title: A pharmacokinetic evaluation of  topotecan  as a cervical cancer therapy.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors: NYU Langone Medical Center, Department of Obstetrics and Gynecology, NY, USA.
authors: Fernanda
authors: F
authors: Musa
authors: Stephanie
authors: S
authors: Blank
authors: Franco
authors: F
authors: Muggia
mesh_terms: D000818:Animals; D002986:Clinical Trials as Topic / Q000379:methods / Q000639:trends; D004353:Drug Evaluation, Preclinical / Q000379:methods / Q000639:trends; D005260:Female; D006801:Humans; D059004:Topoisomerase I Inhibitors / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019772:Topotecan / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000378:metabolism*
chemical_list: D059004:Topoisomerase I Inhibitors; D019772:Topotecan