Normothermic Intraperitoneal and Systemic Treatment (NIPS) Using Paclitaxel for Peritoneal Metastases from Gastrointestinal Cancer

Peritoneal metastasis (PM) is the most frequent and lethal pattern of dissemination in gastrointestinal malignancies. Despite advances in systemic chemotherapy, outcomes remain poor because the unique biology of PM, characterized by poor vascularization and the peritoneal–plasma barrier (PPB), limits drug penetration and contributes to treatment resistance. To address these challenges, several locoregional treatment strategies have been developed, including cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) and pressurized intraperitoneal aerosol chemotherapy (PIPAC). However, their widespread adoption is constrained by invasiveness, strict patient selection, and inconsistent survival benefits. Normothermic intraperitoneal and systemic treatment (NIPS) has emerged as a practical and less invasive alternative, particularly in East Asia. Through an implanted intraperitoneal port, NIPS enables repeated drug administration, providing sustained regional exposure while imposing minimal procedural burden. Importantly, it can be readily integrated with systemic chemotherapy, making it suitable for long-term multimodal treatment. Among available agents, paclitaxel (PTX) is particularly well suited for intraperitoneal administration because of its prolonged retention within the peritoneal cavity and limited systemic absorption. These pharmacokinetic properties allow high local drug concentrations with relatively low systemic toxicity. Consequently, PTX-based NIPS represents a biologically rational and clinically feasible treatment strategy for PM. This review summarizes the pharmacological rationale, clinical evidence, and emerging innovations in drug formulation and delivery that may further enhance the efficacy of PTX-based intraperitoneal chemotherapy for this challenging disease.