Cancer Center, Taipei Veterans General Hospital, Taipei, Taiwan.
Int J Radiat Oncol Biol Phys. 2012 Mar 15;82(4):1463-70. doi: 10.1016/j.ijrobp.2011.04.029. Epub 2011 Aug 11.
Deleterious oral mucositis (OM) develops during radiotherapy (RT) or chemoradiotherapy for head-and-neck cancer (HNC) patients. There are currently no effective cytoprotective treatments for OM without a potential risk of tumor protection. This randomized, double-blind, placebo-controlled pilot study aimed to determine the therapeutic safety and efficacy of phenylbutyrate (an antitumor histone deacetylase inhibitor and chemical chaperone) 5% mouthwash for treating OM caused by cancer therapy.
Between September 2005 and June 2006, 36 HNC patients were randomized to standard oral care plus 5 mL of either phenylbutyrate 5% mouthwash (n = 17) or placebo (mouthwash vehicle, n = 19) taken four times daily (swish and spit). Treatment began when mild mucositis (Radiation Therapy Oncology Group Grade 1) occurred, and ended 4 weeks after RT completion. Safety and efficacy were based on adverse events, physical examination, laboratory determinations, vital signs, Oral Mucosa Assessment Scale (OMAS) and World Health Organization scores, the ability to eat, body weight change, local control, and survival.
We found no severe drug-related side effect. At RT doses of 5500-7500 cGy, phenylbutyrate significantly mitigated the severity of mucositis compared with placebo, based on both the WHO score (severity ≥ 3; p = 0.0262) and the OMAS scale (ulceration score ≥ 2; p = 0.0049). The Kaplan-Meier estimates for 2- and 3-year local control, and overall survival were 100% and 80.8%, and 78.6% and 64.3%, respectively, in the phenylbutyrate group and 74.2% and 74.2%, and 57.4% and 50.2%, respectively, in the placebo group.
This pilot trial suggested that phenylbutyrate mouthwash significantly decreased the impact of OM in HNC patients receiving RT or chemoradiotherapy and did not confront the tumor control. Larger Phase II randomized trials are needed to confirm these results.
头颈部癌症（HNC）患者在接受放疗（RT）或放化疗期间会发生有害的口腔粘膜炎（OM）。目前尚无有效的 OM 细胞保护治疗方法，且这些治疗方法可能会对肿瘤保护产生潜在风险。本随机、双盲、安慰剂对照的初步研究旨在确定 5%苯丁酸钠（一种抗肿瘤组蛋白去乙酰化酶抑制剂和化学伴侣）漱口液治疗癌症治疗引起的 OM 的治疗安全性和疗效。
2005 年 9 月至 2006 年 6 月，36 例 HNC 患者被随机分为标准口腔护理加 5mL 苯丁酸钠 5%漱口液（n=17）或安慰剂（漱口液载体，n=19），每日 4 次（漱口并吐出）。当出现轻度粘膜炎（放射治疗肿瘤学组 1 级）时开始治疗，并在 RT 完成后 4 周结束。安全性和疗效基于不良事件、体格检查、实验室检查、生命体征、口腔粘膜炎评估量表（OMAS）和世界卫生组织评分、进食能力、体重变化、局部控制和生存情况。
我们未发现严重的药物相关副作用。在 RT 剂量为 5500-7500cGy 时，与安慰剂相比，苯丁酸钠显著减轻了粘膜炎的严重程度，这基于 WHO 评分（严重程度≥3；p=0.0262）和 OMAS 量表（溃疡评分≥2；p=0.0049）。苯丁酸钠组 2 年和 3 年的局部控制和总生存率的 Kaplan-Meier 估计值分别为 100%和 80.8%，78.6%和 64.3%，安慰剂组分别为 74.2%和 74.2%，57.4%和 50.2%。
本初步试验表明，苯丁酸钠漱口液可显著降低接受 RT 或放化疗的 HNC 患者 OM 的影响，且不会对肿瘤控制造成影响。需要更大规模的 II 期随机试验来证实这些结果。
