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Aims Twenty-three patients with liver metastases from colorectal cancer were entered into a prospective, phase II pilot study to evaluate the efficacy and feasibility of intra-arterial high-dose chemoterapy (IAHC) + intraperitoneal chemotherapy (IPC) combined with hemofiltration. Methods All patients had abdominal laparotomy to position a hepatic artery infusion port and in 15 cases an implantable system for IPC. A double-lumen filtration catheter was placed in the vena cava via the saphenous or femoral vien and connected to a modified hemofiltration unit. The treatment schedule consisted of mitomycin (30-50 mg/m2) and epirubicin (60-90) mg/m2) as IAHC combined with cisplatin (60 mg/m2) given in a 2000 ml saline solution by IPC. The high-dose IAHC-IPC was followed by 4 cycles of intra-arterial standard dose chemotherapy through the arterial port-a-cath (6 mg/m2 mitomycin and 20 mg/m2 epirubicin) and if possible by another cycle of high dose IAHC-IPC. Results We delivered a toal of 31 cycles of IAHC, 21 of which were combined with IPC. Ten cycles of IAHC were administered without concurrent IPC because of painful adhesions, clinical contraindications or patient refusal. Seven of 23 patients (30%) were pretreated and with progressive disease after systemic chemotherapy. Among 22 evaluable patients, we obtained 2 complete remissions (9%) and 11 partial remissions (50%); moreover, 4 of 7 pretreated patients obtained a response to treatment. As a result, an objective tumor response was observed in 59% of patients (13/22). Therefore, a dose-response behavior was demonstrated also in tumors with a low chemosensitivity. The median duration of response and survival was 10 and 14 months, respectively. Toxicity was usually mild, but we reported one toxic death due to treatment complications. Conclusions Further prospective randomized studies are needed to confirm the results of our study.