High dose mitoxantrone with peripheral blood progenitor cell rescue: Toxicity, pharmacokinetics and implications for dosage and schedule

A. Ballestrero, F. Ferrando, A. Garuti, P. Basta, R. Gonella, M. Esposito, M. O. Vannozzi, G. Sorice, D. Friedman, M. Puglisi, F. Brema, G. S. Mela, M. Sessarego, F. Patrone

Research output: Contribution to journalArticle

Abstract

The optimal use of mitoxantrone (NOV) in the high-dose range requires elucidation of its maximum tolerated dose with peripheral blood progenitor cell (PBPC) support and the time interval needed between drug administration and PBPC reinfusion in order to avoid graft toxicity. The aims of this study were: (1) to verify the feasibility and haematological toxicity of escalating NOV up to 90 mg m-2 with PBPC support; and (2) to verify the safeness of a short (96 h) interval between NOV administration and PBPC reinfusion. Three cohorts of ten patients with breast cancer (BC) or non-Hodgkin's lymphoma (NHL) received escalating doses of NOV, 60, 75 and 90 mg m-2 plus melphalan (L-PAM), 140-180 mg m-2, with PBPC rescue 96 h after NOV. Haematological toxicity was evaluated daily (WHO criteria). NOV plasma pharmacokinetics was also evaluated, as well as NOV cytotoxicity against PBPCs. Haematological recovery was rapid and complete at each NOV dose level without statistically significant differences, and there were no major toxicities. NOV plasma concentrations at the time of PBPC reinfusion were below the toxicity threshold against haemopoietic progenitors. It is concluded that, when adequately supported with PBPCs, NOV can be escalated up to 90 mg m-2 with acceptable haematological toxicity. PBPCs can be safely reinfused as early as 96 h after NOV administration.

Original languageEnglish
Pages (from-to)797-804
Number of pages8
JournalBritish Journal of Cancer
Volume76
Issue number6
Publication statusPublished - 1997

Keywords

  • High-dose chemotherapy
  • Mitoxantrone
  • Peripheral blood progenitor cells

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Fingerprint Dive into the research topics of 'High dose mitoxantrone with peripheral blood progenitor cell rescue: Toxicity, pharmacokinetics and implications for dosage and schedule'. Together they form a unique fingerprint.

  • Cite this

    Ballestrero, A., Ferrando, F., Garuti, A., Basta, P., Gonella, R., Esposito, M., Vannozzi, M. O., Sorice, G., Friedman, D., Puglisi, M., Brema, F., Mela, G. S., Sessarego, M., & Patrone, F. (1997). High dose mitoxantrone with peripheral blood progenitor cell rescue: Toxicity, pharmacokinetics and implications for dosage and schedule. British Journal of Cancer, 76(6), 797-804.