Pharmacokinetic of intraarterial mitomycin C with extra corporeal detoxification in humans

Purpose: A study has been performed in 15 patients with liver metastases from colorectal cancer to evaluate the pharmacokinetic of mitomycin C and the effectiveness of drug removal techniques during high-dose locoregional chemotherapy. Patients and Methods: Haemofiltration and/or haemodialysis of post-hepatic venous blood were performed during 22 intraarterial infusions of mitomycin C by the use of a double lumen catheter surgically introduced in the inferior vena cava. Mitomycin C levels were measured by high performance liquid chromatography in the extracorporeal circuit blood, in the peripheral venous blood and ultrafiltrate. Results: The mean reduction of mitomycin C bioavailability in the extracorporeal circuit blood was 42.3 per cent using haemofiltration, 58.9 per cent using haemofiltration plus haemodialysis and 59.3 per cent with haemodialysis alone. The resulting mean mitomycin C plasmatic half-life was 40.2 minutes using haemofiltration, 24.9 minutes using haemofiltration plus haemodialysis and 24.1 minutes using haemodialysis alone. Conclusions: The detoxification of posthepatic venous blood during intra-arterial hepatic chemotherapy is an effective method to increase mitomycin C concentrations and oncological response and limit extra hepatic toxicity.