[Fundamental study on intra-arterial chemotherapy with direct hemoperfusion]

Area of Science:

• Oncology
• Pharmacology
• Nephrology

Background:

• Intra-arterial chemotherapy is a treatment for bladder cancer.
• Systemic toxicity is a significant concern with anti-neoplastic agents.
• Direct hemoperfusion (DHP) is a potential method to mitigate drug toxicity.

Purpose of the Study:

• To compare the pharmacokinetics of Cis-platinum (CDDP), Mitomycin C (MMC), and Doxorubicin hydrochloride (ADM) during intra-arterial chemotherapy with and without DHP in a canine model.
• To evaluate the efficacy of DHP in reducing systemic drug exposure and potential renal toxicity.

Main Methods:

• Canine subjects received intra-arterial chemotherapy with CDDP, MMC, or ADM.
• One group underwent simultaneous DHP during chemotherapy infusion, while the control group did not.
• Blood drug concentrations, cartridge clearance rates, and urinary drug recovery were measured.

Main Results:

• DHP significantly reduced peripheral blood drug concentrations for all three agents compared to controls.
• DHP cartridges demonstrated high clearance rates for MMC and ADM, and initially for CDDP.
• Urinary recovery of CDDP was lower with DHP, indicating significant adsorption by the DHP cartridges (48.3% of the dose).

Conclusions:

• Simultaneous DHP with intra-arterial chemotherapy is effective in reducing systemic exposure to CDDP, MMC, and ADM.
• DHP shows promise in mitigating the renal toxicity associated with these anti-cancer drugs.
• Optimal efficacy is achieved when DHP is employed concurrently with chemotherapy throughout the entire infusion period.