To determine the safety and efficacy of
mitoxantrone use in hyperbilirubinemic
breast cancer patients, a prospectively determined dosage schedule was evaluated in a multi-center trial. Pretreatment
bilirubin prospectively defined three groups: Controls (with normal
bilirubin) and two Study groups (with either moderate or severe
bilirubin increase).
Bilirubin determined initial
mitoxantrone dose as well:
bilirubin less than 3.5 mg/dl, 14 mg/m2; and
bilirubin greater than or equal to 3.5 mg/dl, 8 mg/m2.
Mitoxantrone at 14 mg/m2 was well tolerated in patients with moderate hepatic dysfunction. Patients with severe hepatic dysfunction demonstrated a mixed toxicity picture, with performance status (ECOG level 3) defining a population with limiting myelosuppression and/or early death. The survival of Study patients with severe hepatic dysfunction (median 17 days) was significantly worse than both Control (p less than 0.01) and Study (p less than 0.05) patients with lower
bilirubin. Entry performance status (ECOG level 0-2 versus level 3) profoundly influenced survival (median survival 222 days versus 25 days, respectively, p less than 0.0001). Objective responses were seen in patients with both normal and elevated
bilirubin.
Bilirubin reduction following
mitoxantrone commonly occurred, representing at least an
indicator of favorable prognosis. Recommendations for
mitoxantrone use include: 1. Patients with moderate
bilirubinemia tolerate 14 mg/m2
mitoxantrone with reasonable chance for benefit. 2. Patients with severe hepatic dysfunction and poor performance status should not be given
mitoxantrone. A definitive recommendation regarding use of reduced 8 mg/m2
mitoxantrone in patients with severe
hyperbilirubinemia and favorable performance status requires further study.