Low serum alpha‐fetoprotein level in patients with hepatocellular carcinoma as a predictor of response to 5‐fu and interferon‐alpha‐2b

Background. A Phase II clinical trial was conducted to evaluate the efficacy of intravenous fluorouracil (5‐FU) and subcutaneous recombinant interferon‐alpha‐2b (rIFN‐α‐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 (IV) infusion (dose = 750 mg/m²) for 5 consecutive days. rIFN‐α‐2b was administered subcutaneously (SC) (dose = 5 × 10⁶ 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, thrombo‐cytopenia, granulocytopenia, neurologic toxicity, and nausea and vomiting were not commonly seen. Conclusions. The regimen of IV 5‐FU and SC rIFN‐α‐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 in effective in patients with HCC who had high levels of serum AFP or extensive liver disease.