ISOLATED LIVER PERFUSION WITH MITOMYCIN-C IN THE TREATMENT OF COLORECTAL-CANCER METASTASES CONFINED TO THE LIVER

We evaluated the technical feasibility of isolated liver perfusion (IL P) in the treatment of patients with colorectal cancer metastases conf ined to the liver, and investigated whether ILP allows exposure of the tumor to high concentrations of mitomycin C (MMC). Furthermore, survi val time and tumor response were studied. Nine patients were treated w ith 30 mg/m(2) MMC recirculated for one hour in the isolated circuit. The MMC concentration in the perfusate and plasma was measured using a high-performance liquid chromatography assay. All complications direc tly related to the surgical procedure were treated effectively (no mor tality). The peak concentration of MMC in the perfusate was 5 to 11 ti mes higher than that measured in the plasma of patients treated with 2 0 to 60 mg/m(2) MMC i.v., and the concentration remained significantly higher during the whole perfusion period. In contrast, the peak conce ntration of MMC in plasma was approximately two thirds of the lowest p eak plasma level measured after i.v. administration of 10 mg/m(2) MMC. No systemic toxicity was observed in any of our patients. However, fo ur patients developed veno-occlusive disease of the liver which was mi ld in three but lethal in one. One of the eight evaluable patients had an objective complete response (25 months), one an objective partial response and five others a clear reduction in tumor size (25-50%). The median survival time was 17 months. This study demonstrates that ILP is technically feasible in patients, and in comparison with systemic t herapy allows exposure of hepatic metastases to much higher concentrat ions of MMC, while systemic toxicity is absent. Remarkably, this singl e exposure to a high concentration of MMC resulted in a complete respo nse and a median survival time comparable to that in recently publishe d hepatic artery infusion studies with floxuridine and leucovorin. How ever, due to the hepatotoxicity we are continuing our studies with mel phalan to further exploit the possible therapeutic benefit of ILP.