Open-label, Non-randomized, Single-center Study Investigating the Feasibility, Safety, Tolerability and Efficacy of Suizenji in Unresectable Pancreatic Ductal Adenocarcinoma Patients

This is a feasibility, safety, tolerability, and efficacy research study of an investigational device called "Suizenji", an ultrasound-guided high-intensity focused ultrasound (HIFU) therapy system for the treatment of unresectable pancreatic ductal adenocarcinoma. Focused ultrasound therapy uses a number of small ultrasound generators attached to a bowl-shaped ultrasound generator to emit ultrasound waves from outside to inside the body and focus them on a single point where cancerous cells in the pancreas are located. The targeted area is then heated, which kills the pancreatic cancer cells, and as a result, the patient's life may be prolonged. Experience with Suizenji for pancreatic cancer patients has shown that the "heating" is only a warm feeling in the abdomen during the treatment.

开始日期2025-12-01

申办/合作机构

Sonire Therapeutics Inc

NCT05700448

/ Not yet recruiting临床3期

A Phase III, Randomized, Double-Blind, Multicenter Study of Sugemalimab (CS1001) Plus PGemOx Regimen Versus Placebo Plus PGemOx for Subjects With Relapsed or Refractory Extranodal NK/T-Cell Lymphoma (R/R ENKTL)

The purpose of this study is to evaluate the efficacy and safety of sugemalimab (CS1001) in combination with PGemOx regimen (pegaspargase, gemcitabine, oxaliplatin) in treatment of adult patients with Extranodal NK/T-Cell Lymphoma (ENKTL) who have relapsed or become refractory to asparaginase-based regimens.

开始日期2025-12-01

申办/合作机构

基石药业

NCT07020065

/ Not yet recruiting临床2期IIT

Reduced-dose Carboplatin-doublet-chemotherapy + Cemiplimab vs Cemiplimab Monotherapy in Treatment Naive Older and Frail Patients With Metastatic NSCLC With PD-L1 <50% A Multicentre Randomized Open-label Phase II Trial

Metastatic non-small cell lung cancer is often treated with a combination of chemotherapy and immunotherapy. In patients over the age of 70, some are already in poor health and frail, requiring assistance with daily activities, for example. Older and/or frail individuals often do not tolerate standard-dose chemotherapy well, and their risk of side effects is higher than that of younger patients.
For this reason, the SAKK 18/24 study is investigating how effective and safe chemotherapy is in patients over 70 years of age when the chemotherapy drugs are administered at lower doses than usual. The aim of the study is to find a potentially effective and well-tolerated treatment for older people with metastatic non-small cell lung cancer.

开始日期2025-11-01

申办/合作机构

Swiss Group for Clinical Cancer Research

100 项与吉西他滨相关的临床结果

登录后查看更多信息

100 项与吉西他滨相关的转化医学

登录后查看更多信息

100 项与吉西他滨相关的专利（医药）

登录后查看更多信息

30,067

项与吉西他滨相关的文献（医药）

2025-12-31·Molecular & Cellular Oncology

CHK1 inhibition overcomes gemcitabine resistance in non-small cell lung cancer cell A549

Article

作者: Ma, Xuan ; Liang, Ai-Ling ; Fu, Tian ; Wang, Wen-Xuan ; Ke, Zhi-Yin ; Wang, Xue-Chun ; Liu, Yong-Jun ; Yin, Hai-Han

The purpose of the study is mainly to investigate anti proliferation of non-small cell lung cancer A549 cells and its mechanism by inhibition of CHK1 expression combined with gemcitabine. The mRNA and protein levels of genes were analyzed by RT-qPCR and Western blot, respectively. Cell viability was detected by CCK-8 assay and clone formation assay. The detection of the cell cycle was used by Annexin V/7-amino-actinomycin D apoptosis detection kit. Analysis of DNA damage was done by immunofluorescence and alkaline comet assay. The results showed that inhibition of CHK1 and gemcitabine combination significantly reduced the proliferation ability of the two cell lines. We also revealed the degradation of full-length PARP and reduced Bcl-2/Bax ratio on increased apoptosis. Inhibition of CHK1 expression leads to DNA damage, induces phosphorylation of γ-H2AX, and affects the repair of homologous recombination ability through Rad51. Mechanistically, gemcitabine increased phosphorylation-ATR and phosphorylation-CHK1, indicating activation of the DNA repair system and ATR-CHK1-CDC25A pathway. Inhibition of CHK1 resulted in increased synthesis of CDK2/Cyclin A2 and CDK2/Cyclin E1 complexes, and more cells entered the subsequent cell cycle, leading to S phase arrest and mitotic catastrophe. We identified inhibition of CHK1 as a potential treatment for NSCLC and confirmed that inhibition of this kinase could overcome acquired gemcitabine resistance.

2025-12-31·JOURNAL OF MEDICAL ECONOMICS

Budget impact of introducing glofitamab for treatment of relapsed or refractory diffuse large B-cell lymphoma after two or more lines of systemic therapy in the United States

Article

作者: Li, Jia ; Mahmoudjafari, Zahra ; Masaquel, Anthony ; Parisé, Hélène ; Bercaw, Eric ; Bognar, Katalin ; Wang, Si-Tien

BACKGROUND:

Glofitamab is a T-cell engaging bispecific monoclonal antibody that was granted accelerated approval from the United States Food and Drug Administration for adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified or large B-cell lymphoma arising from follicular lymphoma, after ≥2 lines of systemic therapy (3L+).

METHODS:

A budget impact model was developed for a hypothetical blended commercial/Medicare health plan with 1,000,000 members. Comparators were axicabtagene ciloleucel (Axi-cel), lisocabtagene maraleucel (Liso-cel), tisagenlecleucel (Tisa-cel), loncastuximab tesirine, polatuzumab vedotin + bendamustine + rituximab, rituximab + gemcitabine + oxaliplatin, tafasitamab + lenalidomide, and epcoritamab (Epcor). Total costs included those for drugs, wastage, administration, grade ≥3 adverse reactions, and all-grade cytokine release syndrome) and routine care. Market shares were based on internal projections and expert opinions. Total and per-member per-month (PMPM) net budget impacts over 3 years were calculated.

RESULTS:

Approximately nine patients were projected to be eligible for 3L + DLBCL treatment in a health plan of 1,000,000 members. The introduction of glofitamab as a treatment option resulted in estimated total and PMPM cost savings of $728,697 and -$0.0202, respectively, over 3 years. Costs were reduced across all cost categories but particularly in drug costs. Among the newer therapies, total 3-year cost per treated patient was lowest for glofitamab: $226,658 versus Tisa-cel = $564,113; Axi-cel = $540,002; Liso-cel = $516,272; and Epcor = $335,293. Across all sensitivity analyses, the inclusion of glofitamab had minimal PMPM budget impact, ranging from -$0.0256 to -$0.0108.

CONCLUSIONS:

With the lowest 3-year total cost per treated patient among the newer therapies, glofitamab being an available option in the 3L + DLBCL market is estimated to save a hypothetical 1,000,000-member health plan $728,697 in cumulative total costs and $0.0202 in PMPM costs over 3 years.

2025-12-01·Journal of Gastrointestinal Cancer

Impact of Retroperitoneal Lymphadenopathy (RPLN) on the Outcomes of Locally Advanced Gall Bladder Cancer (GBC) Following Chemotherapy (CT) or Chemotherapy Followed by Consolidation Chemoradiotherapy (CTRT)

Article

作者: Naik, Nagendra ; Priyanka, Parul ; Agrawal, Sushma

INTRODUCTION:

Retroperitoneal lymphadenopathy is considered a metastatic disease in GBC; however, some surgical series of radical surgery with enlarged RPLN who underwent RPLN dissection have shown results marginally inferior to those without enlarged RPLN. Radiological RPLN comprises a major proportion of advanced non-metastatic GBC. There is dilemma in the intent of treatment to be offered in such cases. We are reporting our series of outcome of GBC with RPLN treated with first-line CT followed by consolidation CTRT.

MATERIALS AND METHODS:

Non-metastatic locally advanced GBC with good performance status (KPS ≥ 80) were initiated on first-line CT (cisplatin-gemcitabine), and thereafter, responders were evaluated by CECT-angiography and PET-CT scan for resectability. If found unresectable, they were offered consolidation CTRT to a dose of 45 Gy by conventional fractionation (3D-CRT technique) along with concurrent capecitabine at 1250 mg/m² to GBC and regional lymphatics including RPLN. Thereafter, boost dose of 9 Gy/5# was given to GBC only. Response assessment was done using CECT abdomen by RECIST criteria v 1.1. Outcomes (overall survival) of the two groups (RPLN vs non-RPLN) were computed with Kaplan-Meier survival curves and chi-square tests using SPSS v 20.

RESULTS:

Among 189 patients of advanced non-metastatic GBC recruited from 2011 to 2022, 80 had RPLN. The demographic features of both groups were comparable. Overall, 68% of the patients were women, 30% underwent upfront stenting for obstructive jaundice, and 90% had T3 and T4 disease. Only 10% had undergone upfront laparoscopic staging and had pathologically proven RPLN. Forty percent of the patients received four cycles of CT only and 50% of the patients received six cycles or more and 33% received CTRT. By RECIST criteria, 10% vs 16% achieved complete response (CR), 39% vs 41% achieved partial response (PR), 16% vs 15% achieved stable disease (SD), 2.7% vs 6% had disease progression (PD), and 14.5% vs 3.7% were non-evaluable in non-RPLN group vs RPLN group, respectively. 12% vs 6% could undergo radical surgery in non-RPLN group vs RPLN group (p = 0.03). The median OS was 9 months (95% CI 7.6-10.3 months) vs 10 months (95% CI 8-9.8 months) (p = NS) in non-RPLN group vs RPLN group, respectively. In those who received CT only, the median OS was 7 months vs 8 months, while in those who received CT followed by CTRT, the median OS was 14 months vs 13 months (p = 0.65) in non-RPLN group vs RPLN group, respectively.

CONCLUSIONS:

Based on this analysis, we conclude that RPLN constitutes a major proportion of advanced non-metastatic GBC and has outcomes similar to those without RPLN if treated with radical intent. RPLN should not be considered a metastatic disease and should be treated with radical intent.

2,080

项与吉西他滨相关的新闻（医药）

2025-07-15

·今日头条

WT1-DC疫苗联合化疗逆转癌王耐药困局，胰腺癌中位总生存超3年

胰腺导管腺癌（PDAC）是一种死亡率极高的恶性肿瘤，其显著特征是对细胞毒性化疗和放射疗法存在固有耐药性。这一特性导致无法切除的胰腺导管腺癌（UR-PDAC）患者临床治疗效果不佳，因此，研发既针对肿瘤细胞、又能靶向肿瘤微环境（TME）的新型疗法，成为改善患者预后的迫切需求。近日，《免疫肿瘤学杂志》报道了一项突破性研究：应用多功能 WT1-DC 疫苗治疗不可切除晚期胰腺导管腺癌（UR-PDAC）的 Ⅰ 期临床试验，公布了令人振奋的初步数据 —— 所有入组患者中位OS超3年、PFS超2年！WT1-DTH 长期阳性患者生存期更是达4.5 年！这一突破为长期困于治疗绝境的晚期胰腺癌患者点亮了跨越数年的生存希望，让难治性胰腺癌的治疗迎来了值得期待的新曙光！ ▲截图源自“PMC” WT1-DC疫苗联合化疗让晚期患者肿瘤负荷大降，生存期达3.52年，中位无进展生存期达2.23年 WT1是一种与血管生成、肿瘤进展、侵袭及转移密切相关的转录因子，在肿瘤发生中发挥致癌作用。它不仅表达于胰腺导管腺癌（PDAC）细胞，还存在于肿瘤微环境（TME）的癌症干细胞、髓系抑制细胞（MDSC）及肿瘤血管中，这使其成为极具潜力的癌症治疗靶点。而树突状细胞（DC）作为专业抗原呈递细胞，在启动和调节肿瘤相关抗原特异性免疫反应中起着关键作用。基于此，研究团队开发出一种新型WT1肽脉冲树突状细胞（WT1-DC）疫苗，Ⅰ期临床研究数据同步发表于《免疫肿瘤学杂志》中。该研究共纳入10例不可切除晚期胰腺导管腺癌（UR-PDAC）患者，包括6例局部晚期胰腺导管腺癌（LA-PDAC）、3例转移性胰腺导管腺癌（M-PDAC）、1例术后复发患者，均经病理确诊为腺癌，且表达WT1和MHCⅠ类分子。入组后，先接受白蛋白结合型紫杉醇+吉西他滨联合化疗，再接受WT1-DC疫苗治疗。结果显示：在9例可评估预后的患者中，WT1肽特异性迟发型超敏反应（WT1-DTH）长期阳性患者（n=4）的临床疗效显著优于短期阳性患者（n=5），且所有WT1-DTH长期阳性患者的生存期均达到至少4.5年。此外，所有患者的肿瘤负荷均有下降（降幅0.0%-57.4%）（详见下图）。 ▲图源“J Immunother Cancer”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除其中 7例患者（6例局部晚期胰腺导管腺癌、1例转移性胰腺导管腺癌）实现部分缓解（PR），其余 3例维持长期疾病稳定（SD）。治疗约6个月后，患者肿瘤最大标准摄取值（SUVmax）显著下降（p=0.006）。下图展示了4例不可切除晚期胰腺导管腺癌（UR-PDAC）患者（编号WT1-DC-01、WT1-DC-03、WT1-DC-05、WT1-DC-09），在接受治疗前后的CE-CT与¹⁸F-FDGPET/CT影像对比，清晰展示了治疗带来的变化。 ▲图源“J Immunother Cancer”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除此外，生存数据更为亮眼： 9例患者的中位无进展生存期（PFS）达2.23年，中位总生存期（OS）达3.52年（详见下图A）。其中， 5例局部晚期胰腺导管腺癌（LA-PDAC）患者的中位PFS为2.48年，总生存期尚未达到；而 3例转移性胰腺导管腺癌（M-PDAC）患者的中位PFS达1.37年、中位OS达2.41年（详见下图B）。 ▲图源“J Immunother Cancer”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除综上，通过WT1-DC疫苗联合化疗的免疫治疗方案，可强效激活UR-PDAC患者的WT1特异性免疫反应，有望调节肿瘤微环境并为部分患者争取转化手术机会，最终带来显著的临床获益。小编寄语树突状细胞（DC）作为体内唯一能激活初始T细胞的抗原提呈细胞，在免疫反应中占据核心地位。目前，DC疫苗虽多数仍处于早期临床试验阶段，但已在部分国家正式应用于临床。对于早期肿瘤患者，术后采用DC疫苗联合放化疗的辅助治疗方案，可通过清除残留癌细胞、形成免疫记忆，降低复发转移风险。目前，树突状疫苗在日本、德国等，用于临床辅助治疗多种癌症，包括皮肤癌、肝癌、肺癌、肾癌、乳腺癌等。想了解树突状细胞疫苗等抗癌新技术更多讯息的患者，可将近期病理报告、影像学检查资料、治疗经历等，提交至全球肿瘤医生网医学部，进行初步评估或了解详细的入排标准。参考资料 [1]Koido S,et al.Dendritic cells pulsed with multifunctional Wilms' tumor 1 (WT1) peptides combined with multiagent chemotherapy modulate the tumor microenvironment and enable conversion surgery in pancreatic cancer. J Immunother Cancer. 2024 Oct 8;12(10):e009765. https://pmc.ncbi.nlm.nih.gov/articles/PMC11474828/ 本文为全球肿瘤医生网原创，未经授权严禁转载

临床结果疫苗放射疗法临床2期临床3期

2025-07-14

·ioncology

APPLE 2025丨曾昭冲教授：免疫治疗时代下的肝内胆管癌放射治疗

编者按：在免疫治疗时代，放射治疗正从传统的局部肿瘤控制手段转变为激活全身性抗肿瘤免疫的关键"催化剂"。第15届亚太原发性肝癌专家联盟会议（APPLE 2025）上，复旦大学附属中山医院曾昭冲教授分享了免疫治疗时代下肝内胆管癌（iCCA）放射治疗的最新进展。本刊特邀请曾教授进行了深度访谈。针对iCCA这一免疫抑制性强的难治性肿瘤，曾教授系统阐释了放疗通过重塑肿瘤免疫微环境、增强抗原释放与递呈、促进T细胞浸润等机制，与免疫治疗产生协同效应的科学基础。同时，他详细解析了联合方案在临床实践中的应用策略。面对疗效预测标志物缺乏、肿瘤微环境免疫抑制等挑战，曾教授提出开发新型生物标志物、优化联合方案、调控肿瘤微环境等未来研究方向，为突破iCCA治疗瓶颈提供了重要思路。图1. 曾教授和与会专家进行现场交流图2. 曾教授及团队成员在APPLE 2025现场图3. 曾教授在会上作专题报告01《国际肝病》：曾教授，在免疫治疗时代，放疗作用于iCCA时，是怎样与免疫系统产生协同作用，进而激发机体抗肿瘤免疫反应的？能否详细阐述一下其中的细胞和分子层面的机制？曾昭冲教授复旦大学附属中山医院感谢您的提问。在免疫治疗时代，放疗已不仅是局部治疗手段，更成为激活全身性抗肿瘤免疫的重要“催化剂”。尤其在iCCA这类免疫抑制性强、传统治疗响应有限的肿瘤中，放疗与免疫治疗的协同具有独特价值。其协同机制主要涉及以下几个关键层面：1、放疗重塑肿瘤免疫微环境（TIME）肝内胆管癌的肿瘤免疫微环境通常表现为“冷肿瘤”特征：T细胞浸润少、免疫抑制细胞（如Tregs等）富集、免疫检查点分子高表达。放疗通过物理能量直接杀伤肿瘤细胞的同时，深度重塑这一微环境。2、放疗增强肿瘤抗原释放与递呈一方面，放疗导致DNA双链断裂，增加肿瘤细胞突变负荷，产生新抗原；同时释放大量肿瘤相关抗原；另一方面，放疗促进树突状细胞成熟与交叉递呈，树突状细胞将吞噬的肿瘤抗原交叉递呈给CD8⁺ T细胞，启动特异性T细胞应答。3、放疗促进T细胞应答的激活与浸润放疗上调肿瘤细胞趋化因子9/10/11表达，通过结合效应T细胞表面CXCR3受体，驱动CD8+T细胞向肿瘤灶浸润。放疗后全身性抗肿瘤反应的产生依赖于：抗原扩散：放疗灶释放的抗原被树突状细胞捕获，激活全身性T细胞反应；循环T细胞扩增：放疗后外周血中肿瘤特异性T细胞克隆扩增，迁移至未照射的转移灶；系统免疫记忆形成：放疗联合ICI可诱导长效记忆T细胞，降低复发风险。综上所述，放疗在iCCA治疗中正从“局部武器”转变为“免疫系统启动器”。通过诱导免疫原性细胞死亡、重塑免疫微环境、增强抗原递呈与T细胞应答，放疗为免疫治疗创造了有利条件。未来需进一步探索iCCA特异性抗原库、肝微环境调控及个体化联合策略，以突破这一难治性肿瘤的治疗瓶颈。02《国际肝病》：目前在 iCCA 的临床治疗中，放疗联合免疫治疗有哪些常见的联合方案？不同方案在疗效和安全性上是否存在差异，如何根据患者的具体情况选择最合适的联合方案？曾昭冲教授复旦大学附属中山医院免疫检查点抑制剂（ICIs）联合放疗的创新治疗模式，为晚期iCCA患者提供了新的希望。这种联合策略的基础在于放疗的免疫调节效应-它不仅能直接杀伤肿瘤细胞，还能重塑肿瘤微环境，将“冷肿瘤”转化为“热肿瘤”。根据免疫治疗药物的组合方式及放疗时序安排，目前临床实践中的联合方案主要分为四类，各有其特定的适应人群和疗效特征。1. 双联方案：放疗联合PD-1/PD-L1抑制剂这是目前研究较多的一种组合方式，主要适用于体能状态较好（ECOG 0-1）、无严重肝功能障碍的晚期患者，尤其对传统免疫治疗标志物（PD-L1、TMB）表达低的患者具有突破性价值。放疗可通过诱导肿瘤细胞释放抗原、增强肿瘤微环境的免疫原性，从而提高免疫检查点抑制剂的疗效。2022年放疗顶刊红皮杂志报道了放疗联合抗PD-1对比化疗在胆管癌中的疗效，接受放疗联合抗PD-1抑制剂患者的OS和DFS显著优于接受化疗组（中位 OS：17.0 vs 11.5 个月，P = 0.01；中位 DFS：12.5 vs 7.9 个月，P = 0.008）。放疗联合免疫治疗组中严重不良事件的发生率较化疗组显著降低（7.7%对79.4%，P<0.001）。2. 三联方案：放疗联合双免疫检查点抑制剂（如PD-1联合CTLA-4抑制剂）或及靶向治疗（三联方案）这一强化方案适用于肿瘤负荷较高、伴微血管侵犯的患者，通过双重免疫阻断或多通路协同增强抗肿瘤效应。3. 四联方案：放疗+免疫+靶向+化疗（GEMOX）这一高强度方案适用于高肿瘤负荷、快速进展或伴主要血管侵犯的晚期患者，我们团队2023年已经报道在四药三联的基础上加入放疗的临床疗效和安全，我们分析了41例不可切除iCCA患者接受放疗联合仑伐替尼、PD-1抑制剂及GEMOX化疗（吉西他滨+奥沙利铂）后，患者中位无进展生存期（PFS）为11个月，ORR达49.1%，显著优于传统化疗。安全性方面，四联方案≥3级不良事件发生率为31.7%（13/41例），包括骨髓抑制、高血压及肝功能障碍，但经剂量调整后均可控，无治疗相关死亡。不同联合方案的疗效差异主要源于以下几个方面：肿瘤分子分型特征、肿瘤负荷与分期、患者肝功能储备状态与全身状况和患者既往治疗史。如果患者有突变靶点，首选分子靶向治疗，在靶向药物控制的基础上联合局部治疗。局部晚期可选择新辅助放疗+GEMOX+PD-1抑制剂，争取降期手术。IV期寡转移疾病采用SBRT（所有病灶）联合系统性治疗，若弥漫转移，优选系统治疗+原发灶姑息放疗。此外，如果Child-Pugh A级且ECOG≤1：耐受性强，推荐四联方案或强化三联方案。若Child-Pugh B级或ECOG≥2：选择低毒双联方案（如SBRT+PD-1），避免联合化疗。而对于既往接受多线治疗失败的患者，三联方案或双免疫治疗可能提供新的治疗机会。03《国际肝病》：对于接受放疗联合免疫治疗的 iCCA 患者，如何准确地评估其治疗效果？除了传统的影像学和肿瘤标志物检测方法外，有没有一些新的评估指标或技术正在研究或应用中？曾昭冲教授复旦大学附属中山医院传统的评估方法主要包括影像学检查（如CT、MRI）和血清肿瘤标志物（如CA19-9）检测。影像学检查通过观察肿瘤的大小变化来评估疗效，但存在一定的滞后性，且无法准确区分肿瘤坏死与存活组织。血清CA19-9水平的变化虽然可以辅助评估疗效，但其特异性和敏感性均有限，且易受其他因素干扰。近几年一些新兴的评估指标和技术越来越多的尝试应用于临床：1. 免疫检查点抑制剂（ICIs）的疗效与多种生物标志物相关，包括PD-L1表达、微卫星不稳定性（MSI）、DNA错配修复（MMR）缺陷和肿瘤突变负荷（TMB）等。2. 有研究发现，接受免疫治疗的胆管癌患者，出现irAEs与更好的疾病控制、更长的总生存期（OS）和无进展生存期（PFS）相关。因此，irAEs可能作为免疫治疗疗效的预测指标。3. 循环肿瘤DNA是一种新兴的生物标志物，可通过血液检测肿瘤特异性突变，实时监测肿瘤负荷变化，评估治疗反应和早期发现肿瘤进展。虽然目前ctDNA在iCCA中的应用仍处于研究阶段，但其潜力巨大。4. 功能影像学技术如动态增强MRI（DCE-MRI）、扩散加权成像（DWI）和正电子发射断层扫描（PET）等，可提供肿瘤血流、代谢等信息，更早期、更准确地评估治疗反应。这些技术已在其他肿瘤类型中显示出优势，正在逐步引入iCCA的疗效评估中。5. 人工智能（AI）和影像组学技术通过高通量提取影像学特征，建立预测模型，有望提高疗效评估的准确性。这些技术可以挖掘影像中肉眼无法识别的信息，为个体化治疗提供依据。鉴于单一评估方法的局限性，临床上推荐采用多种方法综合评估。随着研究的深入，更多生物标志物和先进技术将被应用于临床，进一步提高疗效评估的准确性和及时性。04《国际肝病》：在 iCCA 的放疗联合免疫治疗过程中，目前面临的主要挑战有哪些？未来有哪些研究方向和策略可以探索，以进一步提高患者的生存获益？曾昭冲教授复旦大学附属中山医院当前面临的主要挑战主要包括以下几个方面：1. 缺乏有效的疗效预测生物标志物目前，我们缺乏能够准确预测放疗联合免疫治疗疗效的生物标志物。虽然PD-L1表达、微卫星不稳定性（MSI）和肿瘤突变负荷（TMB）等被尝试用于预测免疫治疗的效果，但在iCCA中，这些标志物的预测价值有限。2. 肿瘤微环境（TME）的免疫抑制特性iCCA的肿瘤微环境具有高度的免疫抑制性，包括丰富的肿瘤相关巨噬细胞（TAMs）、髓源性抑制细胞（MDSCs）和调节性T细胞（Tregs），这些细胞会削弱免疫治疗的效果。3. 治疗相关不良反应的管理放疗联合免疫治疗可能带来叠加或协同的不良反应，如放射性肝炎、免疫相关性肺炎、结肠炎等。如何平衡疗效与安全性，优化治疗方案，降低不良反应发生率，是临床实践中亟需解决的问题。4. 治疗抵抗机制尚未完全阐明部分患者对放疗联合免疫治疗存在原发性或获得性抵抗，其机制尚未完全明确。深入了解抵抗机制，对于制定克服策略至关重要。那么，针对以上可能面临的挑战，未来的研究方向和策略主要有以下方面：1. 开发新型生物标志物未来研究应致力于发现新的、更可靠的生物标志物，以精准筛选可能从放疗联合免疫治疗中获益的患者。整合AI预测模型、空间多组学和液体活检，构建动态疗效评估体系是未来发展方向。2. 优化联合治疗方案探索放疗与免疫治疗的最佳联合模式，包括放疗剂量、分割方式、照射靶区与免疫治疗的时序安排等。同时，研究放疗联合双免疫检查点抑制剂（如PD-1联合CTLA-4抑制剂）或联合靶向治疗的疗效和安全性。3. 调控肿瘤微环境通过靶向TME中的免疫抑制细胞或分子，如TAMs、MDSCs、Tregs，或利用溶瘤病毒、细胞因子等手段，改善TME的免疫状态，提高免疫治疗的疗效。4. 开展多中心、随机对照临床试验目前，放疗联合免疫治疗在iCCA中的临床证据多为小样本、单臂研究。未来需要开展大规模、多中心的随机对照临床试验，以明确其疗效和安全性，为临床实践提供高级别证据。5. 探索新型免疫治疗策略包括肿瘤疫苗、过继性细胞治疗（如CAR-T细胞）、双特异性抗体等新兴免疫治疗手段，与放疗的联合应用也值得深入研究。综上所述，在系统治疗与局部治疗的协同实体瘤治疗的新范式下，放疗联合免疫治疗在iCCA中展现出良好的前景，但仍面临诸多挑战。通过深入研究生物标志物、优化治疗方案、调控肿瘤微环境以及开展高质量临床试验，我们有望进一步提高患者的生存获益。APPLE 2025曾昭冲教授二级教授/主任医生/博士生导师复旦大学附属中山医院中国研究型医院学会放射肿瘤学分会副主委中国抗癌协会诊疗一体化专委会副主委肿瘤放射生物与多模态诊疗专业委员会副主委 CSCO肝癌专业委员会常委中国医师协会肝癌专业委员会常委杂志发表文章：以第一或通讯作者身份发表SCI论文130篇，中文70篇。主编《原发性肝癌放射治疗临床实践》第1和第2版、《原发性肝癌精准放疗靶区勾画图谱》，执笔《Consensus for SBRT for HCC from the 7th APPLE》、2016年和2020年《原发性肝癌放疗共识》。获国家科技二等奖1项和省部级科技奖4项。主持国家级课题9项。评选为上海市优秀学术带头人、上海市领军人才。2023年上海好医生。（来源：《国际肝病》编辑部）声明凡署名原创的文章版权属《肿瘤瞭望》所有，欢迎分享、转载。本文仅供医疗卫生专业人士了解最新医药资讯参考使用，不代表本平台观点。该等信息不能以任何方式取代专业的医疗指导，也不应被视为诊疗建议，如果该信息被用于资讯以外的目的，本站及作者不承担相关责任。

免疫疗法放射疗法细胞疗法

2025-07-14

·BioSpace

After Three Strikes, Relmada Abandons Depression Drug Esmethadone

iStock, Wel_nofri The development saga for the depression molecule has been rocky for years, unable to ease symptoms in multiple late-stage trials. Relmada Therapeutics has halted development of its investigational NMDA receptor blocker esmethadone, ending what has been a rough journey for the asset. The company made the announcement in an SEC filing on Friday. The company said that it will terminate a January 2018 licensing agreement , under which it obtained global rights to esmethadone. The molecule was originally deveoped by Charles Inturrisi, a professor at Weill Cornell Medical. Inturrisi then himself licensed it to Medeor, co-founded Paolo Manfredi. Medeor merged with Relmada in 2013. As per the terms of the original contract, Relmada paid a nonrefundable sum of $180,000 upfront to Inturrisi and Manfredi, plus $45,000 every three months ever since. Those quarterly payments were intended to continue until certain conditions were met, including the first market sale of esmethadone or the expiration of its patent. None of such events occurred over the course of the partnership. Esmethadone’s development history has been fraught for some time now. In October 2022, the drug asset failed the Phase III RELIANCE III trial in major depressive disorder (MDD), unable to significantly ease the severity of depressive symptoms as a monotherapy versus placebo. Esmethadone delivered another late-stage disappointment in December of the same year, when the drug again showed no significant benefit in the RELIANCE I study, this time as an adjunctive MDD treatment. For both RELIANCE I and RELIANCE III trials, Relmada blamed an “unplausible placebo response” for the lack of significant efficacy signals for esmethadone. Then, in December 2024, the Phase III RELIANCE II also ended in failure , with an interim analysis finding a high likelihood of futility. A couple of weeks later, Relmada discontinued RELIANCE II and the Phase III RELIGHT study, also in MDD. With esmethadone now gone from its pipeline, Relmada has “made the exploration of strategic product acquisitions our primary focus,” according to a note to investors on its website . The company is focusing its efforts on NDV-01, a Phase II proprietary sustained-release formulation of gemcitabine and docetaxel being trialed for non-muscle invasive bladder cancer. Relmada licensed NDV-01 from Trigone Pharma in March. Phase II data presented in April showed an 85% three-month overall response rate . Relmada is the latest biotech to stumble in the difficult depression space. Last month, for example, Alto Neuroscience’s ALTO-203 was unable to significantly boost mood in patients with MDD in a Phase II study, forcing the California company to dig into exploratory endpoints and look at EEG biomarkers for signals of efficacy. In February, Supernus Pharmaceuticals likewise had a mid-stage stumble when its asset SPN-820 failed to improve symptom burden in patients with treatment-resistant depression. Even Big Pharma seems to have been having trouble making headway into depression, with Johnson & Johnson in March discontinuing the late-stage VENTURA program after its kappa opioid receptor blocker aticaprant failed to demonstrate sufficient efficacy signals to support continued development.

临床2期临床3期引进/卖出临床结果临床失败

100 项与吉西他滨相关的药物交易

登录后查看更多信息

外链

KEGG	Wiki	ATC	Drug Bank
D02368	吉西他滨	L01BC05	DB00441

研发状态

批准上市

10 条最早获批的记录,

后查看更多信息

适应症	国家/地区	公司	日期
转移性乳腺癌	美国	Avyxa Pharma	2025-06-27
非小细胞肺癌	美国	Avyxa Pharma	2025-06-27
卵巢癌	美国	Avyxa Pharma	2025-06-27
胰腺腺癌	美国	Avyxa Pharma	2025-06-27

未上市

10 条进展最快的记录,

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
胰腺癌	临床3期	-	RenovoRx, Inc.	2023-06-01
转移性胰腺导管腺癌	临床3期	澳大利亚	Panbela Therapeutics, Inc.	2022-08-04
局部晚期胰腺腺癌	临床3期	美国	RenovoRx, Inc.	2018-03-12
局部晚期胰腺腺癌	临床3期	比利时	RenovoRx, Inc.	2018-03-12
晚期鳞状细胞肺癌	临床3期	美国	Sanofi	2010-03-01
晚期鳞状细胞肺癌	临床3期	比利时	Sanofi	2010-03-01
晚期鳞状细胞肺癌	临床3期	加拿大	Sanofi	2010-03-01
晚期鳞状细胞肺癌	临床3期	法国	Sanofi	2010-03-01
晚期鳞状细胞肺癌	临床3期	德国	Sanofi	2010-03-01
晚期鳞状细胞肺癌	临床3期	匈牙利	Sanofi	2010-03-01

登录后查看更多信息

临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT02807181 (SIRCCA, CTgov)	临床2/3期	不可切除的肝内胆管癌	89	gemcitabine+Cisplatin (Chemotherapy (Cisplatin-Gemcitabine))	壓顧夢糧鏇鬱廠範鏇構(繭齋糧壓選衊觸構構範) = 繭築廠夢積淵膚鬱壓淵鏇醖網觸廠衊鬱憲艱繭 (壓夢選鏇獵製醖積繭網, 憲願繭醖襯廠簾範鬱憲 ~ 鹽選鏇鹹觸製壓顧選蓋) 更多	-	2025-05-09
				Radiation: SIRT + chemotherapy (cisplatin-gemcitabine)+gemcitabine+Cisplatin (Radiation: SIRT + Chemotherapy (Cisplatin-Gemcitabine))	壓顧夢糧鏇鬱廠範鏇構(繭齋糧壓選衊觸構構範) = 鑰鬱鑰衊選鑰簾醖鹽範鏇醖網觸廠衊鬱憲艱繭 (壓夢選鏇獵製醖積繭網, 鹽糧醖遞鑰艱築艱構壓 ~ 憲鏇夢糧憲夢願構製鏇) 更多
NCT04602078 (AUREA \| SOGUG-AUREA, CTgov)	临床2期	膀胱尿路上皮癌 \| 局部晚期尿路上皮癌 \| 转移性尿路上皮癌	82	Cisplatin 70 mg/m2+Gemcitabine 1000 mg/m2+Atezolizumab 1200 mg/m2	選淵選鏇範廠鑰顧鏇餘 = 壓壓夢簾糧願築積齋遞簾繭廠顧繭獵網構膚築 (夢夢鬱製艱範淵膚窪壓, 糧憲製製蓋鑰夢願範願 ~ 遞選襯艱網構餘憲觸繭) 更多	-	2025-04-24
ASCO_GU2025	N/A	非肌层浸润性膀胱肿瘤	30	Intravesical Gemcitabine and Docetaxel	觸夢鑰衊願鏇範餘醖鹹(鑰艱襯積糧簾繭醖願築) = 壓製顧遞範淵顧鏇憲襯鏇衊構襯襯鹽襯餘遞憲 (網鑰遞觸積襯簾餘積糧 ) 更多	积极	2025-02-13
ASCO_GU2025	N/A	非肌层浸润性膀胱肿瘤 Consensus subtyping models	143	Intravesical Bacillus Calmette-Guerin (BCG)	構醖衊繭窪網襯網餘選(範襯餘鬱構網鑰襯憲鏇) = 願鹹簾觸繭鹽觸鹽鑰獵範憲網憲鹹艱鹽醖願醖 (繭範襯淵餘壓觸艱窪繭 )	积极	2025-02-13
				Sequential intravesical gemcitabine and docetaxel (Gem/Doce)	構醖衊繭窪網襯網餘選(範襯餘鬱構網鑰襯憲鏇) = 鑰鬱艱襯簾遞壓齋鏇簾範憲網憲鹹艱鹽醖願醖 (繭範襯淵餘壓觸艱窪繭 )
NCT01972919 (CTgov)	临床2期	不能切除性胰腺癌	23	Radiation Therapy+Gemcitabine+Capecitabine	構鏇簾餘艱糧餘糧簾淵 = 鹽繭襯築顧夢築廠遞窪夢構窪襯簾襯醖餘積廠 (夢糧鑰淵遞築夢鹽襯繭, 夢願齋襯鏇壓餘積鹽鑰 ~ 鏇築醖蓋窪壓鹽製壓簾) 更多	-	2025-02-10
NCT04229004 (Precision Promise (PrP), ASCO_GI2025)	临床2/3期	转移性胰腺癌二线	317	Pamrevlumab plus nab-paclitaxel/gemcitabine (Pam + GA)	窪鏇積廠願憲觸鹹積鑰(繭鹽餘繭鏇範壓膚糧蓋): HR = 1.18 (95% CI, 0.88 ~ 1.56), P-Value = 0.14 更多	不佳	2025-01-23
				Gemcitabine/Abraxane (GA)
ASCO_GI2025	N/A	胰腺导管腺癌 DNA methylation changes	184	Gemcitabine	襯齋構餘淵膚鏇範淵觸(鹹鹹觸憲選範壓壓鬱簾) = 簾鹽廠積鹹糧醖選窪憲獵淵積餘醖壓鏇齋膚範 (鹽廠網遞選餘夢範鏇糧 ) 更多	-	2025-01-23
				Fluorouracil (5-FU)	襯齋構餘淵膚鏇範淵觸(鹹鹹觸憲選範壓壓鬱簾) = 醖觸衊範願艱選遞構壓獵淵積餘醖壓鏇齋膚範 (鹽廠網遞選餘夢範鏇糧 )
NCT03257033 (TIGeR-PaC, ASCO_GI2025)	临床3期	局部晚期胰腺腺癌	19	Intra-arterial gemcitabine	顧糧蓋鹹構構鏇簾製顧(鬱網醖壓艱艱齋鹹鬱淵) = 夢廠獵觸餘觸衊選膚構繭淵簾夢觸積窪齋鹽醖 (網顧襯鹹製獵網廠醖鹽 )	积极	2025-01-23
				Intravenous gemcitabine	顧糧蓋鹹構構鏇簾製顧(鬱網醖壓艱艱齋鹹鬱淵) = 廠遞願壓糧構選製蓋繭繭淵簾夢觸積窪齋鹽醖 (網顧襯鹹製獵網廠醖鹽 )
ACTRN12623000223639 (ASCO_GI2025)	N/A	晚期胰腺导管腺癌	30	Gemcitabine + Nab-paclitaxel + LSTA-1 + Durvalumab	繭範憲襯獵夢鹽憲構廠(網壓衊願積構繭淵願糧) = 壓襯願遞淵製餘艱簾鑰憲淵範糧廠鏇範鹹醖鏇 (窪壓膚獵夢選夢蓋繭襯 )	积极	2025-01-23
ASH2024	N/A	弥漫性大B细胞淋巴瘤	-	Glofitamab with Gemcitabine and Oxaliplatin	窪積夢簾窪糧鑰憲顧願(鬱觸鹽餘築遞夢醖築鏇) = 顧艱簾顧窪衊醖製餘夢遞構齋築膚淵觸製廠鹽 (蓋齋鑰製鏇鏇鹹窪鏇繭, NA) 更多	-	2024-12-09
				Rituximab with Gemcitabine and Oxaliplatin	窪積夢簾窪糧鑰憲顧願(鬱觸鹽餘築遞夢醖築鏇) = 夢憲製憲遞遞壓遞膚顧遞構齋築膚淵觸製廠鹽 (蓋齋鑰製鏇鏇鹹窪鏇繭, NA) 更多