RESUMO
The optimal design for initial clinical trials of chemopreventive agents for cancer has not been determined. A single design is unlikely to be the model for chemoprevention of cancer, even for prevention of a single subtype of cancer, because of the heterogeneity of drugs under investigation and the variety of biologic effects being targeted. Factors that are important in designing initial clinical trials include the proposed mechanisms of drug action, the ability and types of assays available to detect that activity or pharmacodynamic effect, and the extent of prior clinical experience. In this article, we present a discussion of the factors to be considered in initial activity studies, followed by a specific example of early clinical assessment of a noncytotoxic agent (R-flurbiprofen, E-7869) as a potential chemopreventive agent for prostate cancer.
Assuntos
Anticarcinógenos/farmacologia , Ensaios Clínicos como Assunto/métodos , Flurbiprofeno/uso terapêutico , Neoplasias da Próstata/prevenção & controle , Anticarcinógenos/uso terapêutico , Ensaios Clínicos Fase I como Assunto , Ensaios Clínicos Fase II como Assunto , Interações Medicamentosas , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Humanos , Masculino , Projetos de PesquisaAssuntos
Formação de Anticorpos/efeitos dos fármacos , Imunidade Celular/efeitos dos fármacos , Animais , Anti-Inflamatórios/farmacologia , Azatioprina/farmacologia , Ciclofosfamida/farmacologia , Ciclosporinas/farmacologia , Humanos , Células Híbridas , Imunoglobulinas/imunologia , Inflamação/imunologia , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/imunologia , Leucotrieno B4/farmacologia , Levamisol/farmacologia , Mastócitos/imunologia , Modelos Biológicos , Prostaglandinas/farmacologia , SRS-A/farmacologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologiaRESUMO
Sequential treatment of the protected beta-D-arabinofuran[1',2':4,5]-2-aminooxazoline (2) with methyl isocyanate and diimidazole carbonyl afforded the 2,2'-anhydro-beta-D-arabinofuranosyl nucleoside, 6. Deprotection and hydrolysis yielded the corresponding arabinoside. Although the anhydronucleoside exhibited in vitro antiviral activity against herpes simplex type 1, it exacerbated the infection in vivo. Further examination uncovered an in vitro inhibition of the induction of a cell-mediated immune response without cytotoxicity.