Administration of a phorbol ester to patients with hematological malignancies: preliminary results from a phase I clinical trial of 12-O-tetradecanoylphorbol-13-acetate.
Clin Cancer Res
; 8(8): 2512-8, 2002 Aug.
Article
em En
| MEDLINE
| ID: mdl-12171877
ABSTRACT
PURPOSE:
Phorbol esters are capable of inducing a broad range of cellular effects,including the maturation/differentiation of hematopoietic cell lines (E. Huberman and M. F. Callaham, Proc. Natl. Acad. Sci. USA, 76 1293-1297, 1979; J. Lotem and L. Sachs, Proc. Natl. Acad. Sci. USA, 76 5158-5162, 1979; G. Rovera et al., Proc. Natl. Acad. Sci. USA, 76 2779-2783, 1979; H. P. Koeffler, J. Clin. Investig., 66 1101-1108, 1980). The ability to induce this differentiation at very low concentrations stimulated investigators to administer a phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA), to patients with myeloid leukemias in the People's Republic of China (Z. T. Han et al., Proc. Natl. Acad. Sci. USA, 95 5357-5361, 1998). The tolerability of this therapy in China prompted Phase I studies of TPA in the United States. The purpose of this report is to demonstrate the tolerance of TPA at doses that result in detectable biological activity in blood and malignant cells. EXPERIMENTALDESIGN:
TPA was administered to patients with relapsed/refractory hematological malignancies.RESULTS:
Phenotypic effects were detected in malignant cells and TPA-associated biological activity was present in blood for up to several hours after the infusion.CONCLUSIONS:
These studies confirm the feasibility of TPA administration to humans and establish the foundation for the development of phorbol esters as therapy for patients with a variety of malignant and nonmalignant disorders.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Acetato de Tetradecanoilforbol
/
Neoplasias Hematológicas
Limite:
Adult
/
Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Clin Cancer Res
Ano de publicação:
2002
Tipo de documento:
Article