A PHASE-II STUDY OF MITOXANTRONE COMBINED WITH INTERFERON-BETA IN UNRESECTABLE HEPATOCELLULAR-CARCINOMA

Background. Chemoimmunotherapy is being evaluated in the most common g astrointestinal tumors, but little data are available on hepatocellula r carcinoma (HCC). Considering the encouraging objective response rate s and the absence of important side effects obtained with mitoxantrone in HCC, we tested the activity and feasibility of a schedule combinin g beta-interferon (beta-IFN) and mitoxantrone. Methods. Forty patients (ECOG Performance Status 0-1) with unresectable HCC received mitoxant rone (12 mg/m2 intravenously every 3 weeks) plus beta-IFN (3 x 10(6) U on days 1, 2, and 3; 6 X 10(6) U from day 4 to day 60; and then 6 X 1 0(6) U three times a week for 10 months). Results. Thirty-eight patien ts were evaluable for response and toxicity with a median of four admi nistered cycles (range, 2-10 cycles). Nine patients achieved a partial response (23%) (95% confidence interval, 11-40%) with a median durati on of response of 4 months. In 15 cases, the disease was stable for at least 2 months; 14 patients had disease progression. The median survi val time of the group as a whole was 8 months. Patients who were alpha -fetoprotein positive had a median survival time of 7 months; those wh o were alpha-fetoprotein negative had a median survival time of 9 mont hs. The most common side effects were hematologic (World Health Organi zation Grade 3, 15 patients; Grade 4, 3 patients). Mild or moderate fl ulike syndrome was present in 50% of treated patients, whereas 10 pati ents experienced mild or moderate nausea. Conclusions. The schedule wa s active on advanced tumors with high alpha-fetoprotein values, and si de effects were manageable. However, the addition of beta-IFN did not seem to improve significantly the response rate in HCC.