Objective: The aim was to determine the recommended dose of combined chemotherapy with mitoxantrone and uracil/tegafur (Phase I part) and to clarify its efficacy and safety in patients with advanced hepatocellular carcinoma at the recommended dose (Phase II part).
Methods: Patients eligible had histologically confirmed, chemo-naive advanced hepatocellular carcinoma and were amenable to established forms of treatment. The therapy consisted of mitoxantrone administered intravenously at one of three dosages (6, 8 and 10 mg/m(2)/day) on day 1 and uracil/tegafur administered orally at 300 mg/m(2) from day 1 through day 21. The treatment was repeated every 4 weeks until evidence of tumor progression or unacceptable toxicity.
Results: A total of 25 patients were enrolled. In the Phase I part, dose-limiting toxicities occurred in all three patients, given mitoxantrone at the dosage of 10 mg/m(2)/day, and the recommended mitoxantrone dosage was determined to be 8 mg/m(2)/day. Among 19 patients administered the drug at the recommended dosage, 1 patient (5.3%) showed partial response, 8 patients (42.1%) showed stable disease and 10 patients (52.6%) showed progressive disease. The median survival and median progression-free survival were 8.4 and 2.5 months, respectively. The most common toxicities were Grade 3-4 leukopenia (63.2%) and neutropenia (68.4%).
Conclusions: Mitoxantrone at 8 mg/m(2) combined with uracil/tegafur at 300 mg/m(2)/day was determined to be the recommended regimen. Although this regimen was generally well tolerated, it appeared to have little activity against advanced hepatocellular carcinoma. These findings do not support the use of this combination regimen in practice.