Document Detail

Is there a role for tirapazamine in the treatment of cervical cancer?
MedLine Citation:
PMID:  23033890     Owner:  NLM     Status:  MEDLINE    
INTRODUCTION: 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.
AREAS COVERED: 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.
EXPERT OPINION: 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.
Prafull Ghatage; Hassan Sabagh
Publication Detail:
Type:  Journal Article; Review     Date:  2012-10-04
Journal Detail:
Title:  Expert opinion on drug metabolism & toxicology     Volume:  8     ISSN:  1744-7607     ISO Abbreviation:  Expert Opin Drug Metab Toxicol     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-11-16     Completed Date:  2013-04-25     Revised Date:  2013-11-06    
Medline Journal Info:
Nlm Unique ID:  101228422     Medline TA:  Expert Opin Drug Metab Toxicol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1589-97     Citation Subset:  IM    
Tom Baker Cancer Centre, Department of Gynecologic Oncology, Calgary, Alberta, Canada.
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MeSH Terms
Antineoplastic Combined Chemotherapy Protocols / therapeutic use
Cell Hypoxia / drug effects
Cisplatin / therapeutic use
Clinical Trials, Phase I as Topic
Clinical Trials, Phase II as Topic
Disease Models, Animal
Drug Evaluation, Preclinical
Radiation-Sensitizing Agents / therapeutic use*
Recurrence / prevention & control
Triazines / therapeutic use*
Uterine Cervical Neoplasms / drug therapy*
Reg. No./Substance:
0/Radiation-Sensitizing Agents; 0/Triazines; 15663-27-1/Cisplatin; 27314-97-2/tirapazamine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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