A phase II study of mitoxantrone combined with beta-interferon in unresectable hepatocellular carcinoma

Abstract

Background. Chemoimmunotherapy is being evaluated in the most common gastrointestinal tumors, but little data are available on hepatocellular carcinoma (HCC). Considering the encouraging objective response rates and the absence of important side effects obtained with mitoxantrone in HCC, we tested the activity and feasibility of a schedule combining beta‐interferon (β‐IFN) and mitoxantrone. Methods. Forty patients (ECOG Performance Status 0‐1) with unresectable HCC received mitoxantrone (12 mg/m2 intravenously every 3 weeks) plus β‐IFN (3 × 106 U on days 1, 2, and 3; 6 × 106 U from day 4 to day 60; and then 6 × 106 U three times a week for 10 months). Results. Thirty‐eight patients were evaluable for response and toxicity with a median of four administered cycles (range, 2–10 cycles). Nine patients achieved a partial response (23%) (95% confidence interval, 11–40%) with a median duration of response of 4 months. In 15 cases, the disease was stable for at least 2 months; 14 patients had disease progression. The median survival 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 who were alpha‐fetoprotein negative had a median survival time of 9 months. The most common side effects were hematologic (World Health Organization Grade 3, 15 patients; Grade 4, 3 patients). Mild or moderate flulike syndrome was present in 50% of treated patients, whereas 10 patients experienced mild or moderate nausea. Conclusions. The schedule was active on advanced tumors with high alpha‐fetoprotein values, and side effects were manageable. However, the addition of β‐IFN did not seem to improve significantly the response rate in HCC.

Antiviral therapy after non‐surgical tumor ablation in patients with hepatocellular carcinoma associated with hepatitis C virus

“…16 Interferon has been found to have antiviral, anticarcinogenic, and immunostimulant activities. [25][26][27] Some investigators showed that IFN acted as an anticancer agent in the treatment of HCC in vivo and in vitro. 26,27 In the present study we showed that the benefits of preventing tumor recurrence and prolonging survival were observed in patients with SR, whereas non-responders had a similar clinical outcome as compared with control patients.…”

Combination therapy with transarterial chemoembolization and interferon‐α compared with transarterial chemoembolization alone for hepatitis B virus related unresectable hepatocellular carcinoma

“…Interferon‐alpha (IFN‐α) has immunomodulatory, antiviral, antiproliferative, and antitumoral effects 14–16 . It is effective in treating hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, improving the prognosis of patients with chronic liver disease, reducing cirrhosis or HCC development, and prolonging survival 17–20 .…”

Long–Term Beneficial Effect of Interferon Therapy in Patients With Chronic Hepatitis B Virus Infection

“…Interferon (IFN) has antiviral, immunomodulatory, antitumoral, and antiproliferative effects. [1][2][3] The aims of IFN therapy for chronic hepatitis B virus (HBV) infection are to eradicate HBV, to halt hepatic necroinflammation, and to prevent or reduce the risk of cirrhosis and hepatocellular carcinoma (HCC) development. 4 It is generally agreed that IFN therapy is effective in 30% to 40% of the patients with chronic HBV infection in terms of virological and histological remission.…”