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

Cancer. 1993 Dec 1;72(11):3196-201. doi: 10.1002/1097-0142(19931201)72:11<3196::aid-cncr2820721111>3.0.co;2-q.

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 (beta-IFN) and mitoxantrone.

Methods: Forty patients (ECOG Performance Status 0-1) with unresectable HCC received mitoxantrone (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) from day 4 to day 60; and then 6 x 10(6) 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 flu-like 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 beta-IFN did not seem to improve significantly the response rate in HCC.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase II

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / pathology
  • Carcinoma, Hepatocellular / therapy*
  • Chemoembolization, Therapeutic
  • Drug Administration Schedule
  • Feasibility Studies
  • Female
  • Humans
  • Injections, Intramuscular
  • Injections, Intravenous
  • Interferon-beta / administration & dosage
  • Interferon-beta / adverse effects
  • Interferon-beta / therapeutic use*
  • Leukopenia / chemically induced
  • Leukopenia / etiology
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / pathology
  • Liver Neoplasms / therapy*
  • Male
  • Middle Aged
  • Mitoxantrone / administration & dosage
  • Mitoxantrone / adverse effects
  • Mitoxantrone / therapeutic use*
  • Remission Induction
  • Survival Rate
  • Thrombocytopenia / chemically induced
  • Thrombocytopenia / etiology

Substances

  • Interferon-beta
  • Mitoxantrone