title: 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.
abstract: 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.
  
  
  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/m2/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 patient). Moreover, one patient developed fatal ischemic stroke and another a fatal central venous catheter infection.
  
  
  CONCLUSIONS
  The preliminary data, show that an interferon-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.
authors.affiliation: Division of Medical Oncology, San Vincenzo Hospital Taormina, Italy. vitale.dr.felice@tiscali.it
authors.forename: Felice Vito
authors.initials: FV
authors.lastname: Vitale
authors.forename: Placido
authors.initials: P
authors.lastname: Romeo
authors.forename: Fabio
authors.initials: F
authors.lastname: Vasta
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Panebianco
authors.forename: Stefania
authors.initials: S
authors.lastname: Calì
authors.forename: Stefano
authors.initials: S
authors.lastname: Rotondo
authors.forename: Francesco
authors.initials: F
authors.lastname: Ferraù
authors.forename: Michele
authors.initials: M
authors.lastname: La Greca
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000276:immunology / Q000628:therapy*; D003131:Combined Modality Therapy; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D007261:Infusions, Intra-Arterial; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000009:adverse effects; D008113:Liver Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011994:Recombinant Proteins
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D005472:Fluorouracil