Mitoxantrone in elderly patients with advanced breast cancer: Pharmacokinetics, marrow and peripheral hematopoietic progenitor cells

The aims of this study were to evaluate the pharmacokinetics, tolerability and hematopoietic toxicity of mitoxantrone in elderly women. Thirteen patients with advanced breast cancer, median age of 73 years, received escalating doses of mitoxantrone 8, 10, 12 and 14 mg/m 2 on day 1, q 21. There was a linear relationship between the mitoxantrone dose administered and the mitoxantrone exposure (AUC) in plasma (r=0.856, pc0.001). After 4 courses of treatment, a significant decrease in bone marrow cellularity (p=0.0067), and HPC content (BFU-E p=0.0077) was observed. A remarkable, though not statistically significant decrease in circulating HPCs was observed after 4 courses and was still present 8-12 months after the termination of treatment. Therapy with mitoxantrone in elderly women was well tolerated at the dose of 12 mg/m 2 for four courses. The significant hematological toxicity observed in marrow cellularity and HPC content warrant further studies.