Mitoxantrone as Combination Chemotherapy in Patients with Acute Leukemia

Abstract

A phase III study of mitoxantrone (MIT) in acute leukemia was conducted by the Tokai Blood Cancer Study Group between February, 1983 and April, 1985.
The study involved 53 patients with adequate renal and hepatic function and aging under 70 years old.
Twenty seven patients with acute nonlymphocytic leukemia (ANLL) and four patients with myeloid crisis of chronic myelogenous leukemia (CML) were treated with MIT in combination with behenoyl cytosine arabinoside, 6-MP and prednisolone (BHAC-MMP). As to ANLL, 7 of 8 patients in first induction, 3 of 4 in primarily refractory, 8 of 11 in relapse and 2 of 4 in relapse and refractory achieved complete remission (CR), respectively. Two of four patients with myeloid crisis of CML achieved CR. The disease free survival rate of CR cases with ANLL achieved at the first induction was 42% at 70 weeks after initiation of treatment and that at the reinduction was 28%, respectively. Twenty patients with acute lymphocytic leukemia (ALL) and two patients with lymphoid crisis of CML were treated with MIT in combination with vincristine sulfate and prednisolone (MVP). As to ALL, 8 of 8 patients in first induction, 3 of 4 in primarily refractory, 4 of 5 in relapse and 1 of 3 in relapse and refractory achieved CR, respectively. None of 2 patients with lymphoid crisis of CML achieved CR. The disease free survival rate of CR cases with ALL achieved at the first induction was 38% at 40 weeks after initiation of treatment and that at the reinduction was 13%, respectively.
The present regimen, however, results in a more prolonged duration of leukopenia than that of thrombocytopenia. So, infectious complications happened rather frequently such as sepsis in 23% with BHAC-MMP regimen and 18% with MVP regimen. Side effects included anorexia, alopecia, nausea and vomiting, hepatic dysfunction and stomatitis, but no significant cardiac toxicity occurred in this study.
These studies suggest that MIT in combination with other drugs is of high value in the treatment of patients with acute leukemia.