Brandl Andreas, Prabhu Aruna
Digestive Unit, Champalimaud Foundation, Lisbon, Portugal.
Department of Surgical Oncology, Thangam Cancer Center, Namakkal, Tamil Nadu, India.
J Gastrointest Oncol. 2021 Apr;12(Suppl 1):S32-S44. doi: 10.21037/jgo-2020-04.
Peritoneal metastasis (PM) have an incidence of 10-20% in patients with gastric cancer (GC), and even up to 40% in patients with UICC Stage III GC. Due to the aggressive characteristic of adenocarcinoma of the stomach, GC is the third leading cause of cancer deaths worldwide. For GC with PM, the treatment of choice is according to national and international guidelines systemic chemotherapy, combined with biologic therapy against specific receptor antigen in with overexpression, such as HER-2. Multimodal treatment regimens including intraperitoneal application of chemotherapy and cytoreductive surgery (CRS) have been investigated and established all over the world. Driven by pharmacological studies and thoughts considering the increased benefits of cytotoxic agents used in the abdominal cavity, several drugs and drug combinations are widely used. In order to standardize treatment protocols, it is crucial to differentiate between normothermic and hyperthermic intraperitoneal chemotherapy (NIPEC, HIPEC). The requirements of an ideal cytotoxic drug different obviously dependent on its application method. Because of their high molecular weight and lipophilic structure, taxanes, such as paclitaxel or docetaxel have a long intraperitoneal retention time and are commonly used in NIPEC, while platin derivates, such as carboplatin or oxaliplatin are known for their synergistic effect to heat and are chosen in HIPEC. This review aims to explore and summarize different intraperitoneal treatment regimens strictly evaluated by supporting evidence in an effort to consolidate many regimens to a few evidence-based treatment protocols that deserve further investigation and distribution. This analysis included all studies focusing on intraperitoneal chemotherapy: Phase II, Phase III trials and non-randomized retrospective trials of larger cohorts of patients with GC and established PM or risk of PM. Interestingly, the protocols for NIPEC are quite uniform, with less variation between the therapeutic components in contrast to the different HIPEC protocols. This difference might be explained by the divergent evolution of NIPEC and HIPEC, as the former exclusively originated in Japan, while HIPEC experienced a more multicentric evolution and distribution in the United States, Asia, Europe, and worldwide utilization today.
腹膜转移（PM）在胃癌（GC）患者中的发生率为10%-20%，在国际抗癌联盟（UICC）III期GC患者中甚至高达40%。由于胃腺癌具有侵袭性，GC是全球癌症死亡的第三大主要原因。对于伴有PM的GC，治疗选择是根据国家和国际指南进行全身化疗，并联合针对过表达的特定受体抗原的生物治疗，如HER-2。包括腹腔内化疗和细胞减灭术（CRS）在内的多模式治疗方案已在全球范围内进行了研究和确立。受药理学研究以及考虑到腹腔内使用细胞毒性药物益处增加的思路驱动，几种药物和药物组合被广泛使用。为了规范治疗方案，区分常温与热灌注腹腔内化疗（NIPEC、HIPEC）至关重要。理想细胞毒性药物的要求因其应用方法的不同而有明显差异。由于紫杉烷类药物（如紫杉醇或多西他赛）分子量高且具有亲脂性结构，在腹腔内保留时间长，常用于NIPEC，而铂类衍生物（如卡铂或奥沙利铂）以其对热的协同作用而闻名，被选用于HIPEC。本综述旨在探索和总结不同的腹腔内治疗方案，并通过支持性证据进行严格评估，以便将多种方案整合为一些值得进一步研究和推广的循证治疗方案。该分析纳入了所有聚焦于腹腔内化疗的研究：II期、III期试验以及GC伴已确立的PM或有PM风险的较大患者队列的非随机回顾性试验。有趣的是，NIPEC的方案相当统一，与不同的HIPEC方案相比，治疗成分之间的差异较小。这种差异可能是由于NIPEC和HIPEC的发展路径不同，前者仅起源于日本，而HIPEC经历了更多的多中心发展，并在美国、亚洲、欧洲以及如今在全球范围内得到应用。
