Oral mucositis and selective elimination of oral flora in head and neck cancer patients receiving radiotherapy: a double-blind randomised clinical trial

Abstract

Mucositis is an acute inflammation of the oral mucosa because of radiotherapy and/or chemotherapy. All patients receiving radiotherapy in the head and neck region develop oral mucositis. The aim of this study was to analyse the effects of selective oral flora elimination on radiotherapy-induced oral mucositis, in a double-blind, randomised, placebo-controlled trial. Sixty-five patients with a malignant tumour in the head and neck regions to be treated with primary curative or postoperative radiotherapy participated in this study. The patients received either the active lozenges of 1 g containing polymyxin E 2 mg, tobramycin 1.8 mg and amphotericin B 10 mg (PTA) (33 patients) or the placebo lozenges (32 patients), four times daily during the full course of radiotherapy. Mucositis, changes in the oral flora, quality of feeding and changes of total body weight were assessed. Mucositis score did not differ between the groups during the first 5 weeks of radiotherapy. Nasogastric tube feeding was needed in six patients (19%) of the placebo group and two patients (6%) of the PTA group (P ¼ 0.08). Mean weight loss after 5 weeks of radiation was less in the PTA group (1.3 kg) (s.d.: 3.0) than in the placebo group (2.8 kg) (s.d.: 2.9) (P ¼ 0.05). Colonisation index of Candida species and Gram-negative bacilli was reduced in the PTA group and not in the placebo group (Po0.05). No effect on other microorganisms was detected. In conclusion, selective oral flora elimination in head and neck irradiation patients does not prevent the development of severe mucositis.

Systematic review of antimicrobials, mucosal coating agents, anesthetics, and analgesics for the management of oral mucositis in cancer patients

“…Amphotericin B is a polyene antifungal, often used intravenously for systemic fungal infections. Although initial pilot studies suggested the potential efficacy of this combination, subsequent larger well-controlled studies clearly demonstrated that topical use of PTA did not prevent OM or reduce its severity [76,77,79,83]. In addition, a well-controlled, multicenter, double-blind RCT examined the effect of a lozenge containing bacitracin, clotrimazole, and gentamicin (BCoG) for the prevention of radiation-induced OM in 137 H&N cancer patients.…”

Host-Microbiome Cross-talk in Oral Mucositis

“…However, given its richness and diversity and its role in local inflammatory diseases, the potential of oral microflora to affect the course of mucositis seemed likely. Adding to this thinking was the finding over 50 y ago of shifts in the oral flora in response to chemotherapy (Peterson et al 1987;Reynolds et al 1989;Peterson 1990;Spijkervet et al 1991;Ruescher et al 1998;Stokman et al 2003;Napenas et al 2010;de Mendonca et al 2012;Laheij et al 2012). Consequently, numerous antimicrobial strategies have been studied as interventions for mucositis.…”

“…Consequently, numerous antimicrobial strategies have been studied as interventions for mucositis. Some have included the administration of systemic antibiotics (selective decontamination), whereas others have tested topical antibacterial therapies (Wijers et al 2001;Stokman et al 2003;Giles et al 2004). None have been successful.…”

Treatment of radiation-induced mucocutaneous toxicity

“…Non-randomised trials reported about 30 to 40% reduction in stomatitis for patients, who followed a daily preventive protocol with chlorhexidine (0.2%) [19]. In a randomised clinical trial [23] preventive antimicrobial medication did not reduce the incidence of mucositis and is not recommended in the prophylactic setting.…”

“…Furthermore in these cells activation of transcription factors such as NF kappa B leads to the up-regulation of genes that modulate apoptosis processes. Direct and indirect epithelial stem cell deaths result in a loss of repopulation capacity and support mucosal surface damage [23,24].…”