Discussion
peritoneal disease, toxicity
PERITONEAL DISEASE
In this study, we aim to investigate the combination of PIPAC (cisplatin and doxorubicin) and systemic FOLFOX chemotherapy efficacy for the first-line treatment of GC PM.We designed this study, because of several reasons. First, novel treatment strategies for GC PM are urgently needed as conventional methods (systemic therapy) have only a very limited efficacy with a median OS ranging between 2 and 9 months [Second, there is some evidence indicating the potency of PIPAC. A recent systematic review summarized current evidence and suggested that PIPAC can lead to improved long-term outcomes with a median OS of 8-19.1 months [The primary outcome of the present study is objective response rate (ORR) according to RECIST v. 1.1 criteria [To our best knowledge several other clinical studies investigating bidirectional PIPAC as a first-line treatment of GC PM are currently undergoing (NCT05318794; NCT04913662; NCT05303714). SPECTRA (NCT05318794) single-arm study is investigating the feasibility and safety of 3 cycles of standard systemic chemotherapy interposed with 3 PIPAC (Doxorubicin and Cisplatin) sessions for patients with limited peritoneal disease (PCI ≤ 3) in the United Kingdom. Another phase I study undergoing in South Korea (NCT04913662) investigates dose-limiting toxicity of PIPAC (Paclitaxel) and Systemic FOLFOX combination for GC PM. And finally, there is already a phase III randomized control trial (PIPAC_VEROne; NCT05303714) undergoing in Italy. This study randomizes patients with GC PM to 6 cycles of FOLFOX or 6 cycles of FOLFOX with 3 PIPACs (Doxorubicin and Cisplatin) performed every two cycles of chemotherapy. PIPAC_VEROne study treatment protocol is very similar to the present study. However, different from our study, the Italian trial will include only patients with the limited peritoneal disease (PCI ≤ 6).Thus, our study will be the first to provide knowledge of PIPAC and FOLFOX efficacy for GC patients with PM, including those with higher PCI scores.