Ramírez-Amador V, Anaya-Saavedra G, Labardini-Méndez J, Ponce de León-Rosales S
Oral Pathology and Oral Medicine Master, Universidad Autonoma Metropolitana, Mexico City, Mexico.
Hemato-Oncology Department, Instituto Nacional de Cancerología, Mexico City, Mexico.
J Clin Pharm Ther. 2018 Apr;43(2):202-208. doi: 10.1111/jcpt.12633. Epub 2017 Sep 25.
Chemotherapy (CT)-associated oral mucositis (OM) is one of the most debilitating and painful side effects in oncology patients, with limited effective management options. During CT, matrix metalloproteinases (MMPs) are upregulated, causing damage in mucosal and submucosal tissues, and playing a key role in OM; therefore, the use of subantimicrobial doxycycline as a MMP inhibitor may represent a potential approach for OM management. The aim of this clinical trial was to evaluate the efficacy and safety of low doses of doxycycline in OM development in individuals with acute leukaemia (AL) during CT.
Randomized controlled clinical trial (Registration No. NCT01087476) performed in adult AL patients scheduled to receive CT (September 2010-October 2014). Individuals were stratified by leukaemia type and assigned randomly to receive doxycycline hyclate (50 mg/d) (doxycycline group: DG) or placebo (placebo group: PG) before and during CT. Included subjects had a baseline oral examination and thereafter 3 times a week during 21 days. The primary outcome was OM development.
One hundred and forty-seven AL subjects were enrolled: 74 in DG and 73 in PG; baseline characteristics between groups were comparable. During follow-up, 15 (10.2%) individuals developed OM; no differences between treatment groups were found (DG:8.1%, PG:12.3%; P = .59). The mean OM Assessment Scale score was 2.51, without differences between groups (DG:2.7, PG:2.4; P = .65). Low baseline blood albumin levels in the OM-affected individuals were identified, revealing the effect of systemic deterioration as a predisposing factor for OM development. No adverse effects were observed.
Subantimicrobial doses of doxycycline did not reduce the incidence, onset, duration or severity of OM.
化疗（CT）相关的口腔黏膜炎（OM）是肿瘤患者中最使人虚弱且疼痛的副作用之一，有效的治疗选择有限。在化疗期间，基质金属蛋白酶（MMPs）上调，导致黏膜和黏膜下组织受损，在口腔黏膜炎中起关键作用；因此，使用亚抑菌剂量的强力霉素作为MMP抑制剂可能是一种治疗口腔黏膜炎的潜在方法。本临床试验的目的是评估低剂量强力霉素对急性白血病（AL）患者化疗期间口腔黏膜炎发生的疗效和安全性。
对计划接受化疗的成年急性白血病患者进行随机对照临床试验（注册号：NCT01087476）（2010年9月至2014年10月）。患者按白血病类型分层，随机分配在化疗前及化疗期间接受盐酸强力霉素（50mg/d）（强力霉素组：DG）或安慰剂（安慰剂组：PG）。纳入的受试者进行了基线口腔检查，此后在21天内每周检查3次。主要观察指标是口腔黏膜炎的发生情况。
共纳入147例急性白血病受试者：强力霉素组74例，安慰剂组73例；两组间基线特征具有可比性。随访期间，15例（10.2%）患者发生口腔黏膜炎；治疗组之间未发现差异（强力霉素组：8.1%，安慰剂组：12.3%；P = 0.59）。口腔黏膜炎评估量表的平均得分是2.51，组间无差异（强力霉素组：2.7，安慰剂组：2.4；P = 0.65）。确定了口腔黏膜炎患者的低基线血白蛋白水平，揭示了全身状况恶化作为口腔黏膜炎发生的易感因素的作用。未观察到不良反应。
亚抑菌剂量的强力霉素并未降低口腔黏膜炎的发生率、发病时间、持续时间或严重程度。
