液临床应用的8条推荐意见，并明确了其推荐强度（I级推荐和II级推荐）。随后，通过专家问卷调查与共识会议对推荐内容进行多轮研讨论证，将共识度≥80%的条目纳入共识草案[3]。最终版本经过专家组反复评议与修订后定稿。
2
药理机制及药代动力学特点
2.1
药理机制
斑蝥酸钠维生素B6注射液是一种由斑蝥酸钠与维生素B6通过螯合作用形成的复方抗肿瘤制剂。通过斑蝥酸钠介导的多靶点抗肿瘤机制（包括诱导DNA损伤、阻滞细胞周期、凋亡通路激活等），并结合维生素B6的代谢调节以拮抗相关不良反应，共同构成了其治疗作用的基础[4,5]。
斑蝥酸钠在抑制肿瘤生长、减轻放化疗毒性反应方面具有明确疗效。其作用机制已得到系统阐述，主要包括：（1）抑制肿瘤细胞DNA与RNA合成，阻断核酸的代谢过程，同时限制氨基酸吸收，从而抑制肿瘤关键蛋白合成，诱导细胞凋亡，实现对肿瘤细胞的直接杀伤与增殖抑制；（2）激活巨噬细胞、淋巴细胞及多形核白细胞，促进白细胞介素（interleukin, IL）分泌，调控T淋巴细胞亚群比例，增强机体抗肿瘤免疫应答及对肿瘤细胞的清除能力；（3）诱导骨髓造血干细胞向粒-单核细胞系分化，加速白细胞成熟，进而有效提升外周血白细胞数量[4,6]；（4）具有一定的镇痛作用，可缓解肿瘤患者的癌性疼痛症状。近年来研究[7,8]进一步揭示，斑蝥酸钠能够刺激淋巴细胞产生IL-2，增强机体免疫功能；通过抑制IL-8，影响肿瘤新生血管生成，从而阻断肿瘤转移途径。维生素B6作为水溶性维生素，在氨基酸代谢中发挥重要作用，通过促进氨基酸脱羧转化为γ-氨基丁酸，抑制中枢神经系统兴奋，从而减轻化疗引起的恶心、呕吐反应。同时，维生素B6在维持白细胞正常水平、促进造血功能、改善贫血状态以及减轻化疗相关并发症方面亦具有积极效果。
综上，斑蝥酸钠维生素B6注射液通过多靶点、多途径的协同作用，在肿瘤化疗的辅助治疗中展现出重要临床应用价值。
2.2
药代动力学
目前关于斑蝥酸钠维生素B6注射液的药代动力学研究数据有限。
3
斑蝥酸钠维生素B6注射液的临床应用
3.1
斑蝥酸钠维生素B6注射液的用法用量
推荐意见1：联合方案。采用斑蝥酸钠维生素B6注射液30-50 mL，加0.9%氯化钠注射液或5%葡萄糖注射液250 mL，静脉滴注，每日1次（IA）。
推荐意见2：单药方案。采用斑蝥酸钠维生素B6注射液40 mL，加0.9%氯化钠注射液或5%葡萄糖注射液250 mL，静脉滴注，每日1次（IB）。
推荐意见3：灌注方案。胸腔注入斑蝥酸钠维生素B6注射液50 mL联合其他胸腔注入药物。灌注治疗期间常规治疗（IB）。
斑蝥酸钠维生素B6注射液为复方制剂，规格为10 mL，每次10-50 mL，以0.9%氯化钠注射液或5%葡萄糖注射液250-500 mL，适量稀释后静脉滴注，每日1次。斑蝥酸钠维生素B6注射液在不同治疗方案中的用法与用量，参见表1[7,9-46]。
3.2
肺癌中的临床应用
推荐意见4：对于接受系统化疗的非小细胞肺癌（non-small cell lung cancer, NSCLC）患者，推荐联合斑蝥酸钠维生素B6注射液（IB）。对于合并恶性胸腔积液（malignant pleural effusion, MPE）的NSCLC患者，推荐采用化疗联合斑蝥酸钠维生素B6注射液进行胸腔灌注，以增强局部控制（IB）。
晚期肺癌的治疗强调以全身性治疗为核心的多学科综合模式。近年来，在分子靶向治疗与免疫治疗的推动下，其治疗策略持续演进，患者生存结局得到明显改善。尽管如此，对于驱动基因阴性或处于特定治疗线数的患者而言，传统含铂双药化疗仍构成重要的治疗基础。在此背景下，斑蝥酸钠维生素B6注射液在联合治疗方案中展现出增强抗肿瘤疗效的作用，同时减轻放化疗相关的毒性反应，优化晚期NSCLC的治疗效果。
3.2.1 联合化疗
含铂双药化疗是我国晚期NSCLC的常用治疗方案，但常伴随一定的不良反应。多项研究讨论了在吉西他滨/铂类（GP方案）[7,9,10]、紫杉醇/铂类（TP方案）[13,14]、长春瑞滨/铂类（NP方案）[15-17]、多西他赛/铂类（DP方案）[18,19]、培美曲塞/铂类（AP方案）[20-22]等标准含铂双药方案基础上，联合应用斑蝥酸钠维生素B6注射液的效果。系列研究结果显示，联合斑蝥酸钠维生素B6注射液在缓解骨髓抑制、消化道反应等化疗相关毒性方面具有一定优势，并显示出改善患者生活质量和临床症状的趋势。
一项纳入19项随机对照试验的meta分析提供了较为综合的证据[4]，结果显示，与单纯化疗相比，化疗联合斑蝥酸钠维生素B6注射液在客观缓解率（objective response rate, ORR）（RR=1.58, 95%CI: 1.40-1.79）、卡氏体能状态（Karnofsky performance status, KPS）评分改善（RR=1.68, 95%CI: 1.42-1.99）、临床症状改善（RR=1.68, 95%CI: 1.44-1.96）等方面表现更优，同时降低了白细胞减少（RR=0.36, 95%CI: 0.27-0.49）、血小板较少（RR=0.46, 95%CI: 0.33-0.63）及呕吐（RR=0.50, 95%CI: 0.37-0.67）的发生风险。Cando-L1研究是一项开放标签、随机III期临床研究[47]，其初步报告显示，在表皮生长因子受体（epidermal growth factor receptor, EGFR）野生型或未知晚期/转移性NSCLC患者的二线治疗中，斑蝥酸钠维生素B6注射液联合多西他赛组患者的中位总生存期（overall survival, OS）显著优于多西他赛单药组（9.83 vs 5.03个月，P=0.035）。
3.2.2 胸腔灌注
MPE是晚期恶性肿瘤的常见并发症，系肿瘤细胞侵犯胸膜所致的胸膜腔积液。MPE几乎可发生于所有恶性肿瘤，其中肺癌是导致MPE最常见的病因[48]。《肺癌合并恶性胸腔积液诊疗专家共识》[48]建议将化疗药物或联合其他药物进行胸腔灌注治疗作为MPE管理的重要手段。
多项临床研究评估了斑蝥酸钠维生素B6注射液用于MPE局部灌注治疗的效果。研究[25,26]显示，斑蝥酸钠维生素B6注射液联合顺铂行胸腔灌注，可显著提高肺癌合并MPE患者的积液缓解率，改善生活质量。斑蝥酸钠维生素B6注射液联合洛铂胸腔灌注也观察到同样的获益[27]。
因此，斑蝥酸钠维生素B6注射液单药[49]或联合化疗药物[26,27,50]胸腔灌注对控制MPE更加明显、迅速，临床效果显著，可改善患者体能状态，胃肠道反应发生率更低，提升患者免疫力[50]，提高患者生活质量。
3.2.3 其他联合治疗
免疫检查点抑制剂（immune checkpoint inhibitors, ICIs）的应用为晚期驱动基因阴性NSCLC的治疗带来重大变革。斑蝥酸钠维生素B6注射液作为一种具有免疫调节作用的药物，可增强机体的抗肿瘤免疫应答。研究[51,52]表明，该药物与程序性细胞死亡受体1（programmed cell death 1, PD-1）抗体联合化疗方案，可降低肿瘤标志物水平，改善血清炎症因子谱，并有助于提升患者生活质量及体能状态，整体安全性良好。
放疗在晚期NSCLC中主要用于局部病灶控制与症状缓解，并可延缓耐药发生、降低远处转移风险。临床研究[24]表明，放疗期间联合应用斑蝥酸钠维生素B6注射液，有助于降低放射性肺炎及骨髓抑制的发生风险，并减轻放疗相关毒副反应。
目前，斑蝥酸钠维生素B6注射液在联合免疫治疗及放疗领域的研究证据仍相对有限，且多为观察性研究。因此，其在减轻放射性损伤、增强免疫治疗效果方面的具体作用机制及最佳应用模式，尚待更多大样本、前瞻性研究进一步验证。
3.3
原发性肝细胞癌（hepatocellular carcinoma, HCC）中的临床应用
推荐意见5：对于接受系统化疗的原发性HCC患者，推荐联合使用斑蝥酸钠维生素B6注射液（IB）。经导管动脉化疗栓塞术（transcatheter arterial chemoembolization, TACE）中，建议联合斑蝥酸钠维生素B6注射液（IB）。接受放疗的原发性HCC患者，可在放疗期间联合斑蝥酸钠维生素B6注射液（IIC）。晚期原发性HCC患者可以考虑接受斑蝥酸钠维生素B6注射液单药治疗（IIB）。
HCC的治疗策略强调多学科协作，综合运用手术、消融、介入、放疗及系统性抗肿瘤治疗等多种手段。体外研究[53]证实在4种HCC细胞系中，斑蝥酸钠维生素B6注射液可阻滞多种人HCC细胞周期进程，并促进细胞凋亡。因此，斑蝥酸钠维生素B6注射液与上述治疗方式联用，可增强抗肿瘤治疗效果，减轻其他治疗相关毒性，改善患者生活质量。
3.3.1 联合全身化疗
FOLFOX4方案在我国被批准用于不适合手术切除或局部治疗的局部晚期和转移性HCC的一线治疗方案[54]。一项斑蝥酸钠维生素B6注射液同步低剂量放疗序贯FOLFOX4方案治疗晚期HCC[34]，结果显示，患者中位OS为9.7个月，中位无进展生存期（progression-free survival, PFS）为5.9个月，其中单发巨块型患者的中位OS明显优于肝内多发转移患者，提示该联合方案能提高单纯FOLFOX4方案的疗效，且不良反应可控。蒋峰等[35]的研究进一步证实，在5-氟尿嘧啶+奥沙利铂方案基础上联合斑蝥酸钠维生素B6注射液，可显著延长患者生存时间。该研究将64例患者随机分组，结果显示，治疗组的24个月生存率达到50%，显著高于对照组的6.67%（P<0.05），提示联合用药有助于提高近期疗效并延长生存时间。同时，治疗组患者在生活质量和体能状态的改善方面也优于对照组。此外，斑蝥酸钠维生素B6注射液联合化疗还可改善HCC患者的免疫功能，具体表现为CD3+、CD4+ T细胞比例及CD4+/CD8+比值升高，并有助于改善患者临床症状、增加体重，效果均优于单纯化疗[30]。一项meta分析[55]结果显示，与单纯化疗或对症支持治疗相比，联合斑蝥酸钠维生素B6注射液可提高HCC患者的近期疗效与生活质量，并减轻化疗相关的胃肠道反应、骨髓抑制及肝功能损伤等不良反应。
3.3.2 联合TACE治疗
TACE是不可手术切除HCC最常用的局部治疗方法之一，具有微创、可重复等优点[54]。然而，TACE术后常出现恶心、呕吐、白细胞减少及肝功能损伤等不良反应[32]。研究显示，TACE术前[30]或术后[31,32]静脉滴注斑蝥酸钠维生素B6注射液，可以显著减轻患者恶心、呕吐等胃肠道反应。此外，在TACE术中，与化疗药物序贯使用斑蝥酸钠维生素B6注射液50-80 mL[28,29]，有助于减少化疗药物的毒副反应，并显示出延长生存时间、提高远期生存率的趋势。
索拉非尼是多靶点抗肿瘤药物，TACE联合索拉非尼是目前临床治疗HCC的常用策略。徐雪勤等[33]在此方案基础上加用斑蝥酸钠维生素B6注射液，结果显示，观察组患者血清肿瘤标志物高尔基体跨膜糖蛋白73（Golgi protein 73, GP73）、甲胎蛋白（alpha-fetoprotein, AFP）、糖类抗原 19-9（carbohydrate antigen 19-9, CA19-9）下降幅度更为显著，肝功能指标血清总胆红素（total bilirubin, TBiL）、谷丙转氨酶（alanine aminotransferase, ALT）和白蛋白（albumin, ALB）改善更优，安全性方面两组总体耐受性良好，表明三药联合可更有效抑制肿瘤进展、改善肝功能，且安全性良好。
一项meta分析[56]纳入7项随机对照试验共562例患者，分析结果进一步证实，斑蝥酸钠注射液联合TACE治疗HCC，相较单纯TACE，在提高治疗有效率、临床受益率及生存率方面均更具有优势。
3.3.3 联合放疗
斑蝥酸钠维生素B6注射液与放疗联用可发挥协调增效与减毒效应[36,57]。薄常文等[57]的研究显示，与单纯放疗相比，联合斑蝥酸钠维生素B6注射液可显著提高原发性HCC患者的ORR（80% vs 55.3%, P<0.05），并降低骨髓抑制发生率，表明联合方案在促进肿瘤消退、提高近期疗效的同时，还能有效保护骨髓功能。
刘建民等[36]针对中晚期HCC患者的研究进一步证实，斑蝥酸钠维生素B6注射液联合射波刀治疗，在近期疗效与生活质量改善方面均优于单纯射波刀治疗，且急性不良反应发生率更低，提示该联合方案有助于病情稳定、延缓疾病进展。此外，斑蝥酸钠维生素B6注射液联合微波消融术也显示出协同增效与减轻不良反应的作用[37]。
3.3.4 单药治疗
在单药应用方面，一项前瞻性单中心III期临床研究[38]证实，斑蝥酸钠维生素B6注射液可有效改善晚期HCC患者的临床症状与生活质量，并延长生存时间，同时展示出良好的安全性。
3.4
其他癌种的探索性应用
推荐意见6：对于常规治疗方案受限或疾病进展的晚期实体瘤及血液系统恶性肿瘤患者，可考虑参加斑蝥酸钠维生素B6注射液相关临床研究（IIC）。
斑蝥酸钠维生素B6注射液已用作多种消化系统肿瘤的抗肿瘤药物，例如胃癌[41,58,59]、结直肠癌[39-40,60]和贲门癌[61]。斑蝥酸钠维生素B6注射液联合XELOX方案给胃癌患者带来更好的治疗获益，同时减轻XELOX方案相关的白细胞减少、恶心和呕吐等不良反应[62]。同样，斑蝥酸钠维生素B6注射液联合FOLFOX方案治疗胃癌，能有效缓解单用FOLFOX方案引起的胃肠道反应和肝功能损伤[63]。一项对24项试验中1825例晚期消化系统肿瘤患者进行的荟萃分析[64]表明，与单纯常规药物治疗相比，联合斑蝥酸钠维生素B6注射液治疗在提高总体肿瘤缓解率、疾病控制率和体能状态方面更有效，同时能减轻化疗引起的不良反应。
对于非消化系统肿瘤，斑蝥酸钠维生素B6注射液在临床上常与化疗联用于乳腺癌[42-44]和卵巢癌[46]，或与放化疗联用于宫颈癌[65,66]和鼻咽癌[67,68]。临床前研究[69]表明，斑蝥酸钠能有效抑制乳腺癌细胞增殖、侵袭和迁移，通过磷脂酰肌醇3-激酶（phosphatidylinositol 3-kinase, PI3K）/蛋白激酶B（protein kinase B, AKT）/哺乳动物雷帕霉素靶蛋白（mammalian target of rapamycin, mTOR）通路诱导G0/G1期细胞周期停滞和凋亡。斑蝥酸钠不仅能抑制宫颈癌细胞生长，还能通过抑制蛋白酪氨酸磷酸酶非受体型1（protein tyrosine phosphatase non-receptor type 1, PTPN1）增强其对顺铂的敏感性[70]。斑蝥酸钠维生素B6注射液在临床上还与化疗联合用于治疗血液系统恶性肿瘤[71,72]。
目前对于斑蝥酸钠维生素B6注射液在这些癌种中的获益-风险特征，仍然缺乏全面的了解，有必要进行系统评价和荟萃分析，并为斑蝥酸钠维生素B6注射液在肿瘤治疗中的合理临床应用提供循证支持。
3.5
化疗所致白细胞减少症
推荐意见7：建议化疗时联合应用斑蝥酸钠维生素B6注射液，可改善化疗导致的骨髓抑制，降低白细胞减少发生率（IB）。
肿瘤化疗导致的白细胞减少是化疗常见的血液学不良反应和剂量限制性不良反应。白细胞降低的程度与使用化疗药物的种类和剂量有关。当使用5-氟尿嘧啶、吉西他滨、紫杉类等细胞周期特异性药物时，中性粒细胞计数的最低点通常见于给药后7-14 d，并于14-21 d逐渐恢复至正常值；当使用环磷酰胺、阿霉素等细胞周期非特异性药物时，中性粒细胞计数的最低点通常出现在给药后的10-14 d，于21-24 d逐渐恢复正常[73]。
两项meta分析[74,75]显示化疗联合斑蝥酸钠维生素B6注射液可有效降低白细胞减少发生率，改善患者一般状况。多项临床研究[14,43,72,76]结果表明斑蝥酸钠维生素B6注射液与包括细胞周期特异性药物（5-氟尿嘧啶、吉西他滨、紫杉类等）及细胞周期非特异性药物（环磷酰胺、阿霉素等）的化疗方案联合使用都可以有效减轻化疗导致的白细胞减少，提高患者生活质量。
4
不良反应及处理建议
推荐意见8：对于轻度的不良反应，如轻微的恶心、呕吐、发热等，可先采取对症治疗。同时，可适当调整药物剂量或用药频率，观察症状是否改善。如果出现中重度不良反应，应立即停药（IB）。
斑蝥酸钠维生素B6注射液常见不良反应包括恶心、呕吐、肌酐/尿素氮升高、发热及静脉炎等，但程度较轻，为中度或者轻度，且均经停药及对症处理后消失。一项真实世界研究纳入的960例患者中，有88例患者出现不良反应，其中26例出现A型恶心、呕吐，9例出现B型肝功能损伤，10例出现B型肾功能损伤，25例出现B型发热，18例出现A型静脉炎，所有患者经停药及对症处理后症状消失。药物引起的恶心呕吐在用药早期出现，一般无需特殊处理。由此可见斑蝥酸钠维生素B6注射液用于癌症治疗的不良反应程度较轻，安全性高[77]。
用药前做好患者教育，充分告知患者可能出现的不良反应，使患者对于不良反应有预期性准备。
5
总结
斑蝥酸钠维生素B6注射液在多种恶性肿瘤的临床治疗中显示出积极的疗效，在联合治疗中表现出独特优势，能有效减毒增效、改善患者生活质量，丰富了临床用药选择。共识制定本身即为一种推动肿瘤治疗规范化的重要方法论实践，通过系统梳理斑蝥酸钠维生素B6注射液的临床证据与实践经验，为斑蝥酸钠维生素B6注射液在临床的规范化应用提供指导，并期待未来开展更多高质量的临床研究，以进一步优化其在临床治疗中的应用策略。
编写委员会
主 编：
陈 军 天津医科大学总医院
潘宏铭 浙江大学邵逸夫医院
邬 麟 湖南省肿瘤医院
吴凤英 同济大学附属上海市肺科医院
执笔专家（按姓氏汉语拼音排序）：
李 昕 天津医科大学总医院
刘京豪 天津医科大学总医院
马 晴 天津医科大学总医院
韦 森 天津医科大学总医院
张洪兵 天津医科大学总医院
张文学 天津医科大学总医院
撰写小组专家（按姓氏汉语拼音排序）：
常香云 天津医科大学总医院
陈恩强 四川大学华西医院
郭克锋 黄河三门峡医院
郭占林 内蒙古医科大学附属医院
黄广慧 山东省立医院
贾军梅 山西医科大学第一医院
宋荣峰 江西省肿瘤医院
王 虹 兰州大学第二医院
王克强 天津医科大学总医院
邢培培 天津医科大学总医院
徐 燕 北京协和医院
杨立伟 河北医科大学第四医院
姚 颐 武汉大学人民医院
邹方文 中南大学湘雅二医院
参考文献
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来源：《中国肺癌杂志》官网
编辑：lagertha
审核：素问
2025-12-12
在消化系统恶性肿瘤的谱系中，胆管癌长期以来都是一个令临床医生和患者感到沉重的名词。这种起源于胆管上皮细胞的恶性肿瘤，因其解剖位置深在、起病隐匿、侵袭性强且预后极差，常被称为“沉默的杀手”。在过去很长一段时间里，相比于肺癌或乳腺癌的飞速进展，胆管癌的诊疗手段相对匮乏，晚期患者的五年生存率始终难以突破个位数的瓶颈。然而，流行病学数据的变化正在敲响警钟：这不再是一种可以被忽视的“罕见病”。
2025年12月10日，欧洲胆管癌研究网络牵头，联合全球35个国家的147位顶尖专家，在权威期刊《Nature Reviews Gastroenterology & Hepatology》上正式发表了题为《Cholangiocarcinoma 2026: status quo, unmet needs and priorities》的共识声明。这份文件不是普通的学术综述，而是基于德尔菲法达成的全球战略共识。它系统梳理了从流行病学、分子分型到临床治疗的全链条证据，明确了ICD-11分类标准的临床应用，确立了免疫联合化疗的一线地位，并为FGFR2、IDH1等靶点的精准治疗划定了标准路径。这份共识的发布，标志着全球医学界对胆管癌的认知从“单一疾病”向“分子异质性肿瘤群”的彻底转变，为未来五年的临床实践和科研方向提供了详尽的路线图[1]。
图1 胆管癌的解剖亚型及其最常见的基因改变
胆管癌全球发病率上升与“隐形”的威胁
从“罕见”走向“常见”
长期以来，胆管癌被定义为罕见肿瘤（发病率<6/10万），但这在很大程度上掩盖了其日益严峻的现实威胁。共识声明通过详实的全球数据指出，在过去二十年间，胆管癌的发病率和死亡率在世界范围内均呈现上升趋势。特别是在部分西方发达国家，这一趋势尤为显著。例如，英国的最新数据显示，肝内胆管癌（iCCA）的患病率已经与肝细胞癌（HCC）持平。这一数据极具冲击力，它颠覆了“肝癌主要是肝细胞癌”的传统认知，提示胆管癌正在演变为造成重大社会、健康和经济负担的公共卫生问题。专家分析，这种上升趋势一方面与肥胖、代谢综合征、脂肪肝等非病毒性风险因素的全球流行密切相关；另一方面，也反映了诊断技术的进步，使得过去常被误诊为“原发灶不明腺癌”的病例被正确归类。然而，共识也强调，由于全球癌症编码系统的差异（ICD-10与ICD-11的混用），目前的统计数据可能仍低估了胆管癌的真实死亡负担，其导致的癌症相关死亡约占所有癌症死亡的2%[1]。
起病隐匿与早期诊断的“至暗时刻”
胆管癌最棘手的临床特征在于其生物学行为的“静默性”。肿瘤生长于复杂的胆管树系统内，早期往往没有任何特异性症状。当患者出现无痛性黄疸（皮肤巩膜黄染）、不明原因的体重减轻、陶土样便或腹痛时，肿瘤通常已经侵犯了肝门部的重要血管或发生了远处转移。临床数据显示，仅有20%至30%的新诊断患者在确诊时处于早期，拥有通过手术切除获得治愈的机会。对于绝大多数晚期患者而言，现有的治疗手段更多是姑息性的。这种“发现即晚期”的现状，根源在于缺乏针对普通人群或高危人群（如原发性硬化性胆管炎PSC患者）的有效筛查工具。传统的血清肿瘤标志物如CA19-9，虽然在临床广泛使用，但其敏感性和特异性均不理想，容易受到胆管炎、胆汁淤积等良性疾病的干扰，导致假阳性结果，无法作为早期筛查的可靠依据。
临床未满足需求与治疗响应的异质性
即便是在确诊之后，临床医生仍面临着巨大的决策挑战。胆管癌的高度异质性导致了治疗响应的极端差异。同样的标准化疗方案（如吉西他滨联合顺铂），在部分患者身上能维持数月的疾病稳定，而在另一部分患者身上却毫无波澜，肿瘤迅速进展。这种“同病不同命”的现象，长期以来缺乏精准的生物标志物来解释。此外，胆管癌的解剖位置特殊，取样极为困难，尤其是肝门部和远端胆管癌，往往只能通过内镜逆行胰胆管造影（ERCP）获取少量的细胞刷检样本。这些样本往往细胞量少、破碎严重，难以满足传统病理诊断和日益增长的分子检测需求。如何从有限的样本中获取最大的生物学信息，是当前临床亟待解决的核心痛点。
图2 全球胆管癌死亡率
基于德尔菲法的全球智慧结晶
跨越国界的顶级专家阵容
本共识声明的权威性源于其制定过程的严谨性和参与人员的广泛代表性。欧洲胆管癌研究网络作为核心发起方，联合了来自欧洲、北美、拉丁美洲、亚洲、非洲和大洋洲等35个国家和地区的147位顶尖专家。这一专家阵容涵盖了肿瘤内科、肝胆外科、肝病学、胃肠病学、病理学、基础转化科学以及放射学等多个学科，确保了视角的全面性。特别值得一提的是，共识制定过程还纳入了患者权益代表（如Cholangiocarcinoma Foundation和AMMF），这在顶级学术共识中并不多见，体现了以患者为中心的理念，确保最终的推荐意见不仅具有学术高度，也能切实反映患者的真实诉求和生活质量考量。
系统性证据合成与共识达成机制
为了确保结论的科学性，研究团队采用了改良的德尔菲法进行共识构建。首先，核心工作组对2020年至2025年间发表在PubMed等权威数据库上的数千篇相关文献进行了系统性的检索和筛选。检索关键词覆盖了流行病学、风险因素、分类、诊断、分期、遗传学、信号通路、代谢、肿瘤微环境、免疫学、生物标志物、内镜、手术及临床试验等全维度领域。基于海量的文献证据，核心组起草了包含59个关键问题的问卷。随后，这147位专家对问卷进行了独立的批判性评估和投票。通过多轮的意见征询和反馈修正，最终在绝大多数关键问题上达成了高度一致（大多数条款的同意率超过90%，部分甚至达到100%）。这种基于大数据的证据合成与专家经验的有机结合，使得该共识声明成为了当前胆管癌领域最权威的指导性文件[1]。
图3 胆管癌的危险因素
CD-11分类与分子图谱的深度融合
ICD-11分类系统的全面采纳：解剖学定义的标准化
共识声明中最具基础性但影响深远的创新之一，是对世界卫生组织最新批准的ICD-11分类系统的全面采纳和推广。在过去，胆管癌的分类较为混乱，常常与肝细胞癌或胆囊癌混淆，导致临床试验的入组标准不一，数据难以横向比较。新的ICD-11标准明确将胆管癌按解剖起源严格划分为三大类：肝内胆管癌（iCCA）、肝门部胆管癌（pCCA）和远端胆管癌（dCCA）。iCCA起源于二级胆管近端的肝内胆管系统；pCCA起源于左右肝管汇合处至胆囊管开口处；dCCA则起源于胆囊管开口至壶腹部。这种分类不仅仅是名称的规范，更是治疗策略的分水岭。研究表明，这三种亚型在分子背景、临床表现和预后上存在显著差异。例如，iCCA更常表现为肿块型，且富含FGFR2融合突变；而pCCA和dCCA则更多表现为沿胆管壁的浸润性生长，手术难度极大且分子靶点相对匮乏。ICD-11的推广为全球胆管癌数据的标准化收集和精准研究奠定了坚实的解剖学基础。
从组织学到分子图谱：诊疗逻辑的根本转变
共识明确提出，单纯依赖组织形态学的诊断已不足以指导现代胆管癌的治疗。我们必须从“显微镜时代”跨入“测序时代”，在确诊时同步进行全面的分子图谱分析。这标志着胆管癌诊疗逻辑的根本性转变。通过二代测序技术，临床医生可以识别出隐藏在肿瘤内部的关键驱动基因，如FGFR2融合/重排、IDH1/2突变、BRAF V600E突变、HER2扩增以及NTRK融合等。这些分子特征不再是冷冰冰的数据，而是连接患者与特效靶向药物的“密钥”。共识建议，对于所有晚期或不可切除的胆管癌患者，应常规进行多基因Panel检测。这不仅有助于发现潜在的治疗靶点，还能识别出微卫星高度不稳定或高肿瘤突变负荷的患者，从而指导免疫治疗的使用。
液体活检：突破取样难的物理瓶颈
针对胆管癌深在体内、取样极为困难的临床痛点，共识重点推荐了液体活检技术的应用。当组织样本不足以进行NGS检测，或患者身体状况无法耐受再次活检时，血液中的循环肿瘤DNA（ctDNA）成为了极佳的替代品。ctDNA不仅能无创地反映肿瘤的基因组特征，用于检测FGFR2、IDH1等可成药靶点，更具备动态监测的优势。在治疗过程中，通过连续监测ctDNA的丰度变化和新突变的出现，医生可以实时追踪肿瘤的克隆演化，提前发现耐药机制（如FGFR2激酶域的继发突变），从而在影像学进展之前及时调整治疗方案。液体活检的引入，为胆管癌的全程管理提供了一个无创、实时、动态的分子视窗[1]。
图4 CCA 肿瘤中的信号通路和分子改变及其相关靶向治疗
基于证据的治疗标准与生存获益
外科手术与辅助治疗：治愈的基石
尽管药物研发进展迅速，共识依然重申，R0手术切除（切缘阴性）仍是目前胆管癌患者获得长期生存乃至治愈的唯一途径。对于可切除的患者，术后推荐使用卡培他滨进行为期6个月的辅助化疗。这一推荐基于BILCAP大型III期临床试验的结果，数据显示辅助化疗能显著延长患者的总生存期，确立了其作为术后标准治疗的地位。此外，共识对肝移植在胆管癌中的应用给予了审慎但积极的评价。对于部分符合严格筛选标准（如肿瘤直径小于2cm的单发iCCA，或经过新辅助放化疗降期的pCCA）的患者，肝移植被确立为一种潜在的治愈性选项，其5年生存率在特定中心可达50%以上，为那些肿瘤局限但因解剖位置无法切除的患者开辟了新的生命通道。
晚期一线治疗：免疫联合化疗的确立
在晚期胆管癌的一线治疗领域，共识确认了TOPAZ-1研究带来的里程碑式进展，确立了“吉西他滨+顺铂+度伐利尤单抗”的新标准方案。长期以来，晚期胆管癌的一线治疗仅限于吉西他滨联合顺铂的化疗方案，生存获益处于瓶颈期。TOPAZ-1研究证实，在化疗基础上联合PD-L1抑制剂度伐利尤单抗，可以显著降低患者的死亡风险，且长期生存获益明显（2年生存率显著提升）。这一结果标志着胆管癌正式跨入了免疫治疗时代。共识还指出，另一种PD-1抑制剂帕博利珠单抗联合化疗（KEYNOTE-966研究）也取得了类似的阳性结果，进一步夯实了“免疫+化疗”作为晚期一线标准治疗的地位[2]。
靶向治疗：精准打击的临床数据
共识详细列出了基于分子特征的二线及后线治疗推荐，这些基于生物标志物的精准疗法展现了令人振奋的疗效数据：
FGFR2融合/重排：约10-15%的iCCA患者携带此变异。推荐使用FGFR抑制剂（如Pemigatinib, Futibatinib）。这类药物在经治患者中展现出了高达35%-40%的客观缓解率（ORR），且疾病控制时间显著长于传统二线化疗。
IDH1突变：约13-20%的iCCA患者携带此突变。推荐使用Ivosidenib，ClarIDHy研究显示其可显著改善无进展生存期（PFS），并具有良好的耐受性。
BRAF V600E突变：尽管发生率较低（约3-5%），但双靶向治疗显示出卓越疗效，ORR可达47%。
HER2过表达/扩增：随着抗体偶联药物（ADC）如T-DXd（德曲妥珠单抗）的兴起，HER2阳性胆管癌患者也迎来了新的治疗选择，初步数据显示了良好的抗肿瘤活性。 这些核心指标充分证明，胆管癌的治疗正在从“一刀切”的经验医学转向“量体裁衣”的精准医学[3]。
图5 胆管癌的临床决策和管理
肿瘤微环境与耐药的生物学根源
肿瘤微环境的“堡垒”效应与结缔组织增生
共识深入剖析了胆管癌难治的生物学根源——其独特的肿瘤微环境。胆管癌最显著的病理特征之一是强烈的结缔组织增生。肿瘤细胞通过分泌多种细胞因子（如TGF-β, PDGF），招募并激活大量的肿瘤相关成纤维细胞（CAFs）。这些CAFs分泌致密的胶原蛋白和其他细胞外基质成分，在肿瘤周围构建了一座坚硬的物理“堡垒”。这层屏障不仅导致肿瘤内部流体静水压升高，阻碍了化疗药物从血管渗透到肿瘤核心，还限制了免疫效应细胞（特别是CD8+T细胞）的浸润，形成了所谓的“免疫排斥”表型。这种机制解释了为何单纯化疗在胆管癌中往往效果有限，也指明了未来通过靶向基质（如抑制CAFs活性或降解基质）来增效治疗的新方向。
免疫生物学的“冷热”二元论
研究揭示，胆管癌在免疫学特征上表现出高度的异质性。绝大多数胆管癌属于“冷肿瘤”，其微环境中缺乏T细胞浸润，且充斥着免疫抑制性细胞（如M2型巨噬细胞、调节性T细胞Tregs）。这类肿瘤对单一的免疫检查点抑制剂反应极差。然而，约5-10%的患者表现为微卫星高度不稳定或高肿瘤突变负荷，这类肿瘤被称为“热肿瘤”，由于存在大量新抗原，对PD-1抗体响应极佳。共识指出，目前的科研热点在于如何将“冷肿瘤”转化为“热肿瘤”。机制研究表明，化疗药物（如吉西他滨）不仅能杀伤肿瘤细胞，还能诱导免疫原性细胞死亡，释放肿瘤抗原；而抗血管生成药物（如仑伐替尼）可以正常化肿瘤血管，改善T细胞的浸润。这正是GemCis+免疫联合方案以及“靶向+免疫”联合策略成功的理论基石。
代谢重编程与肿瘤干性的维持
胆管癌细胞展现出惊人的代谢适应性，这是其在恶劣微环境中生存并发生转移的关键。为了在缺氧、营养匮乏的微环境中生长，胆管癌细胞会发生代谢重编程，如增强糖酵解和谷氨酰胺代谢。此外，共识特别关注了肿瘤干细胞（CSCs）在胆管癌复发和耐药中的作用。CSCs是一小群具有自我更新和多向分化潜能的细胞，它们对传统化疗天然耐药，是肿瘤复发的“种子”。有趣的是，针对IDH1突变的靶向药物，其作用机制并非直接杀伤细胞，而是通过产生2-HG代谢产物，改变表观遗传修饰，诱导肿瘤细胞分化，从而剥夺其“干性”，抑制肿瘤生长。这一机制的阐明，为非细胞毒性治疗策略提供了强有力的生物学证据。
全生命周期的管理与社会意义
临床诊疗流程的重塑与MDT模式
这份共识声明对临床实践的指导意义是具体的、可操作的。它要求临床医生彻底改变传统的诊疗习惯。在诊断端，必须确立“无基因检测，不制定方案”的原则，特别是对于晚期患者，NGS检测应成为标准动作。在治疗端，应摒弃单一化疗的思维定势，全面评估免疫联合及靶向治疗的可能性。在管理端，共识强烈推荐多学科团队（MDT）协作模式。胆管癌的治疗涉及外科、肿瘤内科、放疗科、介入科、病理科和影像科等多个学科，只有通过MDT讨论，才能为患者制定出涵盖手术、消融、栓塞、系统治疗的最佳综合治疗方案，避免单科作战带来的治疗不足或过度治疗。
人工智能与数字病理的集成应用
展望未来，人工智能将在胆管癌的精准诊疗中扮演核心角色。共识提到，利用深度学习算法分析常规的H&E染色病理切片（数字病理学）和CT/MRI影像数据（影像组学），可以挖掘出人眼无法识别的亚视觉特征。这些AI模型有望在不进行昂贵测序的情况下，无创预测肿瘤的分子亚型（如预测FGFR2融合概率）、PD-L1表达水平甚至患者的预后。这种“虚拟活检”技术一旦成熟并临床转化，将极大地降低检测成本，提高诊疗效率，特别是在医疗资源相对匮乏的地区具有巨大的应用潜力。
局限性与全球健康公平
尽管前景光明，共识也冷静地指出了当前面临的局限与挑战。首先是医疗资源的不均衡，昂贵的NGS检测和新型靶向药物在低收入和中等收入国家难以普及，造成了新的全球医疗不公平。其次是耐药难题，靶向药物使用后不可避免会出现继发耐药（如FGFR2激酶域的点突变），亟需开发新一代克服耐药的抑制剂。此外，目前大多数高质量临床数据来自欧美人群，而亚洲人群（尤其是乙肝病毒相关或肝吸虫相关的胆管癌）的分子特征与欧美人群存在差异，现有的数据可能无法完全外推，需要更多基于亚洲人群的区域性研究验证。
未来展望与社会意义
共识最后提出了未来的优先事项：建立跨国界的胆管癌临床数据共享平台，打破数据孤岛；重点研发基于血液、尿液或胆汁的早期诊断标志物，实现早筛早诊；探索针对KRAS G12D、TP53等“不可成药”靶点的创新疗法，以及CAR-T等细胞治疗在实体瘤中的应用。对于社会公众而言，这份共识传递了积极的信号：胆管癌正在从一种“绝症”转变为一种可防、可控、甚至部分可治的慢性病。通过科学的分类、精准的检测和创新的疗法，我们正在逐步剥开胆管癌坚硬的外壳。这不仅是医学技术的进步，更是对每一个生命尊严的捍卫。
参考资料
[1]Banales, J.M., Rodrigues, P.M., Braconi, C. et al. Cholangiocarcinoma 2026: status quo, unmet needs and priorities. Nat Rev Gastroenterol Hepatol (2025).
[2]Oh, D.Y. et al. Durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer. NEJM Evid. 1, EVIDoa2200015 (2022).
[3]Lamarca, A. et al. Molecular targeted therapies: ready for "prime time" in biliary tract cancer. J. Hepatol. 73, 170–185 (2020).
文章由麦基洗德生物工程有限公司研发中心专家团队基于国际权威期刊新近发表的文献进行客观分析解读，旨在促进学术交流与行业洞察。文中引用的图表、数据均来自原始文献，版权归原作者及出版方所有。如涉及版权问题，请及时联系我们，我们将第一时间处理。
2025-12-12
The Phase 3 STAR-221 study evaluating a domvanalimab-based combination in upper gastrointestinal cancers will be discontinued due to futility Arcus is continuing to expand its development program for casdatifan, a potential best-in-class HIF-2a inhibitor with robust single-agent activity, and multiple data readouts are expected in 2026 Arcus’s early development efforts will focus on five programs targeting inflammatory and autoimmune (I&I) diseases; a small molecule targeting MRGPRX2 is expected to enter the clinic in 2026 With approximately $1B of cash and investmentsi, Arcus expects to be able to fund its planned operations until at least the second half of 2028
HAYWARD, Calif.--(BUSINESS WIRE)-- Arcus Biosciences, Inc. (NYSE:RCUS), a clinical-stage, global biopharmaceutical company focused on developing differentiated molecules and combination therapies for patients with cancer, inflammatory and autoimmune diseases, today announced the discontinuation of the Phase 3 STAR-221 study, being conducted in partnership with Gilead Sciences, Inc., due to futility. The decision is based on the recommendation from the Independent Data Monitoring Committee (IDMC) following its review of data from an event-driven, pre-specified interim analysis of overall survival (OS).
STAR-221 evaluated the anti-TIGIT antibody domvanalimab plus anti-PD-1 antibody zimberelimab and chemotherapy versus nivolumab plus chemotherapy as a first-line treatment for advanced gastric and esophageal cancers. At the interim analysis, the domvanalimab-based combination did not improve OS relative to that of nivolumab plus chemotherapy. The safety profile for the domvanalimab-based combination was similar to that of nivolumab plus chemotherapy, and there were no new safety findings identified.
“Patients in the domvanalimab-containing arm derived the same benefit as patients treated in the control arm, and there were no new safety concerns,” said Richard Markus, MD, chief medical officer at Arcus. “We are disappointed with this outcome and sincerely thank all those who participated in the study and made this research possible. We remain committed to advancing research for people living with cancer and immune-related diseases.”
The STAR-221 and the Phase 2 EDGE-Gastric studies will be discontinued, and Arcus and Gilead are communicating with investigators to determine appropriate next steps for patients in the study in addition to conducting a detailed analysis to better understand these results.
Future Direction
Arcus’s R&D investment and resources will focus on casdatifan, a potential best-in-class HIF-2a inhibitor, and its emerging small molecule I&I programs.
“The results from STAR-221 are not what we had hoped for, and we have important work ahead to meet the needs of patients on our domvanalimab studies and also accelerate the casdatifan and I&I programs,” said Terry Rosen, chief executive officer of Arcus. “We are fortunate to be well capitalized and plan to focus our resources on casdatifan, including studying new early-line combinations in kidney cancer, broadening its development into new tumor types, and extending our capabilities beyond oncology.”
Casdatifan targets a validated mechanism of action and has shown robust single-agent activity based on data reported from more than 120 patients with late-line clear cell renal cell carcinoma (ccRCC) in the ARC-20 Phase 1/1b clinical study. Those data have shown improvement on every efficacy measure evaluated, including overall response rate and progression-free survival (PFS), relative to reported data for the only marketed HIF-2a inhibitor. Arcus owns all of the rights to casdatifan outside of Japan and certain other Asian territories, which were optioned by Taiho Pharmaceutical Co., Ltd. in October 2025.
Arcus is focused on rapidly developing casdatifan in both immunotherapy (IO)-experienced and first-line metastatic ccRCC, anditsclinical investment in 2026 and 2027 will be primarily focused on maximizing the potential of casdatifan. The casdatifan program is expected to have multiple data readouts and cohort and study initiations in 2026 including:
Early 2026: Additional analyses from the ARC-20 cohorts evaluating casdatifan monotherapy in late-line ccRCC, including updated PFS data for the 100mg once-daily (QD) cohort, which utilizes the selected Phase 3 dose and formulation. Mid-2026: More mature data from the ARC-20 cohort evaluating casdatifan plus cabozantinib in the IO-experienced setting. This is the same setting and combination being evaluated in the ongoing Phase 3 PEAK-1 study. 2H 2026: Initial data from one or more ARC-20 cohorts evaluating casdatifan in early-line settings, as well as a go-no-go decision on the Phase 3 portion of eVOLVE-RCC02. Late 2026: Potential initiation of a Phase 3 registrational study in an early-line or first-line ccRCC setting.
Arcus's oncology portfolio also includes quemliclustat, a small-molecule CD73 inhibitor that completed enrollment of PRISM-1, the Phase 3 study in pancreatic cancer, earlier this year. Results are expected in 2027 for the registrational study, which is evaluating quemliclustat plus gemcitabine/nab-paclitaxel versus gemcitabine/nab-paclitaxel in first-line metastatic pancreatic ductal adenocarcinoma.
Arcus’s I&I portfolio includes several oral, small molecules being developed in indications currently dominated by injectable drugs. The portfolio includes the following programs: MRGPRX2, TNF, CCR6, CD89 and CD40L. Arcus expects to advance two potentially best-in-class small molecule inhibitors into the clinic in the timeframes noted below:
2026: MRGPRX2, a potential treatment for atopic dermatitis and chronic spontaneous urticaria; and Late 2026 - early 2027: TNF, a potential treatment for rheumatoid arthritis, psoriasis and inflammatory bowel disease (such as ulcerative colitis).
Domvanalimab, zimberelimab and quemliclustat are investigational molecules, and neither Arcus nor Gilead has received approval from any regulatory authority for any use globally, and their safety and efficacy have not been established. Casdatifan is also an investigational molecule, and Arcus has not received approval from any regulatory authority for any use globally, and its safety and efficacy have not been established.
About RCC
According to the American Cancer Society, kidney cancer is among the top 10 most commonly diagnosed forms of cancer among both men and women in the U.S., and an estimated 80,980 Americans will be diagnosed with kidney cancer in 2025. Clear cell RCC is the most common type of kidney cancer in adults. If detected in its early stages, the five-year survival rate for RCC is high; for patients with advanced or late-stage metastatic RCC, however, the five-year survival rate is only 18%. In 2022, approximately 32,200 patients with advanced kidney cancer required systemic therapy in the U.S., with over 20,000 patients receiving first-line treatment.
About Casdatifan (AB521)
Casdatifan is a small-molecule inhibitor of HIF-2a, a master switch that turns on hundreds of genes in response to low oxygen levels. In a majority of people with the most common form of kidney cancer (clear cell renal cell carcinoma), genetic anomalies result in the misregulation of this master switch and transformation of normal kidney cells into cancerous ones. Casdatifan was designed to provide deep and durable inhibition of the HIF-2a pathway. Early clinical studies have shown high response rates and a low primary progression rate relative to clinical benchmarks, warranting further investigation in late-stage studies. Casdatifan, which is administered in pill form once daily, has a safety profile that allows it to be investigated in combination with other treatments.
About Gastric and Esophageal Cancer
According to the World Health Organization, gastric cancer and esophageal cancer are the fifth and seventh leading causes of cancer deaths globally, accounting for more than 1.1 million cancer deaths each year. More than one-third of patients are diagnosed at an advanced stage, when five-year survival rates are only 5-7%.
About the STAR-221 Study
The STAR-221 study is a global, randomized, open-label, Phase 3 trial evaluating domvanalimab plus zimberelimab and chemotherapy versus nivolumab plus chemotherapy as a first-line treatment in locally advanced, unresectable or metastatic HER-2 negative gastric, gastroesophageal junction and esophageal adenocarcinomas. The study enrolled 1,040 patients from nearly 30 countries and participants were randomized 1:1 between two arms:
1600mg of domvanalimab intravenously (IV) every four weeks plus 480mg of zimberelimab IV every four weeks plus FOLFOX (oxaliplatin, leucovorin, fluorouracil) every two weeks or 1200mg of domvanalimab plus 360mg of zimberelimab every three weeks plus CAPOX (capecitabine and oxaliplatin) every three weeks. 240mg of nivolumab IV every two weeks plus FOLFOX every two weeks or 360mg of nivolumab plus CAPOX every three weeks.
The primary endpoints of the study are overall survival in PD-L1-high tumors (TAP ≥5%), PD-L1-positive tumors (TAP ≥1%) and in the intent-to-treat population (all PD-L1 levels), as assessed by central PD-L1 testing based on Tumor Area Positivity (TAP) score. Key secondary endpoints include progression-free survival (PFS) and patient-reported outcomes (PROs). Secondary endpoints include objective response rate (ORR), duration of response (DOR) and safety.
Taiho Pharmaceutical has development and commercial rights in Japan and other countries in Asia, excluding China, for domvanalimab and zimberelimab, and is conducting the ongoing STAR-221 Phase 3 registrational study in Japan.
More information about STAR-221 is available at ClinicalTrials.gov: NCT05568095.
About Domvanalimab
Domvanalimab is the first and most clinically advanced Fc-silent investigational monoclonal antibody that is specifically designed with Fc-silent properties to bind and block to the T-cell immunoreceptor with Ig and ITIM domains (TIGIT), a checkpoint receptor on immune cells that acts as a brake on the anticancer immune response. By binding to TIGIT with Fc-silent properties, domvanalimab is believed to work by freeing up immune-activating pathways and activating immune cells to attack and kill cancer cells without depleting the peripheral regulatory T cells important in avoiding immune-related toxicity. Combined inhibition of both TIGIT and programmed cell death protein-1 (PD-1) is believed to significantly enhance immune cell activation, as these checkpoint receptors play distinct, complementary roles in anti-tumor activity.
About Zimberelimab
Zimberelimab is an anti-programmed cell death protein-1 (PD-1) monoclonal antibody that binds PD-1, with the goal of restoring the antitumor activity of T cells. Zimberelimab has demonstrated high affinity, selectivity and potency in various tumor types. Zimberelimab is being evaluated in the U.S. and globally as a foundational anti-PD-1 treatment option in multiple ongoing clinical studies in combination with other immunotherapies. Guangzhou Gloria Biosciences Co. Ltd., which holds commercialization rights for zimberelimab in greater China, has obtained approval for zimberelimab for the treatment of recurrent or metastatic cervical cancer and for relapsed or refractory classical Hodgkin’s lymphoma. Zimberelimab is not approved for any use in the U.S. or other regions outside of China. Gloria conducts its development and commercialization activities independent of Arcus and Gilead.
About Arcus Biosciences
Arcus Biosciences is a clinical-stage, global biopharmaceutical company focused on developing differentiated molecules and combination therapies for patients with cancer, inflammatory and autoimmune diseases. In partnership with industry collaborators, patients and physicians around the world, Arcus is expediting the development of its late-stage portfolio of first- and/or best-in-class medicines against well-characterized biological targets and pathways and studying novel, biology-driven combinations that have the potential to help people with cancer live longer. Founded in 2015, the company has advanced multiple investigational medicines into registrational clinical trials including casdatifan, a HIF-2a inhibitor for clear cell renal cell carcinoma, and quemliclustat, a small-molecule CD73 inhibitor for pancreatic cancer. For more information about Arcus Biosciences’ clinical and preclinical programs, please visit www.arcusbio.com.
Important Information Regarding Data Comparisons
This press release includes comparisons between data for casdatifan from our Phase 1/1b ARC-20 trial and published data from separate trials that are not head-to-head studies. Cross-trial comparisons should be interpreted with caution due to differences in study populations, sample sizes, inclusion and exclusion criteria, trial design, and other factors that may limit direct comparability.
Forward Looking Statement
This press release contains forward-looking statements. All statements regarding events or results to occur in the future contained herein are forward-looking statements reflecting the current beliefs and expectations of management made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, including, but not limited to, changes in the company’s go-forward strategy, operating plans and allocation of resources; the company’s anticipated cash runway; the timing of future data readouts and study initiations, including for its MRGPRX2 inhibitor; and the advancement of the company’s early discovery portfolio. All forward-looking statements involve known and unknown risks and uncertainties and other important factors that may cause Arcus’s actual results, performance or achievements to differ significantly from those expressed or implied by the forward-looking statements. Factors that could cause or contribute to such differences include, but are not limited to: further changes to the company’s strategy and operating plans; risks associated with preliminary and interim data not being guarantees that future data will be similar; the unexpected emergence of adverse events or other undesirable side effects in Arcus’s investigational products, including casdatifan; difficulties or delays in initiating or conducting clinical trials due to difficulties or delays in the regulatory process, enrolling subjects or manufacturing or supplying product for such clinical trials; changes in the competitive landscape for Arcus’s programs; and the inherent uncertainty associated with pharmaceutical product development and clinical trials. Risks and uncertainties facing Arcus are described more fully in the “Risk Factors” section of Arcus’s most recent periodic report filed with the U.S. Securities and Exchange Commission. You are cautioned not to place undue reliance on the forward-looking statements, which speak only as of the date of this press release. Arcus disclaims any obligation or undertaking to update, supplement or revise any forward-looking statements contained in this press release except to the extent required by law.
i Based on cash, cash equivalents and marketable securities balance of $841 million as of September 30, 2025 and net proceeds of approximately $270 million from Arcus’s November 2025 financing.
Investor Inquiries: Pia Eaves VP of Investor Relations & Strategy (617) 459-2006 peaves@arcusbio.com Media Inquiries: Holli Kolkey VP of Corporate Affairs (650) 922-1269 hkolkey@arcusbio.com Maryam Bassiri AD, Corporate Communications (510) 406-8520 mbassiri@arcusbio.com
临床3期临床结果临床2期免疫疗法上市批准
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| 适应症 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|
| 胃食管交界处癌 | 美国 | 2022-12-14 | |
| 胰腺癌 | 美国 | 2022-12-14 | |
| 直肠癌 | 日本 | 2016-09-19 | |
| 食管癌 | 澳大利亚 | 2013-06-24 | |
| 局部晚期乳腺癌 | 欧盟 | 2012-04-20 | |
| 局部晚期乳腺癌 | 欧盟 | 2012-04-20 | |
| 局部晚期乳腺癌 | 欧盟 | 2012-04-20 | |
| 局部晚期乳腺癌 | 冰岛 | 2012-04-20 | |
| 局部晚期乳腺癌 | 冰岛 | 2012-04-20 | |
| 局部晚期乳腺癌 | 冰岛 | 2012-04-20 | |
| 局部晚期乳腺癌 | 列支敦士登 | 2012-04-20 | |
| 局部晚期乳腺癌 | 列支敦士登 | 2012-04-20 | |
| 局部晚期乳腺癌 | 列支敦士登 | 2012-04-20 | |
| 局部晚期乳腺癌 | 挪威 | 2012-04-20 | |
| 局部晚期乳腺癌 | 挪威 | 2012-04-20 | |
| 局部晚期乳腺癌 | 挪威 | 2012-04-20 | |
| 胃癌 | 中国 | 2008-10-17 | |
| 复发性乳腺癌 | 日本 | 2007-12-12 | |
| 结肠癌 | 日本 | 2003-04-30 | |
| 晚期胃癌 | 欧盟 | 2001-02-02 |
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| 适应症 | 最高研发状态 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|---|
| ER阳性/HER2阴性乳腺癌 | 临床3期 | 法国 | 2020-06-11 | |
| GRPR阳性/ER阳性/HER2阴性乳腺癌 | 临床3期 | 法国 | 2020-06-11 | |
| 肝转移 | 临床3期 | 法国 | 2020-06-11 | |
| 转移性胃腺癌 | 临床3期 | 美国 | 2015-01-20 | |
| 转移性胃腺癌 | 临床3期 | 日本 | 2015-01-20 | |
| 转移性胃腺癌 | 临床3期 | 阿根廷 | 2015-01-20 | |
| 转移性胃腺癌 | 临床3期 | 比利时 | 2015-01-20 | |
| 转移性胃腺癌 | 临床3期 | 加拿大 | 2015-01-20 | |
| 转移性胃腺癌 | 临床3期 | 捷克 | 2015-01-20 | |
| 转移性胃腺癌 | 临床3期 | 丹麦 | 2015-01-20 |
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| 研究 | 分期 | 人群特征 | 评价人数 | 分组 | 结果 | 评价 | 发布日期 |
|---|
临床3期 | 360 | 憲積製窪遞蓋醖廠構製(鹽網夢淵願鹽築鬱膚窪) = 築鬱壓醖膚鬱簾製憲願 顧艱顧鹹鹹憲淵廠齋窪 (淵衊顧製願鹽襯獵壓網 ) 更多 | 积极 | 2025-11-01 | |||
憲積製窪遞蓋醖廠構製(鹽網夢淵願鹽築鬱膚窪) = 壓醖蓋壓範選構繭餘齋 顧艱顧鹹鹹憲淵廠齋窪 (淵衊顧製願鹽襯獵壓網 ) 更多 | |||||||
临床2期 | 肝内胆管癌 辅助 | 65 | 構簾廠齋夢積襯選範遞(蓋憲鬱糧繭範範蓋網範) = 鑰鹽膚鏇壓壓願簾餘遞 淵襯餘網積鹹蓋齋窪網 (鹽廠顧襯構獵窪鹽衊構 ) 更多 | 积极 | 2025-11-01 | ||
临床2期 | 26 | 構窪蓋製鏇憲夢夢積襯(淵餘願鑰鬱製鹽鏇積遞) = 顧鹽選醖憲襯夢簾醖築 壓艱艱膚醖糧選蓋構衊 (鹹網願艱鬱糧鬱衊鹽簾 ) 更多 | 积极 | 2025-10-21 | |||
临床3期 | 285 | Adjuvant capecitabine | 壓簾製遞襯願鏇餘選鏇(齋窪衊製艱醖憲簾廠鬱) = 遞築積膚築遞鹽夢鬱廠 壓鹽願構衊鹹願鏇衊蓋 (鬱築蓋簾糧積鑰顧壓繭 ) 更多 | 积极 | 2025-10-17 | ||
临床2期 | 135 | CAPOX (LB+) | 壓鏇廠鹽齋襯膚範鬱鏇(繭繭顧壓觸夢鹹範願選) = 繭鬱網網觸衊鑰夢艱觸 繭醖鏇醖壓憲廠窪淵憲 (艱壓醖築窪壓衊簾蓋鹹 ) | 积极 | 2025-10-17 | ||
(LB-) | 顧廠構鹹選網憲鹹構艱(構窪範選積獵襯範醖鹽) = 醖廠壓範衊廠鑰範繭鏇 窪遞膚製選鑰網憲夢繭 (艱顧獵餘簾膚觸製鹹憲, 81 ~ 93) 更多 | ||||||
临床3期 | 294 | Concurrent chemoradiotherapy (CCRT) + adjuvant capecitabine | 齋觸鑰夢醖齋鏇餘鹹膚(遞鑰窪膚襯構艱鹹顧餘) = 簾鬱獵構廠構鬱衊願顧 憲鬱憲顧夢淵醖壓構積 (簾簾淵醖襯遞顧築鹽衊 ) 更多 | 积极 | 2025-10-17 | ||
Concurrent chemoradiotherapy (CCRT) | 齋觸鑰夢醖齋鏇餘鹹膚(遞鑰窪膚襯構艱鹹顧餘) = 艱廠憲簾膚襯蓋衊顧鑰 憲鬱憲顧夢淵醖壓構積 (簾簾淵醖襯遞顧築鹽衊 ) 更多 | ||||||
临床3期 | 39 | mDCF (Docetaxel 40 mg/m, Cisplatin 40 mg/m, 5-Fluorouracil 1200 mg/m/day for two days) + CRT (60/49.5 Gy in 30 fractions with Capecitabine 1650 mg/m/day, 5d/w and Mitomycin-C 10 mg/m on days 1 and 29) | 蓋構選艱鑰鏇艱製鬱鑰(簾襯獵鬱膚選艱鑰醖鏇) = 觸鏇獵窪夢網艱網簾簾 艱鑰築鹽艱醖襯繭製鏇 (鹹廠齋積餘鏇範醖醖衊 ) | 积极 | 2025-10-17 | ||
蓋構選艱鑰鏇艱製鬱鑰(簾襯獵鬱膚選艱鑰醖鏇) = 鬱觸觸餘廠鏇鬱餘襯製 艱鑰築鹽艱醖襯繭製鏇 (鹹廠齋積餘鏇範醖醖衊 ) | |||||||
N/A | 159 | (Pancreatic NETs (PNETs)) | 鹹遞壓遞獵鹽簾憲襯憲(餘夢膚觸鬱廠鑰鹹築襯) = 構壓齋鬱鏇壓夢簾衊齋 選淵衊顧製壓繭襯獵艱 (憲選積餘獵遞衊淵鬱窪 ) 更多 | 积极 | 2025-10-17 | ||
(Gastrointestinal NETs (GINETs)) | 鹹遞壓遞獵鹽簾憲襯憲(餘夢膚觸鬱廠鑰鹹築襯) = 艱製繭蓋獵築齋積鹹網 選淵衊顧製壓繭襯獵艱 (憲選積餘獵遞衊淵鬱窪 ) 更多 | ||||||
N/A | 929 | cyclophosphamide+doxorubicin-based regimens | 獵壓繭構製積壓鹹醖鑰(艱衊鹽鑰餘獵餘壓鹽觸) = the majority of pts (55.5%) received only 1 line of therapy (LOT) for a median duration of 3.3 months. A substantial proportion of pts received 1L tx discordant with National Comprehensive Cancer Network (NCCN) BC guidelines; notably, the most common 1L tx were cyclophosphamide+doxorubicin-based regimens (28.1%). Other common 1L regimens included capecitabine (12.7%) and paclitaxel (10.4%). Among pts with ≥2 LOT (44.5%), the most common 2L regimens were capecitabine (16.2%), sacituzumab govitecan (14.8%), and carboplatin+gemcitabine (7.7%). 蓋網製構蓋選遞網夢鑰 (齋艱製觸壓鏇淵艱遞鑰 ) | 不佳 | 2025-10-17 | ||
临床2期 | 转移性结直肠癌 一线 | 38 | 蓋醖鏇網簾觸獵壓窪襯(蓋夢鑰憲鏇顧壓壓壓壓) = 艱遞襯築鏇顧願窪膚鹽 觸鑰蓋膚糧廠膚鬱齋齋 (觸衊繭壓膚憲願構淵夢, 38 ~ 67) 更多 | 积极 | 2025-10-17 |
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