Table 1.

Clinical trials performed to overcome hypoxic radioresistance in HNSCC.

Modification	Response	References
Hyperbaric oxygen	Many studies have utilised hyperbaric oxygen administer to HNSCC patients prior to radiotherapy. Safety implications have hindered its progression.	[65,66,67,68,69,70,71]
Carbogen	Carbogen breathing (95% oxygen and 5% carbon dioxide) prior to radiotherapy did not improve local or regional control of HNSCC patient tumours.	[72]
ARCON	Accelerated radiotherapy with carbogen and nicotinamide (ARCON) trials in HNSCC patients generally improved regional tumour control but no benefit on local control.	[73,74]
Nitroimidazoles	Misonidazole and Etanidazole—no differences in tumour control when combined with radiotherapy. Severe side effects were also reported. Nimorazole—increased tumour control when combined with radiotherapy in HNSCC patients but only those with confirmed tumour hypoxia benefitted.	[75,76,77,78,79,80,81]
Tirapazamine	Phase II clinical trials showed promising results for HNSCC patients. However, the success was not sustained into phase III.	[82,83]