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.

Dual benefit of supplementary oral 5‐aminolevulinic acid to pelvic radiotherapy in a syngenic prostate cancer model

“…Studies over the past several decades have investigated the pathophysiological and molecular mechanisms underlying RT's effects on tumors and normal tissue. [5][6][7] Although several pharmacological approaches that prevent and mitigate radiation injury in normal tissues have been examined in preclinical studies, only a few have progressed to clinical use. 5 5-aminolevulinic acid (ALA) is widely used to induce protoporphyrin IX (PPIX), a photosensitizer used in photodynamic diagnosis and therapy for non-muscle invasive bladder cancer.…”

“…Recent technical advances in the field of RT planning and delivery enable the administration of higher radiation doses with equal or less toxicity. Studies over the past several decades have investigated the pathophysiological and molecular mechanisms underlying RT's effects on tumors and normal tissue . Although several pharmacological approaches that prevent and mitigate radiation injury in normal tissues have been examined in preclinical studies, only a few have progressed to clinical use …”

The effects of radiotherapy and chemotherapy on oral tissues

“…Lokalna sekundarna oralna infekcija, kao posledica mijelosupresije najčešća je komplikacija hemoterapije i može dovesti do sepse i smrtnog ishoda 10 . Druge komplikacije vezane za hemoterapiju su: disbalans elektrolita, hemoragija, akutna intoksikacija lekovima (uključujući povraćanje i mučninu), fotosenzitivnost, disfunkcija centralnog nervnog sistema, alopecija i malnutricija.…”

“…Chemotherapy, for the malignant head and neck lesions, can cause alteration of the oral cavity mucosa. Local secondary oral infection, as a consequence of myelosuppression, is the most frequent complication of chemotherapy, and could lead to the septic shock and death 10 . Other chemotherapy side effects are: electrolyte imbalance, hemorrhage, acute drug intoxication (including vomiting and nausea), photosensitivity, central nervous system dysfunction, alopetion and malnutrition.…”

The relationship between TNF-α gene promoter polymorphism (− 1211 T > C), the plasma concentration of TNF-α, and risk of oral mucositis and shortening of overall survival in patients subjected to intensity-modulated radiation therapy due to head and neck cancer

“…Grade 3-severe, painful ulcers extending to more than half of the oral mucosa, do not allow oral intake but liquids intake are preserved. Grade 4-painful ulcers covering almost all mucosal surfaces, any alimentation by oral is impossible [3,5,6]. Serve OM (3rd-4th degree) can be found in nearly 1/3 of patients with HNC [4,7].…”