The variable number of studies indicates the level of difficulty, complexity, great demand for time, and need for knowledge, among other factors, that are necessary for the successful design of studies.
In the studies analyzed, propolis and benzydamine hydrochloride mouthwashes were effective in reducing OM and OPM, while allopurinol mouthwash with did not show significant results. It is important to note that each patient is unique and may respond differently to treatment. Thus, further studies are needed to develop definitive protocols for the management of OM and OPM in cancer patients.
Allopurinol is a drug commonly used to treat gout, a condition characterized by painful episodes of inflammation in different joints as a result of excess uric acid in the body [21, 53, 54]. The drug acts by inhibiting xanthine oxidase, an enzyme that plays a crucial role in the production of uric acid, causing a decrease in uric acid levels in blood and the consequent relief of pain and inflammation [55].
Allopurinol was evaluated in four articles; three of these studies analyzed patients undergoing chemotherapy and one study evaluated patients undergoing radiotherapy. The randomized, double-blind, placebo-controlled clinical trial 41 investigating patients submitted to radiotherapy found no differences in the severity of OM between the group treated with allopurinol and the control group over the first 2 weeks of treatment. However, there were significant differences between groups from weeks 3 to 6, with significant improvement of mucositis in the allopurinol group. In contrast, the other studies involving patients submitted to chemotherapy found no significant difference between the group that used allopurinol and the other compounds analyzed [21, 53].
Benzydamine is a local analgesic and anti-inflammatory agent that is used to treat a variety of painful and inflammatory conditions, particularly those affecting the mouth and throat. The mechanism of action of benzydamine consists of the inhibition of prostaglandin synthesis, contributing to the reduction in pain and swelling (anti-inflammatory and analgesic) [54, 56].
Three studies evaluated the activity of benzydamine, two including patients undergoing chemotherapy and one including patients undergoing radiotherapy. Only one study [50] found benzydamine hydrochloride to be superior in the prevention and treatment of OM in patients undergoing chemotherapy.
Chlorhexidine is a potent antiseptic agent that acts against a broad spectrum of bacteria, both gram-positive and gram-negative. The compound is often incorporated in oral health products because of its effectiveness in reducing plaque formation and in treating gingivitis [57]. Due to its bactericidal and bacteriostatic activity, chlorhexidine is frequently used in hospital environments for skin disinfection before surgical procedures [58, 59].
Chlorhexidine is the most widely used and recommended mouthwash for patients undergoing cancer treatment because of its bactericidal, fungicidal, and virucidal properties. Six studies analyzed chlorhexidine; of these, one study investigated patients undergoing radiotherapy, one study examined patients undergoing chemotherapy and radiotherapy, and four studies investigated patients undergoing chemotherapy. However, chlorhexidine was not superior in any of these studies when compared to other compounds [60, 61, 62]. It is important to note that one study [46] comparing the efficacy of sodium bicarbonate solution and chlorhexidine in the oral care of patients during induction chemotherapy found the former to be more effective than chlorhexidine mouthwash, reinforcing that the indication of mouthwashes must be well assessed by the patient’s care team.
Propolis is a resin collected by bees from different plants to protect the hive. This resin has antimicrobial, anti-inflammatory, antioxidant, and anticarcinogenic properties; it is therefore a product with different therapeutic applications [63, 64, 65]. The history of propolis use extends into traditional medicine, where it is used to boost immunity and to treat different infections and inflammatory conditions.
Only one study evaluated the effectiveness of propolis [48] and found that it reduced chemotherapy-induced OM. The results showed that the use of propolis as a mouthwash was effective in reducing OM and in improving the oral health of patients.
The methods used in the studies varied widely in terms of study design, active ingredients in the mouthwashes, and substances used for comparison. It is important to note that most studies observed a reduction in OM in patients with different types of cancer despite the wide variety of chemotherapy drugs and doses administered. In some studies, the authors included patients with diverse diseases that required different antineoplastic treatments, a fact that may interfere with the development and severity of OM and OPM (Table 5).
Table 5
Efficacy of medications in the studies analyzed
| Benzydamine (3 articles) | |
Chemotherapy (2) | Chitapanarux et al. [50] Ahmed [47] | Showed efficacy |
Radiotherapy (1) | Gupta et al. [49] | Showed efficacy – no severe mucositis |
| Propolis (1 article) | |
Chemotherapy (1) | Akhaven-Karbassi et al. [48] | Showed efficacy |
| Chlorhexidine (5 articles) | |
Chemotherapy (3) | Afrasiabifar et al. [51] Mehdipour et al. [45] Choi and Kim [46] | Did not show efficacy |
Radiotherapy (1) | Madan et al. [42] Santaella et al. [52] | Did not show efficacy |
Chemotherapy and radiotherapy (1) | Gupta et al. [49] | Did not show efficacy |
| Allopurinol (4 articles) | |
Chemotherapy (3) | Loprinzi et al. [40] Shabanloei et al. [43] Panahi et al. [44] | Did not show efficacy |
Radiotherapy (1) | Abassi-Nazari et al. [41] | Efficacy after 3 weeks |
Source: The authors (2024) |
Benzydamine was shown to be superior to sodium bicarbonate in preventing chemo/radiotherapy-induced OM [50]. On the other hand, sodium bicarbonate mouthwash was more effective than chlorhexidine in the oral care of patients with acute leukemia during induction chemotherapy [46].
The diversity of interventions explored reflects the complexity of mucositis and highlights the importance of multifaceted approaches to the treatment and prevention of OM in cancer patients. Regarding the results obtained, most studies provided qualitative data on the improvement of OM with the use of mouthwashes. However, the lack of standardization impairs the direct comparison of studies and the determination of the relative efficacy of mouthwashes. It is noteworthy that the studies evaluated did not identify important adverse effects of the interventions implemented for the prevention or treatment of OM and OPM.
Regarding limitations, all studies provided incomplete information, including a lack of details about randomization, possible conflicts of interest, and a clear description of the study design. These limitations can affect the interpretation of the results and the risk of bias in the studies. There is also the possibility that studies reporting negative results, especially small ones, have not been published.
The studies provided valuable information on different strategies to prevent and treat OM in cancer patients and thus contribute to the development of more effective approaches using the substances described that can improve the quality of life of patients undergoing antineoplastic treatment. These substances are easily accessible at public or private hospitals and do not require the recruitment of additional technical staff for their use.
Limitations must be considered when interpreting and comparing the results of the studies. Further studies with a robust design that provide more detailed information about the results are needed to obtain stronger scientific evidence.