Toxicity antagonists in head and neck cancer.

Clinical trials of altered fractionation and concurrent chemoradiation regimens have better elucidated the limits of both acute and late normal tissue toxicities in the head and neck. Acute effects on mucosal epithelium represent the principal barrier to intensification of radiation or chemoradiation schedules. Late soft tissue injury and organ dysfunction limit efforts to escalate radiation total dose. New insights into the cellular and molecular mechanisms of injury repair allow new strategies in the management and prevention of treatment-related toxicity. Toxicity antagonists are agents that directly interfere with the mechanism of toxicity or modulate the normal tissue response to injury. This article reviews 10 agents under development. Not only could such interventions reduce treatment-related morbidity, but they may also allow treatment intensification in advanced disease.