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Expert Opin Drug Metab Toxicol ; 9(2): 215-24, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23320990

RESUMO

INTRODUCTION: Topotecan was initially approved for the treatment of recurrent ovarian cancer. In cervical cancer, it has been investigated for its potential as part of systemic therapy for advanced and/or recurrent disease and in combination with cisplatin and radiation as a first-line treatment for advanced disease. As a topoisomerase I (topo I) inhibitor, its activity is predicted to be schedule-dependent and potentiated in a schedule-dependent manner by its interaction with DNA damaging agents. AREAS COVERED: The cytotoxicity of topotecan is believed to be due to double-stranded DNA damage produced when the DNA replication 'fork' on the opposing DNA strand is interrupted by the ternary complex formed by topotecan, topoisomerase I and DNA. This review focuses on: i) combination studies of cisplatin + topotecan both as neoadjuvant and with concomitant radiation; ii) adding this drug as a radiosensitizer in pilot studies for locally advanced disease and iii) topotecan as part of non-cisplatin combinations in metastatic disease. EXPERT OPINION: Cervical cancer continues to claim many victims among parts of the world where early detection and/or vaccination programs are not systemically applied. Topotecan is an attractive building block for improving therapy against advanced disease.


Assuntos
Inibidores da Topoisomerase I/farmacocinética , Topotecan/farmacocinética , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/metabolismo , Animais , Ensaios Clínicos como Assunto/métodos , Ensaios Clínicos como Assunto/tendências , Avaliação Pré-Clínica de Medicamentos/métodos , Avaliação Pré-Clínica de Medicamentos/tendências , Feminino , Humanos , Inibidores da Topoisomerase I/uso terapêutico , Topotecan/uso terapêutico
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