Rationale for the administration of systemic 5-FU in combination with heated intraperitonal oxaliplatin

Area of Science:

• Oncology
• Surgical Oncology
• Pharmacology

Background:

• Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) using oxaliplatin (OX) is standard for colorectal carcinomatosis.
• Intravenous (IV) 5-fluorouracil (5-FU) improves OX efficacy systemically, leading to empirical combination with HIPEC OX.
• Preclinical data is lacking to support the combination of IV 5-FU with HIPEC OX.

Purpose of the Study:

• To investigate the impact of IV 5-FU on the peritoneal absorption of HIPEC OX in a preclinical model.
• To determine the optimal dose of IV 5-FU for enhancing HIPEC OX peritoneal delivery.

Main Methods:

• 24 Sprague-Dawley rats received varying doses of IV 5-FU (0-800 mg/m²) and a fixed dose of HIPEC OX (460 mg/m²) at 40°C for 25 minutes.
• Peritoneal, portal vein, and systemic blood samples were collected post-perfusion.
• High-performance liquid chromatography (HPLC) measured 5-FU and OX concentrations.

Main Results:

• Peritoneal OX absorption significantly increased with higher IV 5-FU doses (p < 0.0001).
• Absorption of OX plateaued between 400 and 800 mg/m² of IV 5-FU.
• Specific absorption values ranged from 17.0 to 38.1 nmol/g with increasing 5-FU doses.

Conclusions:

• IV 5-FU administration enhances the peritoneal absorption of oxaliplatin during HIPEC.
• An IV 5-FU dose of 400 mg/m² is suggested as the most effective for combination therapy with HIPEC OX.