Increasing 1-beta-D-arabinofuranosylcytosine efficacy by scheduled dosing intervals based on direct measurements of bone marrow cell kinetics.
Cancer Res
; 54(24): 6446-51, 1994 Dec 15.
Article
em En
| MEDLINE
| ID: mdl-7987841
ABSTRACT
The therapeutic efficacy of cell cycle phase-specific drugs can be improved by repeated administrations, the dosing interval being related to the cell cycle time of the susceptible normal host tissue. Kinetic measurements of bone marrow cell proliferation, with bromodeoxyuridine labeling and flow cytometry analysis, were used to determine the optimal dosing intervals of 1-beta-D-arabinofuranosylcytosine for minimizing bone marrow cell damage in mice. The results showed that cells surviving a single dose 1-beta-D-arabinofuranosylcytosine treatment remained temporarily blocked at the G1-S boundary, and upon release from the block the cells crossed through S phase in a nearly synchronized way. The optimal spacing of repeated treatments, evaluated by measurements of the drug-induced transit times through the different cell cycle phases, equaled the bone marrow cell cycle time following treatment. Repeated 1-beta-D-arabinofuranosylcytosine injections according to this protocol markedly diminished drug toxicity in C3H mice, as compared to protocols of other time intervals. A therapeutic schedule based on these measurements was highly effective in lymphoma-bearing mice the designed protocol of dosing intervals significantly delayed tumor growth whereas other intervals were highly toxic.
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Base de dados:
MEDLINE
Assunto principal:
Medula Óssea
/
Citarabina
Tipo de estudo:
Guideline
Limite:
Animals
Idioma:
En
Revista:
Cancer Res
Ano de publicação:
1994
Tipo de documento:
Article
País de afiliação:
Itália