title: Low serum alpha-fetoprotein level in patients with hepatocellular carcinoma as a predictor of response to 5-FU and interferon-alpha-2b.
abstract: BACKGROUND
  A Phase II clinical trial was conducted to evaluate the efficacy of intravenous fluorouracil (5-FU) and subcutaneous recombinant interferon-alpha-2b (rIFN-alpha-2b) in the treatment of hepatocellular carcinoma (HCC) and to define factors that might be predictive of a response to treatment.
  
  
  METHODS
  Twenty-nine patients were registered on the protocol. 5-FU was administered as a continuous intravenous (i.v.) infusion (dose = 750 mg/m2) for 5 consecutive days. rIFN-alpha-2b was administered subcutaneously (SC) (dose = 5 x 10(6) um/m2) once a day on days 1, 3, and 5 of the 5-FU infusion. The treatment was repeated at 14-day intervals. Responses were assessed at the end of one course of therapy, which was equivalent to four treatments.
  
  
  RESULTS
  Of the 28 patients evaluable for response, 5 (18%) had a partial response, and 1 (4%) had a minor response. Responses lasted from more than 2 to more than 24 months (median, 11.5 months). Ten (36%) patients experienced no response, and 12 (43%) had progressive disease. The 6 responders were part of a group of 16 patients who had pretreatment levels of serum alpha-fetoprotein (AFP) of 50 ng/ml or less and a group of 8 whose tumors involved 50% or less of the liver parenchyma. Mucositis, which occurred in 54% of the patients, was the most common toxicity associated with the treatment regimen. Diarrhea and dermatitis were observed in 16% and 17% of the patients, respectively; fatigue, thrombocytopenia, granulocytopenia, neurologic toxicity, and nausea and vomiting were not commonly seen.
  
  
  CONCLUSIONS
  The regimen of i.v. 5-FU and SC rIFN-alpha-2b was well tolerated and induced durable partial response in 31% (5 of 16) of patients with HCC who had low levels of serum AFP and in those with 50% or less of liver replacement. In contrast, the treatment regimen was ineffective in patients with HCC who had high levels of serum AFP or extensive liver disease.
authors.affiliation: Department of Gastrointestinal Medical Oncology and Digestive Diseases, University of Texas M.D. Anderson Cancer Center, Houston 77030.
authors.forename: Y Z
authors.initials: YZ
authors.lastname: Patt
authors.forename: B
authors.initials: B
authors.lastname: Yoffe
authors.forename: C
authors.initials: C
authors.lastname: Charnsangavej
authors.forename: R
authors.initials: R
authors.lastname: Pazdur
authors.forename: H
authors.initials: H
authors.lastname: Fischer
authors.forename: K
authors.initials: K
authors.lastname: Cleary
authors.forename: M
authors.initials: M
authors.lastname: Roh
authors.forename: R
authors.initials: R
authors.lastname: Smith
authors.forename: C A
authors.initials: CA
authors.lastname: Noonan
authors.forename: B
authors.initials: B
authors.lastname: Levin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000628:therapy*; D017024:Chemotherapy, Adjuvant; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000627:therapeutic use; D012074:Remission Induction; D016019:Survival Analysis; D000509:alpha-Fetoproteins / Q000032:analysis*
chemical_list: D015415:Biomarkers; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D000509:alpha-Fetoproteins; D005472:Fluorouracil