A Review of Clinical Radioprotection and Chemoprotection for Oral Mucositis

Abstract

The first tenet of medicine, "primum non nocere" or "first, do no harm", is not always compatible with oncological interventions e.g., chemotherapy, targeted therapy and radiation, since they commonly result in significant toxicities. One of the more frequent and serious treatment-induced toxicities is mucositis and particularly oral mucositis (OM) described as inflammation, atrophy and breakdown of the mucosa or lining of the oral cavity. The sequelae of oral mucositis (OM), which include pain, odynodysphagia, dysgeusia, decreased oral intake and systemic infection, frequently require treatment delays, interruptions and discontinuations that not only negatively impact quality of life but also tumor control and survivorship. One potential strategy to reduce or prevent the development of mucositis, for which no effective therapies exist only best supportive empirical care measures, is the administration of agents referred to as radioprotectors and/or chemoprotectors, which are intended to differentially protect normal but not malignant tissue from cytotoxicity. This limited-scope review briefly summarizes the incidence, pathogenesis, symptoms and impact on patients of OM as well as the background and mechanisms of four clinical stage radioprotectors/chemoprotectors, amifostine, palifermin, GC4419 and RRx-001, with the proven or theoretical potential to minimize the development of mucositis particularly in the treatment of head and neck cancers.

Figure 1

Neutrophil and Macrophage Polarization During the Early and Late Stages of Mucositis

Figure 2

Flow chart of management Adapted from Napenas

Figure 3

Illustration of the 5 phases of mucositis adapted from Sonis

Figure 4

Amifostine as a thiol-based free radical scavenger, which prevents DNA damage

Figure 5

Redox cycling of the catalytic metal, Mn, in GC4419

Figure 6

Schema of RRx-001-mediated oxidative preconditioning, resulting in potential chemoprotection and radioprotection