Table 2.
Overview of hypoxia targeting strategies investigated in HNSCC.
| Hypoxia- Targeting Strategy | HNSCC Trials | Treatment Schedule | Hypoxia Detection Method | Outcome | Toxicity |
|---|---|---|---|---|---|
| HBO | Overview by Overgaard [95] | RT with HBO or RT alone | / | Improved local control (p = 0.003) | Increased normal tissue toxicity |
| TPZ | RTOG 98.0 (phase II) [96,97] | Chemo-RT with TPZ or chemo-boost | 18F-MISO PET | Hypoxic tumors improved locoregional control (p = 0.015) | More febrile neutropenia and grade 3 or 4 late mucous membrane toxicity |
| ARCON | Janssens et al. (phase III) [98] | ARCON or accelerated RT alone | Pimonidazole (exogeneous marker) | Hypoxic tumors improved regional control (p = 0.04) | Similar (however lower RT dose in ARCON arm |
| Nimorazole | DAHANCA 5 (phase III) [38] | RT with nimorazole or placebo | 15-gene hypoxia classifier | HPV-negative hypoxic tumors improved locoregional control (p = 0.002) | Minor nausea and vomiting |
| PR-104 | Preclinical data [99,100,101] | / | / | Selective activation and enhanced antitumor effects | Dose-limiting myelotoxicity |
| CP-506 | Preclinical data [102] | / | / | Favorable pharmacokinetics and broad antitumor activity | / |
RT: Radiotherapy, HBO: Hyperbaric oxygenation, TPZ: Tirapazamine.