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胃癌腹膜转移（GCPM）是晚期胃癌治疗中最棘手的难题之一，其预后差、治疗选择有限。在2025年国际胃癌大会（IGCC）上，包括DRAGON-01研究在内的三项入选口头报告的研究聚焦于多学科联合治疗方案的创新探索，涵盖常温腹腔化疗、腹腔-静脉联合化疗及加压雾化化疗等策略，为改善患者生存提供了重要循证依据。这些研究不仅验证了局部强化治疗与全身系统治疗的协同价值，更揭示了精准筛选患者、动态调整方案的重要性。本文整合三项研究核心数据，结合临床转化现状，为胃癌腹膜转移的个体化治疗提供新思路。

DRAGON-01研究结果：腹腔内+静脉紫杉醇联合S-1显著改善胃癌腹膜转移患者的总生存期

上海交通大学医学院附属瑞金医院严超教授领衔的DRAGON-01研究入选本次大会口头摘要环节，摘要号为02.2.22。

DRAGON-01研究是一项Ⅲ期、多中心、随机试验，纳入中国9家癌症中心的患者。入组条件为18~75岁、确诊胃腺癌伴腹膜转移、体能状态良好且未接受过化疗或放疗。

患者按2：1随机分配至NIPS组（第1、8天静脉紫杉醇50 mg/m2+腹腔紫杉醇20 mg/m2，第1~14天口服S-1 80 mg/m2）或PS组（第1、8天静脉紫杉醇70 mg/m2，第1~14天口服S-1 80 mg/m2）。主要终点为总生存期（OS），采用Kaplan-Meier曲线和log-rank检验分析，并进行Cox回归多变量分析。

2017年5月~2022年3月，共246例患者接受筛查，222例纳入分析：NIPS组148例，PS组74例。

研究结果显示，截至2024年3月，NIPS组和PS组的中位OS分别为19.4个月和13.9个月（HR=0.66；P=0.005）。NIPS组的1年和2年生存率更高（69.6% vs. 54.1%，37.2% vs. 20.3%）。常见的3~4级不良事件包括白细胞减少和中性粒细胞减少，无治疗相关死亡。

总之，该研究证实腹腔内+静脉紫杉醇联合S-1可显著改善胃癌腹膜转移患者的总生存期，并且毒性可控。

日本20年经验：常温腹腔内及全身化疗治疗胃癌腹膜转移安全有效

第二项研究是由日本东京大学Hironori Ishigami教授领衔的研究，摘要号为02.2.21。

在20年临床实践基础上，Hironori Ishigami教授开发了一种多学科治疗方案，包括全身化疗、腹腔内（IP）紫杉醇（PTX）或多西他赛（DOC），以及化疗有效后的胃切除术。

在本项研究中，研究者进行了五项方案的Ⅰ期和Ⅱ期试验：S-1/PTX联合IP PTX、S-1/奥沙利铂联合IP PTX、S-1/顺铂联合IP PTX、卡培他滨/顺铂联合IP DOC，以及FOLFOX联合IP PTX。研究者还开展了Ⅱ期PHOENIX-GC研究，旨在比较S-1/PTX联合IP PTX与S-1/顺铂的疗效。此外，研究者回顾性评估了胃切除术的安全性和有效性。

结果显示，在Ⅰ期试验中，IP PTX和IP DOC的推荐剂量分别为20~40 mg/m2和10 mg/m2，全身性不良事件常见。在Ⅱ期试验中，FOLFOX联合IP PTX方案对口服摄入不足患者的1年OS率为56%，其他四项试验的1年OS率为72%~78%。

PHOENIX-GC试验未能证明S-1/PTX联合IP PTX优于S-1/顺铂，但调整腹水量的探索性分析提示IP PTX具有临床获益。

在三项多中心试验的222例患者中，93例在腹膜转移显著缩小后接受了胃切除术，手术组与非手术组的中位OS分别为26.3个月和12.3个月。

总之，本研究证明长期常温腹腔内联合全身化疗的多学科治疗对胃癌腹膜转移安全有效。

PlPAC联合FOLFOX治疗胃癌腹膜转移显示出有前景的疗效

第三项研究来自立陶宛维尔纽斯医学院Martynas Luk?ta教授，摘要号为02.2.23，研究报告了PlPAC联合FOLFOX化疗治疗胃癌腹膜转移的阶段性结果。

该研究是研究者发起的单臂Ⅱ期试验纳入经组织学确诊的胃癌腹膜转移且未接受过治疗的患者。患者接受3个周期的PlPAC（顺铂+阿霉素）和6个周期的全身FOLFOX化疗。主要终点为根据RECIST v1.1标准评估的客观缓解率（ORR），次要终点包括发病率、生存期和生活质量。采用Simon两阶段极小化设计，计划入组37例患者。

结果显示，2022年11月至2023年12月，20例患者入组，17例完成治疗，1例（5%）因毒性终止。第4个FOLFOX周期后，5例（29.4%）患者达到ORR。至第三次PlPAC时，腹膜癌指数（PCI）中位数从14降至8（差异无统计学意义）。完全病理缓解率（PRGS评分1）在第三次PlPAC后升至29.4%，阴性细胞学率升至47.1%，无腹水患者比例升至70.6%。2例患者接受R0减瘤手术。随访7个月后，8例患者存活，4例无进展。

总之，阶段性结果表明，PlPAC联合FOLFOX治疗胃癌腹膜可行、耐受性良好，且在影像学和病理学上显示出有前景的疗效。

未来展望：精准化与个体化治疗是胃癌腹膜转移的大趋势

三项研究从不同维度推进了胃癌腹膜转移的治疗边界：①多学科整合：日本经验表明，化疗降期后手术可显著延长生存，需进一步优化患者筛选标准；②给药方式革新：DRAGON-01试验证实腹腔给药的临床价值，未来可探索生物标志物指导的精准用药；③新技术应用：PlPAC联合FOLFOX的早期疗效令人鼓舞，需扩大样本量验证长期生存获益。相信未来随着转化医学研究的深入，胃癌腹膜转移或将从“终末期”定义转变为“可治愈性疾病”，为患者带来更多生机。

摘要原文：

02.2.21-Normothermicintraperitoneal andsystemic chemotherapy for gastric cancerwith peritoneal metastases: 20-yearexperience in Japan

Background:

The prognosis of gastric cancer withperitoneal metastasis remains poor despite recent advances in systemic chemotherapy. We have developeda multidisciplinary treatment with systemicchemotherapy and intraperitoneal (lP) paclitaxel (PTX) ordocetaxel(DOC) combined with gastrectomy after response to chemotherapy.

Methods:

We performed phase l and ll trials of fiveregimens: S-1/PTX plus IP PTX, S-1/oxaliplatin plus lP PTX,S-1/cisplatin plus IP PTX, capecitabine/cisplatin plus IP DOC, and FOLFOX plus IP PTX. We performed a phaseII PHOENIX-GC trial comparing S-1/PTX plus IP PTX with S-1/cisplatin.In addition, we retrospectively evaluated the safety and efficacy of gastrectomy.

Results:

In phase l trials, the recommended doses of lPPTX and lP DOC were determined to be 20-40 mg/m2and 10 mg/m2, respectively, with common systemicadverse events.In phasell trials, the 1-year overalsurvival (OS) rate in the FOLFOX plus IP PTX trial inpatients with inadequate oral intake was 56%. Those ofthe other four trials were 72%-78%.The PHOENIX-GC trial narrowly failed to demonstrate statistical superiority of S-1/PTX plus IP PTX over S-1/cisplath.However, the exploratory analysis adjusting for the imbalance in the amount of ascites suggested clinical benefits of lP PTX. Of 222 patients in three multicenter trials, 93 patients underwent gastrectomy after marked shrinkage of peritoneal metastasis.The median OS ofpatients with and without surgery was 26.3 months and 12.3 months, respectively.

Conclusions: 

Multidisciplinary treatment with long-term normothermic lP and systemic chemotherapy is safe and effective for gastric cancer with peritoneal metastasis.

02.2.22-Intraperitoneal+intravenous vs.intravenous paclitaxel+S-1 in gastric cancerwith peritoneal metastasis: Results fromDRAGON-01 trial

Introduction: 

The optimal regimen for gastric cancer with peritoneal metastasis remains undefined.This study assessed the efficacy and safety of intraperitoneal and

intravenous paclitaxel plus S-1 versus intravenous paclitaxel plus S-1 in these patients.

Methodology: 

This phase 3, multicenter, randomized trial involved patients from 9 cancer centers in China.Participants were 18-75 years old with confirmed gastric adenocarcinoma and peritoneal metastases, good performance status, and no prior chemotherapy or

radiotherapy. Patients were randomly assigned (2:1) toeither the NIPS Group (intravenous paclitaxel 50 mg/m2and intraperitoneal paclitaxel 20 mg/m2 on days 1 and 8,plus oral S-1 80 mg/m2 on days 1-14) or the Ps Group(intravenous paclitaxel 70 mg/m2 on days 1 and 8, plus oral S-1 80 mg/m2 on days 1-14).The primary endpoint was overall survival,analyzed using Kaplan-Meier curves and log-rank tests, with Cox regression for multivariate analysis.

Results: 

From May 2017 to March 2022,246 patients were screened, with 222 included in the analysis: 148 in the NlPS Group and 74 in the Ps Group. As of March 2024, median survival was 19.4 months in the NlPS Group and 13.9 months in the PS Group (HR = 0.66; P =0.005).One-year and two-year survival rates were higher in the NIPS Group (69.6% and 37.2% vs.54.1% and20.3%).Common grade 3-4 adverse events included

leukopenia and neutropenia, with no treatment-related deaths.

Conclusions:

intraperitoneal and intravenous paclitaxelplus S-1 significantly improved overall survival in gastric cancer patients with peritoneal metastasis, with manageable toxicity.

02.2.23-Interim results of PlPAC withFOLFOX chemotherapy treatment for gastriccancer with peritoneal metastases Introduction Gastric cancer peritoneal metastases (GCPM) present a significant challenge in oncology, with standard systemic chemotherapy yielding poor outcomes about 20 % with median survival rate from 3 to 9 months.This interim analysis evaluates pressurized intraperitoneal aerosol chemotherapy (PlPAC) combined with FOLFOX as a first-line treatment for GCPM.

Methods

This investigator-initiated, single-arm, phase ll trial investigates PlPAC with cisplatin and doxorubicin followed by systemic FOLFOX. Patients with histologically confirmed GCPM, without prior treatment,are enrolled. Three PlPACs and six FOLFOX cycles are

administered.The primary outcome is the objective response rate (ORR) per REClST v1.1 criteria, with secondary outcomes including morbidity, survival, andquality of life. Simon's two-stage minimax design is used.with 37 anticipated participants.

Results

Between November 2022 and December 2023,20 patients enrolled. 17 completed the treatment, with 1(5%) stopping due to toxicity. ORR after the fourthFOLFOX cycle was achieved in 5 (29.4%) patients.The Peritoneal Cancer Index (PCl) decreased from a median of 14 to 8 by the third PlPAc, though not significantly.Complete histological tumor response (PRGS score 1)increased to 29.4% after the third PlPAC. Negative cytology rise to 47.1%, and the proportion without ascites increased to 70.6%.Two patients underwent RO cytoreductive surgery. After seven months of follow-up，eight patients were alive, and four were progression-free.

Conclusions

Interim results suggest that PlPAC combined with FOLFOXis feasible,well tolerated,and shows promising radiological and histological responses in GCPM patients.

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