Pilot study of high-dose mitoxantrone and busulfan plus autologous bone transplantation in patients with advanced malignancies

We performed a pilot trial of high-dose mitoxantrone 15 mg/m² by i.v. infusion daily on days -6 to -4 and busulfan 1 mg/kg orally every 6 h (16 doses) on days -7 to -4 plus autologous bone marrow transplantation (BMT) in 10 patients with advanced cancer to determine the safety and feasibility of the combination. The median age of the study group was 42 years, all were women and all had progressed after prior chemotherapy (including doxorubicin in seven cases). Disease types included adenocarcinoma of the breast (n = 6) or ovary (n = 3), and non-Hodgkin's lymphoma (n = 1). The median time to an absolute neutrophil count ≥ 0.5 x 10⁹/L and platelets ≥ 50 x 10⁹/L were 16.5 and 28 days, respectively. There was a high degree of severe regimen-related toxicity, including severe mucositis (n = 7) and veno-occlusive disease (VOD) of the liver (n = 3). Three patients developed multisystem failure and died within 90 days of autologous BMT from complications related to VOD of the liver (n = 2) or septic shock (n = 1). We conclude that the dose and schedule of busulfan and mitoxantrone used in this study was associated with a high degree of unacceptable regimen-related toxicity.