Bethanechol is a cholinergic agent that stimulates the parasympathetic nervous system. It is most often used related to its effect on improvement of bladder emptying and improvement in esophageal gastric sphincter pressure for reflux control. It is also a salivary stimulant. Bethanechol mouth rinse has been evaluated in patients with cancer in the prevention and management of mucositis.
Effectiveness Not Established
Jensen, S.B., Jarvis, V., Zadik, Y., Barasch, A., Ariyawardana, A., Hovan, A., . . . Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO). (2013). Systematic review of miscellaneous agents for the management of oral mucositis in cancer patients. Supportive Care in Cancer, 21(11), 3223–3232.doi: 10.1007/s00520-013-1884-6
To analyze the available literature and define clinical practice guidelines for the use of the following agents for the prevention and treatment of oral mucositis (OM): allopurinol, midline mucosa-sparing radiation blocks, payayor, pentoxifylline, timing of radiation therapy (morning versus afternoon), pilocarpine, bethanechol, chewing gum, propantheline, and tetrachlorodecaoxide
- DATABASES USED: MEDLINE
- KEYWORDS: Oral mucositis, cancer therapy, supportive, palliative, prevention, treatment, and saliva
- Inclusion and exclusion criteria were not listed in this report, but, rather, were referenced from the criteria listed in another referenced study.
A total of 99 references were retrieved. Of these, 18 were excluded based on the inclusion/exclusion criteria (which was not stated in the article). Of the remaining 81 papers, 49 pertained to agents of natural origin and the results on those agents were reported separately. This manuscript reported the results of the review of the remaining 32 papers that tested interventions that did not fit in any of the other categories and were classified as miscellaneous agents.
Studies were evaluated based on the list of major and minor flaws published by Hadorn. Level of evidence was assigned for each intervention based on the Somerfield criteria. A well-designed study was defined as a study with no major flaws per the Hadorn criteria. Findings from the reviewed studies were integrated into guidelines based on the overall level of evidence for each intervention.
- A final sample of 32 papers addressing 10 interventions were included in the report.
- The numbers of patients and sample ranges across all studies were not reported.
- Patient populations included patients receiving high-dose chemotherapy before stem cell transplantation, patients receiving radiation therapy (RT) for head and neck cancer, and patients receiving bone marrow transplantation.
Phase of Care and Clinical Applications:
PHASE OF CARE: Active treatment
Suggestions were made against the use of systemic pilocarpine administered orally for prevention of OM during RT in patients with head and neck cancer and in patients receiving high-dose chemotherapy with or without total body irradiation, prior to hematopoietic stem cell transplantation as well as against the use of systemic pentoxifylline administered orally for the prevention of OM in patients undergoing bone marrow transplantation. No guideline was possible for any other agent reviewed because of inadequate or conflicting evidence.
None of the agents reviewed was determined to be effective for the prevention or treatment of OM. This review was inadequate and difficult for the reader to understand. The methods section was missing needed information to assess the interventions and the associated recommendations.
- The scope of the analysis was too large, as 32 studies were included from which the review panel attempted to make recommendations about 10 different interventions.
- The level of evidence was not explained to the reader, making it difficult to assess the results obtained and impossible to know if the study selection was biased.
- The authors stated that the criteria for a well-designed study was no major flaws per the Hadorn criteria but did not tell the reader what the criteria were.
- The authors were not clear if only well-designed studies were used exclusively.
Many products on the market claim to prevent or treat OM. Nurses need to be well informed before recommending any products or interventions to patients. Further research is needed.
Research Evidence Summaries
Jham, B.C., Chen, H., Carvalho, A.L., & Freire, A.R. (2009). A randomized phase III prospective trial of bethanechol to prevent mucositis, candidiasis, and taste loss in patients with head and neck cancer undergoing radiotherapy: A secondary analysis. Journal of Oral Science, 51, 565–572.doi: 10.2334/josnusd.51.565
To determine the impact of bethanechol administration concomitant to radiotherapy on oral mucositis, candidiasis, and taste loss
Intervention Characteristics/Basic Study Process:
Patients were randomly assigned to one of two treatment groups. Group 1 received 25 mg oral bethanechol, 3 times a day; group 2 received artificial saliva (OralBalance). Patients who experienced severe mucositis were subject to daily laser applications until remission of the lesions.
- The mean age of participants in the bethanechol group was 59 years and in the artificial saliva group was 55 years.
- The sample was 25% female and 75% male in both groups.
- Patients had been diagnosed with malignant neoplasms of the head and neck region and were receiving external beam radiotherapy (RT) encompassing one or more major salivary glands for a minimum of 45 Gy.
This was an outpatient radiation study conducted in Brazil.
Secondary analysis, stratified, open-label, random allocation to one of two groups.
- Mucositis was scored weekly using the World Health Organization (WHO) grading scale.
- Patients were examined weekly for Candida.
- Taste loss was defined as the patient’s subjective report of absence of taste.
- Fisher exact tests were used for categorical variables.
- t-tests were used for continuous variables.
- The Kaplan-Meier method was used.
- Log-rank tests were performed.
No significant differences in frequency and severity of mucositis, candidiasis, or taste loss were found.
Bethanechol did not appear to reduce the incidence of mucositis, candidiasis, or taste loss when administered during RT.
- The sample size was small
- Differences in the anticancer treatment regimen existed between the two groups.
- A wide variety of treatment protocols were used (bethanechol, sucralfate, and laser therapy).
- No delineation was provided as to the type of chemotherapy that patients received. Possible implications exist (e.g., perhaps taste was a factor of chemotherapy).
Larger, randomized, double-blind, placebo-controlled studies are needed possibly to further test the hypothesis that bethanechol could minimize RT-induced mucositis incidence or severity.