Hepatic arterial chemotherapy with oxaliplatin, folinic acid and 5-fluorouracil in pre-treated patients with liver metastases from colorectal cancer.

BACKGROUND: Hepatic arterial chemotherapy (HAC) is an effective treatment of liver metastases from colorectal cancer (CRC). Phase I and II studies have already shown the feasibility and efficacy of intra-arterial oxaliplatin (OXA). PATIENTS AND METHODS: Twenty-one pre-treated patients with liver metastases who received HAC with OXA/folinic acid (FA)/5-fluorouracil (5-FU) at our Division between March 2000 and November 2003, were clinically examined. Most patients were heavily pre-treated with two or more systemic chemotherapeutic regimes. All patients received a percutaneously implanted catheter into the hepatic artery through femoral or transaxillary access. Treatment was administered every 14 days: OXA 100 mg/m2 as a 12-hour infusion on day 1; FA 100 mg/m2 as a 2-hour infusion on days 2 and 3; 5-FU 2600 mg/m2 as a continuous infusion on days 2 and 3. RESULTS: Grade 3-4 toxicities were: asthenia (2 out of 21), transaminase elevation (2 out of 21) and pain (2 out of 21), nausea and vomiting (1 out of 21), neutropenia (1 out of 21), thrombocytopenia (1 out of 21) and neurotoxicity (1 out of 21). Main dose limiting toxicity was right upper quadrant pain. Response rates were: 5% complete response, 19% partial response, 28% stable disease and 48% progressive disease. Two patients became operable and underwent complete resection of liver disease. The median overall survival was 36.1 months. Two-year and 3-year survival rates were 62% and 52%, respectively. CONCLUSION: This regimen is feasible with low toxicity and with an encouraging overall tumor growth control (52%) in a subset of heavily pre-treated patients. Intra-arterial OXA/FA/5-FU should be considered for the treatment of patients pre-treated with systemic chemotherapies with liver metastases from CRC.

Phase II study of hepatic intraarterial epirubicin and cisplatin, with systemic 5-fluorouracil in patients with unresectable biliary tract tumors.

BACKGROUND: Patients with unresectable biliary tract carcinomas have a very poor prognosis. To improve the efficacy and tolerance of the ECF regimen (epirubicin at a dose of 50 mg/m2, cisplatin at a dose of 60 mg/m2, and 5-fluorouracil [5-FU] at a dose of 200 mg/m2 per day by continuous infusion), the authors designed a novel approach that combined locoregional and systemic chemotherapy with the same agents at the same dosages. METHODS: Thirty consecutive patients with advanced or metastatic biliary tumors were treated with epirubicin at a dose of 50 mg/m2 and cisplatin at a dose of 60 mg/m2 administered as a bolus in the hepatic artery on Day 1, combined with systemic continuous infusion of 5-FU at a dose of 200 mg/m2 per day, from Day 1 to Day 14, every 3 weeks. RESULTS: Tumor sites were the intrahepatic bile ducts in 25 patients and the gallbladder in 5 patients. The overall response rate was 40% (12 of 30 patients), including 1 complete response and 11 partial responses. Stable disease was observed in 12 of 30 patients (40%) and progressive disease in 6 of 30 patients (20%). The median progression-free and overall survival periods were 7.1 and 13.2 months, respectively, and the 1-year and 2-year survival rates were 54% and 20%, respectively. Performance status improved in 9 of 30 patients (30%) and a weight gain of > 7% was observed in 4 of 30 patients (13%). The treatment was well tolerated with minimal hematologic toxicity. The major clinical problem was the deep venous thrombosis related to the central venous catheter, which occurred in 5 patients (17%). CONCLUSIONS: This novel combined locoregional and systemic chemotherapeutic regimen was found to be active and safe for patients with advanced biliary tract carcinoma.