Low Serum Alpha-Fetoprotein Level in Patients With Hepatocellular Carcinoma as a Predictor of Response to 5-FU and interferon-alpha-2b

Cancer. 1993 Nov 1;72(9):2574-82. doi: 10.1002/1097-0142(19931101)72:9<2574::aid-cncr2820720911>3.0.co;2-l.


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.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Biomarkers / blood
  • Carcinoma, Hepatocellular / blood
  • Carcinoma, Hepatocellular / therapy*
  • Chemotherapy, Adjuvant
  • Female
  • Fluorouracil / administration & dosage
  • Fluorouracil / therapeutic use*
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / administration & dosage
  • Interferon-alpha / therapeutic use*
  • Male
  • Middle Aged
  • Recombinant Proteins / therapeutic use
  • Remission Induction
  • Survival Analysis
  • alpha-Fetoproteins / analysis*


  • Biomarkers
  • Interferon alpha-2
  • Interferon-alpha
  • Recombinant Proteins
  • alpha-Fetoproteins
  • Fluorouracil