Abstract
Single-agent activity for anthracyclines reflected by response rates of 10%–30% has been reported in patients with advanced hepatocellular carcinoma (HCC). Preclinical data indicate that α-interferon could enhance the cytotoxic activity of the anthracycline Adriamycin or its analog epirubicin. In a phase I/II study, 31 patients with biopsy-proven inoperable HCC were treated with interferon-α2b given s. c. at a dose of 3×106 units/m2 per day for 5 days per week plus weekly epirubicin given at 25 mg/m2 as an i. v. bolus. The protocol called for 4 consecutive weeks of treatment followed by 1 week off treatment. In all, 15 patients had been previously treated; 6 patients had failed hormonal therapy (tamoxifen), 5 patients had failed prior anthracycline treatment, and 4 patients had received chemoembolization of the tumor and had subsequently progressed. A total of 30 patients were evaluable for response. In all, 1 patient (3%) achieved a partial response for 8+ months and 11 patients (35%) achieved stabilization of disease. Six patients had a fall in alpha-fetoprotein (AFP) values of >50% during therapy. The median survival for all patients was 9.5 months (range, 3–34+ months). The main side effects were hematological toxicity and fever, both of which were considered tolerable. As an indicator of the immunostimulatory effects of interferon, an elevation in serum markers of inflammation [C-reactive protein (CRP), β2-microglobulin] was found in 15%–20% of patients. All patients had measurable Mx protein production during therapy, but these effects were not correlated to the clinical response. The clinical response rate achieved in this trial indicates that the combination of interferon and epirubicin, at least when used on the schedule reported herein, is not superior to treatment with either agent alone for patients with advanced HCC. However, single patients achieved a prolonged progression-free interval (8–10+ months) on this therapy, and it may therefore be an option for patients who have failed prior hormonal or single-agent anthracycline therapy.
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Bokemeyer, C., Kynast, B., Harstrick, A. et al. No synergistic activity of epirubicin and interferon-α2b in the treatment of hepatocellular carcinoma. Cancer Chemother. Pharmacol. 35, 334–338 (1995). https://doi.org/10.1007/BF00689454
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DOI: https://doi.org/10.1007/BF00689454