Efficacy, Safety and Tolerability of Biotene Mouthwash Versus Aloe Vera Juice and Active Manuka Honey for Prophylaxis of Oral Mucositis Following Chemoradiotheray
Authors: Chang Kian Meng , Ong Tee Chuan , Tan Sen Mui , Tan Swee Kim 
Published: April 2020

Abstract
Background: Oral mucositis (OM) is a common and debilitating complication following high dose Methotrexate (MTX) as well as conditioning regimen for hematopoietic stem cell transplantation (HSCT). The mucosal injury varies in severity, ranging from mild inflammation to full thickness mucosal ulceration extending into submucosal layer. In the setting of damaged mucosal layer and neutropenia, secondary infection may happen which can lead to systemic sepsis. The vicious cycle of inflammation and secondary sepsis will trigger greater release of cytokines, such as tumor necrosis factor alpha and interleukin 1 beta that further worsen the mucosal insult. Patients who develop OM not only suffer from pain and poor quality of life but also infections which can be life-threatening. Obviously, OM causes increased duration of hospital stay, use of parenteral narcotics and nutrition support with increased treatment costs. Currently, there are no definitive approved methods/agents except Palifermin (Keratinocyte growth factor, KGF) that can prevent and/or reduce the severity, incidence and duration of OM. However, the use of Palifermin in our centre is constrained by its cost. Therefore, we explored the feasibility of locally available cheaper agents such as Biotene mouthwash, and the Aloe Vera juice and active Manuka Honey.
Biotene mouthwash is alcohol free and contains antibacterial enzymes that reduce bacterial growth, oral irritation and promote gingival health. Aloe barbodensis inner leaf juice and honey is claimed to contain nutrients, minerals and vitamins.
Patients and Methods: A total of 76 patients were enrolled between September 2007 and February 2008. Application of Biotene mouthwash was done every 6 hourly whereas Aloe Vera juice was consumed twice a day. All HSCT patients received oral Ciprofloxacin, Acyclovir and Fluconazole until Day +21 as prophylaxis. Patients receiving high dose MTX were hyperhydrated with urinary alkalinization. The degree of mucositis was assessed daily by nurses using the WHO grading of mucositis. Physicians were allowed to prescribe intravenous narcotics, analgesics and TPN and ICU care as required. Patients were requested to filll a self reported OM daily questionnaire based on usual analogue scale.
Results: A total of 46 patients received Biotene mouthwash and 30 patients received Aloe Vera juice.
29/46 (63%) vs. 13/30 (43.3%) received high dose MTX in the Biotene arm and Aloe Vera juice arm, respectively, whereas 17/46 (37%) vs. 17/30 (56.7%) received HSCT.
The prevalence of grade 0, 1–2, 3–4 mucositis in patients received Biotene mouth wash and Aloe Vera juice are 17.4%, 52.2%, 30.4% and 26.7%, 56.7%, 16.7% respectively (Chi Square for trend, p = 0.145).
Requirement for intravenous opioid was 0/46(0%) vs. 4/30(13.3), and TPN requirement was 0/46(0%) vs. 2/30(6.7).
None of the patients required ICU management.
Conclusions: Biotene mouthwash is similar to Aloe Vera juice in reducing/preventing the severity of mucositis in patient underwent MTX or conditioning regimen for HSCT. Both are safe and well tolerated. The can be considered as useful local measures in the prophylaxis of OM following chemoradiotheray.