Intraperitoneal chemotherapy in the treatment of gastric cancer peritoneal metastases: An overview of common therapeutic regimens

Abstract

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.