Tirapazamine: a novel agent targeting hypoxic tumor cells.
BACKGROUND
Tumor hypoxia remains one of the greatest challenges in the treatment of solid tumors, as cancer cells in these regions are resistant to killing by radiation therapy and most anticancer drugs. Tirapazamine (TPZ) is a newer class of cytotoxic drugs with selective toxicity towards hypoxic mammalian cells.


OBJECTIVE
This article reviews the mechanism of action, toxicity and antitumor activity of the drug and provides insights into factors that may have contributed to the disappointing results in some of the Phase III trials. It also identifies the need to explore dependable markers of tumor hypoxia and limit future trials of this agent to patients who have significant populations of hypoxic tumor cells.


METHODS
We reviewed all clinical trials published to date and present a summary of the results. There are also several ongoing studies, the results of which are pending and may yet impact the clinical use of the drug.


CONCLUSIONS
Despite the very promising results obtained in various preclinical studies and early-Phase clinical trials, several Phase III trials have failed to demonstrate any survival benefit of adding TPZ to chemotherapy or radiation therapy in non-small cell lung cancer or head and neck cancer. Several clinical trials have yet to be completed and reported.
Reddy
Srini B
SB
University of Kansas Medical Center, Division of Hematology/Oncology, 2330 Shawnee Mission Parkway, Suite 210, Westwood, KS 66205, USA.
Williamson
Stephen K
SK
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use*; D015687:Cell Hypoxia / Q000187:drug effects; D002986:Clinical Trials as Topic; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D000077704:Tirapazamine; D016896:Treatment Outcome; D014227:Triazines / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D014227:Triazines; D000077704:Tirapazamine