Hypoxia in head and neck cancer: studies with hypoxic positron emission tomography imaging and hypoxic cytotoxins.

نویسندگان

  • Danny Rischin
  • Richard Fisher
  • Lester Peters
  • June Corry
  • Rodney Hicks
چکیده

The importance of hypoxia as a potential obstacle to the successful treatment of head and neck squamous cell carcinoma (HNSCC) has been recognized for a long time. The presence of hypoxia as detected by oxygen electrodes has been shown to be an adverse prognostic factor in head and neck cancer treated with radiotherapy (RT) (1). Progress has been hampered by the difficulties in measuring hypoxia in patients with HNSCC enrolled in clinical trials and by the limited efficacy observed with interventions designed to overcome hypoxia in HNSCC. Treatment approaches to overcome hypoxia have included the use of hypoxic cell sensitizers, hyperbaric oxygen, high linear energy transfer radiation, and accelerated RT with carbogen and nicotinamide. A conceptually different approach is the incorporation of bioreductive agents, such as the benzotriazine compound, tirapazamine (3-amino-1,2,4benzotriazine 1,4-dioxide) (TPZ). TPZ is a hypoxic cell cytotoxin, rather than a hypoxic cell sensitizer, which maintains its differential toxicity relative to aerobic cells over a wide range of low oxygen concentrations (2). In the 1990s, the focus of TPZ development was on testing this drug in combination with platinum-based chemotherapy, predominantly for metastatic non–small-cell lung cancer. Several small studies have combined TPZ with RT, although often for diseases for which the efficacy of RT is limited and the importance of hypoxia as a mechanism limiting efficacy has not been established. One previous trial of TPZ and RT in HNSCC has been published (3). Because the evidence of the importance of hypoxia in limiting efficacy in localregionally advanced HNSCC treated with RT is strong,

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عنوان ژورنال:
  • International journal of radiation oncology, biology, physics

دوره 69 2 Suppl  شماره 

صفحات  -

تاریخ انتشار 2007