High-dose mitoxantrone with peripheral blood progenitor cell rescue: toxicity, pharmacokinetics and implications for dosage and schedule
Autor: | Fabio Ferrando, M. O. Vannozzi, P. Basta, Alberto Ballestrero, D. Friedman, Fulvio Brema, Franco Patrone, G. Sorice, Anna Garuti, Mario Sessarego, Roberta Gonella, Maria Puglisi, M. Esposito, Giuseppe Sandro Mela |
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Jazyk: | angličtina |
Rok vydání: | 1997 |
Předmět: |
Melphalan
Male Cancer Research medicine.drug_class Cell Survival Antineoplastic Agents Breast Neoplasms Pharmacology Antimetabolite Pharmacokinetics stomatognathic system Antineoplastic Combined Chemotherapy Protocols Medicine Humans Progenitor cell Mitoxantrone Dose-Response Relationship Drug business.industry Lymphoma Non-Hodgkin medicine.disease bacterial infections and mycoses Hematopoietic Stem Cells Lymphoma Hematopoiesis Granulocyte macrophage colony-stimulating factor Oncology Immunology Toxicity Female business medicine.drug Research Article |
Zdroj: | British Journal of Cancer |
ISSN: | 1532-1827 0007-0920 |
Popis: | 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. |
Databáze: | OpenAIRE |
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