Hepatic intra-arterial interferon alpha 2b-based immunotherapy combined with 5-fluorouracil (5-FU)-based systemic chemotherapy for patients with hepatocellular carcinoma (HCC) not responsive and/or not eligible for conventional treatments: a pilot study.

Background: Surgery (partial hepatic resection or orthotopic liver transplantation) remains the mainstay for treatment of hepatocellular carcinoma (HCC). Unfortunately, most patients have HCC that cannot be removed either as a result of its size, multiple tumors, location, proximity to major vessels or ducts within the liver, and comorbidity, such as a not well-compensated cirrhosis. For patients who cannot be treated surgically, systemic chemotherapy is frequently limited by unacceptable toxicity, poor response and low survival rates, so that locoregional approaches may be considered as alternatives. Patients and Methods: Nine patients with HCC, not eligible for conventional treatments, were treated with interferon alpha 2b-based locoregional, hepatic intra-arterial, immunotherapy and concomitant 5-fluorouracil (5-FU)-based systemic chemotherapy. Interferon was administered at a starting dose of 2,000,000 IU which could be escalated to 9,000,000 IU adding 1,000,000 IU weekly, depending on toxicity. 5-Fluorouracil was infused continuously over 28 days, administered as an endovenous protracted infusion weekly at a dose of 250 mg/m 2 /day for 4 weeks followed by a 2-week break. Eight out of nine patients were evaluable for response and toxicity. The median patient age was 68 years (range 51-77 years). All patients were suffering from cirrhosis. Results: A total of 29 cycles of treatment were administered with a median of 3.6 per patient range (1-11 per patients). A partial response was observed in 3 out of 8 patients; 1 had stable and 4 progressive disease. The main toxicities were: grade 3 hepatic toxicity (1 patient), grade 3 flu-like syndrome (1 patient) and grade 3 abdominal pain (1 patients). Moreover, one patient developed fatal ischemic stroke and another a fatal central venous catheter infection. Concmusion: The preliminary data, show that an ointerferon-based hepatic intra-arterial immunotherapy combined with low doses of 5―fluorouracil (5―FU)-based systemic chemotherapy, can represent a tolerable combination to apply in the palliative treatment of patients with hepatocellular carcinoma.