Double-blind placebo-controlled randomized clinical trial evaluating doxycycline effects on chemotherapy-induced oral mucositis.

ABSTRACT

WHAT IS KNOWN AND OBJECTIVE: 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. METHODS: 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. RESULTS AND DISCUSSION: 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 (DG8.1%, PG12.3%; P = .59). The mean OM Assessment Scale score was 2.51, without differences between groups (DG2.7, PG2.4; 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. WHAT IS NEW AND CONCLUSION: Subantimicrobial doses of doxycycline did not reduce the incidence, onset, duration or severity of OM.