title: Is there a role for  tirapazamine  in the treatment of cervical cancer?
abstract: BACKGROUND
  Cervical cancer is the second-most common malignancy in women worldwide. Cisplatin was introduced as a radiosensitizer in 1999 to improve chances of survival. Tumor cell hypoxia, however, remains a major limiting factor in the treatment of solid tumors with chemotherapy and radiation. There has since been significant interest in the use of bioreductive agents to overcome the hypoxia and improve survival. The addition of tirapazamine (TPZ) to conventional chemoradiation protocols in the management of cervical cancer held promise in the initial Phase I and II clinical trials in delaying recurrence and improving survival. However, GOG recently announced early closure of the Phase III trial of tirapazamine in cervical cancer due to a lack of increased survival.
  
  
  METHODS
  This article covers the definition of hypoxic tumor cells, the markers of tumor hypoxia, methods for measuring hypoxia as well as the pharmacologic action of tirapazamine in hypoxic media. Furthermore, it critically evaluates TPZ's role in cervical cancer treatment and the drawbacks to the GOG study. The authors review all clinical trials published to date with special emphasis on cervical cancer. A systematic review of the literature was also undertaken with PubMed and Ovid.
  
  
  CONCLUSIONS
  Despite the promising results from early clinical trials, it has been shown that the addition of tirapazamine appears to confer no benefits on progression-free or overall survival in patients with cervical cancer. Success in the future will require smaller randomized trials with biologic targets that have acceptable toxicity and efficacy.
authors.affiliation: Tom Baker Cancer Centre, Department of Gynecologic Oncology, Calgary, Alberta, Canada. prafull.ghatage@albertahealthservices.ca
authors.forename: Prafull
authors.initials: P
authors.lastname: Ghatage
authors.forename: Hassan
authors.initials: H
authors.lastname: Sabagh
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D015687:Cell Hypoxia / Q000187:drug effects; D002945:Cisplatin / Q000627:therapeutic use; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005260:Female; D006801:Humans; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*; D055502:Secondary Prevention; D000077704:Tirapazamine; D014227:Triazines / Q000627:therapeutic use*; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy*
chemical_list: D011838:Radiation-Sensitizing Agents; D014227:Triazines; D000077704:Tirapazamine; D002945:Cisplatin