Hepatic artery infusion of 5-fluorouracil, folinic acid plus oxaliplatin for liver metastasis from colorectal cancer. Final analysis of a phase I/II studay

Abstract

3628 Objective: Numerous studies and meta-analyses have shown significantly higher response rates of hepatic artery infusion (HAI) compared to systemic chemotherapy for liver metastasis from colorectal cancer (CRC). The combination of oxaliplatin with 5-FU and folinic acid can be safely administered as HAI. This final analysis of a phase I-/II-study evaluates toxicity and efficacy of this intraarterial regimen. Methods: Patients with histologically documented CRC with exclusive liver metastasis after surgery of the primary tumor were included. Pts received HAI with folinic acid (200mg/m2, 1 hour infusion) followed by 5-FU (600mg/m2, 2 hour infusion) on days 1 to 5, combined with oxaliplatin (62,5mg/m2, 4 hour infusion) on days 2 and 4. As a long term intrahepatic access, a chamber device was implanted into the groin connected to a catheter radiologically placed into the hepatic artery. Supportive treatment consisted of a 5-HT3-receptor antagonist p.o., paracetamol 1000mg p.o. and a H2-antagonist. Furthermore dexamethasone 8mg p.o. was given 30 min prior and 2 hours after application of oxaliplatin. Results: Twenty-four pts were enrolled (66% colon cancer, 34% rectum cancer). Median age was 62 years (range 34–77), ECOG PS≤2. They were either chemonaive (n=14) or had received an adjuvant treatment ≥6 months before start of study (n=10). Median number of HAI cycles was 7 (range 2–26). WHO grade 3/4-toxicities included leucopenia (19%), thrombocytopenia (10%), hyperbilirubinemia (10%), diarrhea (5%), and abdominal pain (10%). The overall response rate was 70,8%. Complete remission was observed in 5 pts (20,8%), PR in 12 pts (50%), 3 pts obtained SD (12,5%), and 4 had PD (16,7%). Median TTP was 8,8 months. Median overall survival reached 25,5 months. Four years after start of treatment, 5 pts (20,8%) were alive. Two pts (8,3%) had obtained partial liver resection, and 2 pts (8,3%) were treated with radiofrequency ablation after remission had been achieved by the intrahepatic chemotherapy. Conclusion: This final analysis indicates that HAI of 5-FU, folinic acid and oxaliplatin is safe and highly effective in patients with exclusive liver metastasis from CRC. No significant financial relationships to disclose.