Open Access

Periodontal effects of two innovative oral rinsing substances in oncologic patients

  • Authors:
    • Diana Cristala Kappenberg‑Niţescu
    • Ionut Luchian
    • Ioana Mârțu
    • Sorina-Mihaela Solomon
    • Silvia Mârţu
    • Liliana Păsărin
    • Alexandra Mârțu
    • Ioana-Andreea Sioustis
    • Ancuța Goriuc
    • Monica Tatarciuc
  • View Affiliations

  • Published online on: November 26, 2020     https://doi.org/10.3892/etm.2020.9530
  • Article Number: 98
  • Copyright: © Kappenberg‑Niţescu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Chemotherapy often presents side effects, including oral adverse effects that may interfere with the completion of the oncology treatment, threatening the outcome of the treatment and significantly affecting the quality of life of the patient. The aim of the present study was to evaluate two antiseptic, antimicrobial and antifungal substances that may be used in order to achieve improved oral hygiene and to lower the prevalence of side effects during chemotherapy. Patients were randomly divided into three groups: Placebo, oral rinse with cetrimide and mouth coating with a pharmacy‑made compound (nystatin, neomycin and metronidazole). Their oral hygiene and periodontal parameters were determined at baseline and 14 days of use. It was revealed that the most effective clinical results were achieved in the group that used cetrimide mouth rinse that highlighted the best improvements of parameter values, whereas the control and coating‑using group did not obtain statistically significant improvements. Cetrimide oral rinse was demonstrated to be an efficient adjunct method in achieving better oral hygiene and improved periodontal parameters in chemotherapy patients. The present study offers an alternative to the commonly used compounds that may present unwanted side effects in patients during chemotherapy, it promotes the importance of good oral hygiene in the prevention of chemotherapy‑induced oral adverse effects and improves the quality of life of the patient.

Introduction

The side effects of chemotherapy often pose an important problem that both patients and medical personnel are confronted with during treatment. The characteristics of cytotoxic agents manifest both systemically and locally, in various degrees of severity with an incidence of up to 100% of chemotherapy cases (1). It is well known that one of the most severe side effects is myelosuppression and the cascade of events generated by it, such as neutropenia, leucopenia, thrombocytopenia and even pancytopenia (2). The resulted immunosuppression significantly increases the risk of infectious complications that have the potential to interfere with chemotherapy outcome and results and threaten the life of the patient (3).

The primary target of chemotherapy drugs are malignant cells; however, considering the lack of cell specificity, these substances interfere with some of the normal tissues as well. The specific tissues affected by chemotherapy present a high turnover cellular rate in the basal layer, including digestive tract mucosa, bone marrow, hair follicle tissue, respiratory tract mucosa and oral soft tissues. The result within the oral cavity is the appearance of mucositis, infections, dysgeusia, hyposialia or xerostomia, and an increased probability of hemorrhage (4).

The periodontal disease represents a multi-factorial condition affecting the supporting tissues of teeth that, in the absence of treatment, leads to a progressive decrease of attachment, tooth mobility and ultimately, tooth loss (5). The bone destruction that occurs is highly correlated with the level of periodontal inflammation and can also be influenced by the interactions between the periodontal pathogenic bacteria, host immune response as well as other factors including infections, chemotherapy, immune suppression (6).

The aim of the present study was to evaluate the effects of two antiseptic, antimicrobial and antifungal products on oral cavity and periodontal tissues in oncologic patients during chemotherapy.

Patients and methods

The study was conducted on 50 subjects with ages ranging between 48 and 60 years old, between November 2015 and October 2016 at the Oncology Clinic of ‘Victoria’ Hospital in Iaşi, Romania. The present study was approved by the Ethics Committee of ‘Grigore T. Popa’ University of Medicine and Pharmacy (Iasi, Romania). All patients included in the sample population signed an informed consent prior to being accepted to take part in this study. The total number of subjects included in the present study consisted of 22 females and 28 males, thus 44% were women and 56% were men, the distribution being similar regarding the sex (Table I). Most patients were from urban areas (90%) and only a small percentage were from rural areas (10%).

Table I

Subject distribution in groups according to the oral antimicrobial, antiseptic and antifungal substance used.

Table I

Subject distribution in groups according to the oral antimicrobial, antiseptic and antifungal substance used.

SubstanceAbsolute frequencyPercentage frequency
Placebo (control)1224.0
Oral rinse2244.0
Oral coating1632.0
Total50100.0

Most patients were retired and only 20% were still working or unemployed. The chemotherapy administered to the patients was comprised of cisplatin, oxaliplatin and gemcitabine, the highest frequency of antineoplastic drugs being cisplatin (n=26, 52%), followed by oxaliplatin (n=17, 34%) and gemcitabine (n=7, 14%) (Fig. 1).

The patients included in the present study suffered from systemic cancer, were undergoing chemotherapy and had a form of periodontal disease. In order to avoid compromising the relevance and validity of the results, the following exclusion criteria were considered: i) tobacco smokers; ii) patients with infectious and/or inflammatory disease that may have affected the periodontal status, with the exception of systemic cancer; iii) patients that had had periodontal treatment in the previous 6 months; iv) patients that had had antibiotherapy or anti-inflammatory treatment in the previous 3 months, with the exception of chemotherapy; vi) patients that used antiseptic oral rinses or medical toothpaste.

All subjects were randomly split into three groups: i) controls, which included chemotherapy patients that did not use any active substance throughout the present study; ii) group A, which included chemotherapy patients that used oral rinses with cetrimide mouthwash three times a day; iii) group B, that included chemotherapy patients that used mouth coating with a pharmacy-made compound two times a day.

The clinical examination considered several elements: probing depth (PD), clinical attachment loss (CAL), dental mobility (M), plaque index and periodontal disease index (PDI) In addition, pathological probing depths higher than 3 mm on teeth with no gingival recessions were considered. The clinical examination took place at two time-points: T0, before beginning to use the active substances and T1, after 14 days of antiseptic, antimicrobial and antifungal substance usage.

The two substances evaluated in the present study were Citrolin oral rinse and an oral coating recipe developed at the pharmaceutical laboratory BabyFarm, Ltd. Citrolin is an oral rinsing solution that contains 25 mg cetrimide, 3 mg lidocaine and excipients per 100 ml of product and is administered in the form of oral rinses 15 ml per rinse, three times a day. The oral coating substance was developed in collaboration with BabyFarm, Ltd. laboratory and its composition contains neomycin, nystatin, metronidazole, sodium bicarbonate, vitamin A, xylene 2% and oleum helianthi.

The three groups were evaluated based on oral hygiene and periodontal status before the commencement of oral rinse use and oral coating and 14 days after use. None of the patients declared any side effects after using the two compounds included in the present study.

The statistical analysis of the data included in the present study consisted of descriptive statistics, one Sample t-test and a paired Sample t-test using the SPSS software version 21.0 (IBM Corporation). P<0.05 was considered to indicate a statistically significant difference.

Results

The paired Sample t-test revealed a high statistical significance of improvements for group A that used Citrolin oral rinse, the positive modification of all parameters being statistically significant (P<0.05), with the exception of dental mobility, as revealed in Table II.

Table II

Statistical significance analysis for group A, between time-point T0 and T1.

Table II

Statistical significance analysis for group A, between time-point T0 and T1.

 Group A, Citrolin oral rinse T0-T1
Analyzed indicesMean differencetP-value
Silness-Loe Plaque index0.0922.3580.028
PDI0.1042.0970.048
PBI0.1653.5780.002
Mean dental mobility-0.045-1.8210.083
Mean PD0.1454.661<0.001
Mean CAL0.1613.4090.003

[i] Bold indicates statistical significance. PDI, periodontal disease index; PBI, papillary bleeding index; PD, probing depth; CAL, clinical attachment loss.

The results obtained for the controls revealed an increase in the values of all analyzed indices and periodontal disease progression. The modifications of values for these indices had statistical significance with the exception of the average tooth mobility value that had no statistical significance (P=0.077) (Table III). Similarly, group B that used oral coating did not exhibit any improvement of the indices evaluated (data not shown).

Table III

Statistical significance analysis for controls between time-points T0 and T1.

Table III

Statistical significance analysis for controls between time-points T0 and T1.

 Placebo group T0-T1
Quantified indicesMean DifferencetP-value
Silness-Loe Plaque Index-0.164-2.6800.021
PDI-0.472-4.5130.001
PBI-0.301-7.473<0.001
Mean tooth mobility-0.080-1.9480.077
Mean PD-0.479-4.8230.001
Mean CAL-1.183-3.4670.005

[i] Bold indicates statistical significance. PDI, periodontal disease index; PBI, papillary bleeding index; PD, probing depth; CAL, clinical attachment loss.

Moreover, CAL values were different for each of the three chemotherapy agents included in the study between T0 and T1. The average value of CAL was increased in patients treated with oxaliplatin (mean difference=-0.239) and cisplatin (mean difference=-0.19) (data not shown).

Discussion

The efficiency of antineoplastic treatment with platinum-based drugs (cisplatin, oxaliplatin) has been demonstrated multiple times in the past (7,8), although what does sometimes limit their dosage is their potential side effects. Patients treated with one of these chemotherapy agents may develop up to 40 specific adverse reactions. The most important and frequent effect is nephrotoxicity in the case of cisplatin administration and neurotoxicity in the case of oxaliplatin alongside the well-known myelosuppressive effects (1).

Ideally, periodontal disease should be assessed and treated before the beginning of chemotherapy, bearing in mind that a pre-chemotherapy evaluation and maintaining good oral hygiene has been demonstrated to be efficient in preventing oral and systemic complications during anti-neoplasic treatment (9). Frequent erythematous lesions, ulcerations or candidiasis can occur in the oral cavity during chemotherapy (3). Moreover, modifications of periodontal parameters can be observed through an increase in the quantity of oral bacterial plaque, an exacerbation of gingival inflammatory signs and even modifications of the bacterial community composition at oral and periodontal levels (10).

The use of antimicrobial and antiseptic substances is efficient in plaque reduction and improving periodontal parameters (11). Cetrimide, the active substance in Citrolin, is an antiseptic with multiple quaternary ammonium salts that has a bactericidal effect on a wide spectrum of gram-positive and gram-negative bacteria (12). Its action consists of affecting the permeability of the bacterial cellular membrane. It is used in a high number of pharmaceutical compounds with the role to decrease the level of gingival pain and increase oral hygiene (13). It is sometimes used in products that also contain chlorhexidine gluconate (14); however, in the present study, cetrimide was the only active substance in the oral rinse to avoid errors in the results. The use of cetrimide can eliminate bacterial plaque to a great extent, some authors claiming that it has an even higher antimicrobial effect than that of chlorhexidine (15). The effects of cetrimide were also demonstrated to be efficient in preventing carious lesions; a concentration of 0.2% cetrimide used as oral rinse for a minute had the capacity to destroy Streptococcus mutans in a proportion of >99% (16).

Conversely, presently, there are available substances with topic application that contain either only metronidazole, or neomycin and prednisolone (17). In the present study, we selected to introduce a new compound with topical administration that contained neomycin and metronidazole with the aim of evaluating its periodontal efficiency. This combination of drugs has been used in the past, but in association with general surgery of the digestive tract. The pre-operatory administration was revealed to be an efficient combination of antibiotics that leads to a significant reduction of post-operatory infections (18,19).

The most important modifications of the Silness-Loe plaque index were observed in the subjects of group A that used oral rinses with cetrimide. The values of the plaque index were decreased after 14 days of using cetrimide and consequently improved the level of oral hygiene. Conversely, higher values in T1 compared to T0 in the control group (2.002 vs. 1.838) were obtained, thus manifesting an increase of 0.164 between the two evaluations. The values of the plaque index in group B were also increased after 14 days (T1=2.055 vs. T0=1.996) (data not shown).

Another fact for consideration is the medullar modifications that occur during chemotherapy that lead to thrombocytopenia, which can be translated into a pronounced tendency to gingival bleeding in the oral cavity, especially in the conditions of a pre-existing periodontal disease (20). In the study, the PBI exhibited a decrease in value for group A after the 14 days of oral rinsing, signifying an improvement in the periodontal inflammatory status (T1=2.120 vs. T0=2.285; difference =0.165). Then again, controls had higher values of the bleeding index in T1 (T1=2.338 vs. T0=2.037) and group B exhibited similar values at both evaluations (T1=2.206 vs. T0=2.238) (data not shown). These results reflect the modifications obtained for the level of oral hygiene, creating an association between the level of oral hygiene and level of bleeding at the periodontal level.

The average PD obtained in the present study revealed considerable differences between the controls and patients that used antimicrobial/antiseptic/antifungal substances. The highest improvements were observed in group A, which used cetrimide oral rinses. This may be explained by the fact that cetrimide has a higher salivary retention rate than chlorhexidine immediately after the rinse is performed, but decreases more significantly at 4 h than chlorhexidine (21), which is why the patients were recommended to perform the action of rinsing more often than they would otherwise in order to maintain an optimal concentration in the saliva and at the periodontal level.

Oral mucositis and periodontal disease progression are important modifiers for the level of quality of life of patients undergoing chemotherapy and negatively impact the affective state of patients (22), as we have shown in a previous study (23). The present study offers more options regarding the secondary means of oral hygiene that oncology patients can use in order to prevent the progression of periodontal disease and obtain an improved periodontal status during chemotherapy, thus improving their experience during chemotherapy and obtaining an improvement in their level of quality of life (24-26).

It can thus be concluded that cetrimide oral rinses were demonstrated to be the most efficient secondary means of oral hygiene assessed in the present study. Cetrimide oral rinse decreased the level of bacterial plaque and gingival bleeding and it was efficient in preventing the progression of periodontal disease in patients undergoing chemotherapy.

The present results offer new perspectives regarding a reliable alternative to the contemporary-used secondary means of oral hygiene for oncologic patients undergoing chemotherapy. Thus, the periodontal status of these particular patients can be better controlled and their quality of life can be significantly improved.

Acknowledgements

Professional editing, linguistic and technical assistance was performed by Mrs. Irina Radu, Individual Service Provider, certified translator in Medicine and Pharmacy.

Funding

The study was partially funded by the ‘Grigore T. Popa’ University of Medicine and Pharmacy Iași-Romania, during the PhD studies of Dr Diana Cristala Kappenberg-Niţescu.

Availability of data and materials

The data used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Authors' contributions

DCKN, IL, IM, SM and SMS designed the study. AG and MT contributed substantially in drafting the work and revising it critically for important intellectual content. LP, IAS and AM contributed to the data analysis and data interpretation and edited the final form of the manuscript. All authors read and approved the final manuscript.

Ethical approval and consent to participate

The present study was approved by the Ethics Committee of ‘Grigore T. Popa’ University of Medicine and Pharmacy (Iasi, Romania). All protocols were in accordance with the provisions of the Declaration of Helsinki. All patients included in the sample populations signed an informed consent prior to being accepted to take part in this study.

Patient consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

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Spandidos Publications style
Kappenberg‑Niţescu DC, Luchian I, Mârțu I, Solomon S, Mârţu S, Păsărin L, Mârțu A, Sioustis I, Goriuc A, Tatarciuc M, Tatarciuc M, et al: Periodontal effects of two innovative oral rinsing substances in oncologic patients. Exp Ther Med 21: 98, 2021
APA
Kappenberg‑Niţescu, D.C., Luchian, I., Mârțu, I., Solomon, S., Mârţu, S., Păsărin, L. ... Tatarciuc, M. (2021). Periodontal effects of two innovative oral rinsing substances in oncologic patients. Experimental and Therapeutic Medicine, 21, 98. https://doi.org/10.3892/etm.2020.9530
MLA
Kappenberg‑Niţescu, D. C., Luchian, I., Mârțu, I., Solomon, S., Mârţu, S., Păsărin, L., Mârțu, A., Sioustis, I., Goriuc, A., Tatarciuc, M."Periodontal effects of two innovative oral rinsing substances in oncologic patients". Experimental and Therapeutic Medicine 21.1 (2021): 98.
Chicago
Kappenberg‑Niţescu, D. C., Luchian, I., Mârțu, I., Solomon, S., Mârţu, S., Păsărin, L., Mârțu, A., Sioustis, I., Goriuc, A., Tatarciuc, M."Periodontal effects of two innovative oral rinsing substances in oncologic patients". Experimental and Therapeutic Medicine 21, no. 1 (2021): 98. https://doi.org/10.3892/etm.2020.9530