Oronsky Bryan, Goyal Sharad, Kim Michelle M, Cabrales Pedro, Lybeck Michelle, Caroen Scott, Oronsky Neil, Burbano Erica, Carter Corey, Oronsky Arnold
EpicentRx Inc, 4445 Eastgate Mall, Suite 200, San Diego, CA 92121, USA.
The George Washington University, Department of Radiation Oncology, 22nd & I Street, NW DC Level, Washington, DC 20037.
Transl Oncol. 2018 Jun;11(3):771-778. doi: 10.1016/j.tranon.2018.03.014. Epub 2018 Apr 23.
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.
医学的首要原则“首要,勿伤”,即“首先,不要造成伤害”,并不总是与肿瘤学干预措施(如化疗、靶向治疗和放疗)兼容,因为这些干预措施通常会导致明显的毒性。更常见且严重的治疗引起的毒性之一是粘膜炎,尤其是口腔粘膜炎(OM),其被描述为口腔黏膜或内衬的炎症、萎缩和破损。口腔粘膜炎(OM)的后遗症包括疼痛、吞咽痛、味觉障碍、口腔摄入量减少和全身感染,这些后遗症常常需要延迟治疗、中断治疗和停止治疗,这不仅会对生活质量产生负面影响,还会对肿瘤控制和生存产生不利影响。减少或预防粘膜炎发生的一种潜在策略是给予被称为辐射防护剂和/或化学防护剂的药物,目前尚无有效的治疗方法,只有最佳的支持性经验护理措施,这些药物旨在有区别地保护正常组织而非恶性组织免受细胞毒性作用。这篇范围有限的综述简要总结了口腔粘膜炎的发病率、发病机制、症状及其对患者的影响,以及四种临床阶段辐射防护剂/化学防护剂(氨磷汀、帕利夫明、GC4419和RRx-001)的背景和作用机制,这些药物已被证实或理论上有潜力将粘膜炎的发生降至最低,尤其是在头颈部癌症的治疗中。