Prolonged intraperitoneal infusion of 5-fluorouracil using a novel carrier solution

Area of Science:

• Oncology
• Pharmacology
• Medical Devices

Background:

• Peritoneal carcinomatosis presents treatment challenges.
• Intraperitoneal chemotherapy offers localized drug delivery.
• Novel carrier solutions enable new administration methods.

Purpose of the Study:

• To determine the toxicities and maximum tolerated dose of prolonged intraperitoneal 5-fluorouracil (5-FU) infusion.
• To evaluate the pharmacokinetics of continuous intraperitoneal 5-FU.
• To assess the feasibility of using Icodextrin 20 as a peritoneal carrier solution.

Main Methods:

• Phase I pharmacokinetic study involving 17 patients with peritoneal carcinomatosis.
• Tenckhoff catheter placement for intraperitoneal drug administration.
• Daily intraperitoneal 5-FU (5 days/week) via bolus and continuous infusion for 12 weeks, using Icodextrin 20.

Main Results:

• Abdominal pain and infective peritonitis were the primary dose-limiting toxicities.
• Redesign of the delivery system mitigated peritonitis, allowing a dose of 300 mg m-2 5-FU daily.
• Achieved high intraperitoneal 5-FU concentrations (mean 47,500 ng/mL) compared to systemic levels (mean 30 ng/mL).

Conclusions:

• Prolonged intraperitoneal 5-FU infusion is feasible with Icodextrin 20.
• High peritoneal drug concentrations were achieved, exceeding systemic levels significantly.
• Further investigation into the efficacy of this treatment for peritoneal carcinomatosis is warranted.