口腔黏膜炎的治疗主要是缓解症状,首要目标是减轻疼痛。在后续化疗和/或放疗期间,应实施有效的预防措施,以降低疾病的再发率并减轻症状。下列治疗推荐和建议大部分来源于癌症支持治疗多国协会和国际口腔肿瘤协会 (Multinational Association of Supportive Care in Cancer and the International Society of Oral Oncology, MASCC/ISOO) 发布的循证指南。[9]Lalla RV, Bowen J, Barasch A, et al. MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy. Cancer. 2014;120:1453-1461.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4164022/http://www.ncbi.nlm.nih.gov/pubmed/24615748?tool=bestpractice.com
口腔护理
所有患者应进行口腔护理。[15]McGuire DB, Fulton JS, Park J, et al. Systematic review of basic oral care for the management of oral mucositis in cancer patients. Support Care Cancer. 2013;21:3165-3177.http://www.ncbi.nlm.nih.gov/pubmed/24018908?tool=bestpractice.com包括保持良好的口腔卫生,如使用软毛牙刷刷牙、使用牙线,以及避免口腔组织的损伤。对牙体表面进行专业的灌洗和清创并对口腔黏膜进行无创性的清洁可能是合适的。每日多次使用漱口水(半茶匙小苏打粉溶于一杯温水中)漱口能改善口腔湿润度。也可考虑使用其他漱口液,例如羧乙基纤维素溶液。
疼痛控制
对于轻度至中度黏膜炎患者,仅仅口服止痛药(例如对乙酰氨基酚或布洛芬)并局部使用利多卡因凝胶或含漱液即足以控制疼痛。其他能够减轻疼痛的局部药物包括吗啡漱口水或多虑平漱口水。这些药物需要药剂师来配制。[25]Saunders DP, Epstein JB, Elad S, et al. Systematic review of antimicrobials, mucosal coating agents, anesthetics, and analgesics for the management of oral mucositis in cancer patients. Support Care Cancer. 2013;21:3191-3207.http://www.ncbi.nlm.nih.gov/pubmed/23832272?tool=bestpractice.com[26]Leenstra JL, Miller RC, Qin R, et al. Doxepin rinse versus placebo in the treatment of acute oral mucositis pain in patients receiving head and neck radiotherapy with or without chemotherapy: a phase III, randomized, double-blind trial (NCCTG-N09C6 [Alliance]). J Clin Oncol. 2014;32:1571-1577.http://www.ncbi.nlm.nih.gov/pubmed/24733799?tool=bestpractice.com
对于严重溃疡性黏膜炎,通常需要全身应用阿片类镇痛剂来充分控制疼痛。这类药物包括曲马多、羟考酮或吗啡。对于接受传统剂量或高剂量化疗的患者,芬太尼透皮贴剂可以用于口腔黏膜炎的治疗。对于正在进行造血干细胞移植的患者,推荐使用吗啡进行患者自控镇痛,可以减少每小时阿片类药物的用量,同时缩短疼痛持续时间。[25]Saunders DP, Epstein JB, Elad S, et al. Systematic review of antimicrobials, mucosal coating agents, anesthetics, and analgesics for the management of oral mucositis in cancer patients. Support Care Cancer. 2013;21:3191-3207.http://www.ncbi.nlm.nih.gov/pubmed/23832272?tool=bestpractice.com
恶性肿瘤治疗期间的预防措施:
对于正在接受造血干细胞移植、高剂量黏膜毒性药物如氟尿嘧啶、以及接受口腔放疗的患者,应实施有效预防措施。
对于正在接受骨髓毒性治疗、需要造血支持的血液系统恶性肿瘤患者,重组人角质细胞生长因子- 1(帕利夫明)可减少严重口腔黏膜炎的发生率和持续时间。[11]Spielberger R, Stiff P, Bensinger W, et al. Palifermin for oral mucositis after intensive therapy for hematologic cancers. N Engl J Med. 2004;351:2590-2598.http://www.nejm.org/doi/full/10.1056/NEJMoa040125#t=articlehttp://www.ncbi.nlm.nih.gov/pubmed/15602019?tool=bestpractice.com在化疗之前和之后3天连续3天给药。对于接受自体干细胞移植,进行高剂量化疗和全身放疗的血液系统恶性肿瘤患者,建议使用帕利夫明。[27]Raber-Durlacher JE, von Bültzingslöwen I, Logan RM, et al. Systematic review of cytokines and growth factors for the management of oral mucositis in cancer patients. Support Care Cancer. 2013;21:343-355.http://www.ncbi.nlm.nih.gov/pubmed/2298709?tool=bestpractice.com接受同种异体移植的患者可以考虑使用这种药物。[16]Hensley ML, Hagerty KL, Kewalramani T, et al. American Society of Clinical Oncology 2008 clinical practice guideline update: use of chemotherapy and radiation therapy protectants. J Clin Oncol. 2009;27:127-145.http://jco.ascopubs.org/cgi/content/full/27/1/127http://www.ncbi.nlm.nih.gov/pubmed/19018081?tool=bestpractice.com对于在未使用全身放疗、非干细胞移植的情况下或者实体瘤治疗时的用药,目前尚无充足的数据。[16]Hensley ML, Hagerty KL, Kewalramani T, et al. American Society of Clinical Oncology 2008 clinical practice guideline update: use of chemotherapy and radiation therapy protectants. J Clin Oncol. 2009;27:127-145.http://jco.ascopubs.org/cgi/content/full/27/1/127http://www.ncbi.nlm.nih.gov/pubmed/19018081?tool=bestpractice.com
对于接受高剂量美法仑(作为血液系统恶性肿瘤清髓治疗方案的一部分)的患者,以及静脉推注氟尿嘧啶的患者,推荐在化疗药物输注前、输注期间及输注后口含冰块或冰水,以预防口腔黏膜炎的发生。[10]Peterson DE, Ohrn K, Bowen J, et al. Systematic review of oral cryotherapy for management of oral mucositis caused by cancer therapy. Support Care Cancer. 2013;21:327-332.http://www.ncbi.nlm.nih.gov/pubmed/22993025?tool=bestpractice.com[28]Riley P, Glenny AM, Worthington HV, et al. Interventions for preventing oral mucositis in patients with cancer receiving treatment: oral cryotherapy. Cochrane Database Syst Rev. 2015;(12):CD011552.http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD011552.pub2/fullhttp://www.ncbi.nlm.nih.gov/pubmed/26695736?tool=bestpractice.com [
]Can oral cryotherapy help to prevent chemotherapy-induced oral mucositis?http://cochraneclinicalanswers.com/doi/10.1002/cca.1255/full显示答案
对于有金属牙修复体的患者,可用牙齿保护套、棉卷、或石蜡等使黏膜和金属隔离,从而防止射线接触金属后发生反向散射,引起相邻部位的黏膜炎。[16]Hensley ML, Hagerty KL, Kewalramani T, et al. American Society of Clinical Oncology 2008 clinical practice guideline update: use of chemotherapy and radiation therapy protectants. J Clin Oncol. 2009;27:127-145.http://jco.ascopubs.org/cgi/content/full/27/1/127http://www.ncbi.nlm.nih.gov/pubmed/19018081?tool=bestpractice.com
在造血干细胞移植前,接受高剂量化疗或放化疗的患者,以及接受头颈部放疗而未接受化疗的患者,弱激光疗法可减轻口腔黏膜炎的严重程度。[17]Migliorati C, Hewson I, Lalla RV, et al. Systematic review of laser and other light therapy for the management of oral mucositis in cancer patients. Support Care Cancer. 2013;21:333-341.http://www.ncbi.nlm.nih.gov/pubmed/23001179?tool=bestpractice.com其作用机制尚不明确,但可能是通过促进愈合和抗炎来发挥作用。[18]Lopes NN, Plapler H, Chavantes MC, et al. Cyclooxygenase-2 and vascular endothelial growth factor expression in 5-fluorouracil-induced oral mucositis in hamsters: evaluation of two low-intensity laser protocols. Support Care Cancer. 2009;17:1409-1415.http://www.ncbi.nlm.nih.gov/pubmed/19234862?tool=bestpractice.com[19]Lopes NN, Plapler H, Lalla RV, et al. Effects of low-level laser therapy on collagen expression and neutrophil infiltrate in 5-fluorouracil-induced oral mucositis in hamsters. Lasers Surg Med. 2010;42:546-552.http://www.ncbi.nlm.nih.gov/pubmed/20662031?tool=bestpractice.com很多肿瘤中心不具备弱激光治疗的条件。