Sucralfate is an ulcer drug that has an anti-inflammatory effect on the gastrointestinal mucosa. The drug causes an increase in the level of prostaglandins and binds basic fibroblast growth factor (bFGF), protecting it from acid degradation. It is angiogenic, increasing blood flow. Systemic use with oral administration has been studied for diarrhea, mucositis, and radiodermatitis. Topical use has been tested as an intervention for radiodermatitis.
Kwong, K.K. (2004). Prevention and treatment of oropharyngeal mucositis following cancer therapy: Are there new approaches? Cancer Nursing, 27(3), 183–205.
Database searched was MEDLINE (1993–2003) for randomized, controlled trials evaluating mucositis interventions.
A total of 50 randomized controlled trials were presented. Other trials and papers were referenced.
The author concluded that most agents require more study.
The author noted the problem of variation in study protocols, insufficient sample sizes, and a lack of consensus regarding the scoring system for mucositis.
The author noted the need to include psychotherapeutic interventions and management and pointed out the lack of a quality-of-life tool for mucositis.
Qutob, A.F., Gue, S., Revesz, T., Logan, R.M., & Keefe, D. (2013). Prevention of oral mucositis in children receiving cancer therapy: A systematic review and evidence-based analysis. Oral Oncology, 49, 102–107.
To investigate, critically appraise, and rate the evidence regarding agents used for the prevention of mucositis in children
Databases searched included CINAHL, Cochrane library, Ovid MEDLINE, PubMed, BioMed Central, and other internet-based sources. A total of 19 databases were searched.
Search keywords were mucositis, stomatitis, oral inflammation, mouth mucosal inflammation, prophylaxis, management, and prevent; in addition to keywords to identify children and all types of cancer therapy.
Studies were included in the search if they
Studies were excluded if they
The authors concluded that oral care protocols should be used; oral sucralfate suspension, prostaglandin E2, and GM-CSF mouthwash should not be considered based on current evidence; and chlorhexidine (without use as part of an oral care protocol), laser therapy, and glutamine should not be considered because of conflicting evidence.
Findings provide further support for use of oral care protocols. Results provided no other useful recommendations for preventive therapies but identified the need for further research in this area.
Saunders, D.P., Epstein, J.B., Elad, S., Allemano, J., Bossi, P., van de Wetering, M.D., . . . Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO). (2013). Systematic review of antimicrobials, mucosal coating agents, anesthetics, and analgesics for the management of oral mucositis in cancer patients. Supportive Care in Cancer, 21, 3191—3207.
STUDY PURPOSE: To develop clinical practice guidelines on the use of antimicrobials, mucosal coating agents, anesthetics, and analgesics for the prevention and management of oral mucositis
TYPE OF STUDY: Systematic review
DATABASES USED: Ovid, MEDLINE
KEYWORDS: Acyclovir, amitriptyline, adhesive, amphotericin B, analgesic, analgesia, antacid, antibiotic, anti-infective, alfentanil, aqua oral, benzocaine, coating agent, clarithromycin, diclosan, doxepin, fentanyl, film, fluconazole, gabapentin, IB-367, hydromorphone, iseganan, kaopectate, ketamine, kefir, lidocaine, local anesthetic, “magic” or “miracle” mouthwash, mouth rinse or mouthwash, mucoadhesive, methadone, morphine, nystatin, patient controlled, polymyxin, povidone-iodine, polyvinylpyrrolidone, protegrin, sucralfate, tetracaine, tetracycline, tobramycin, topical, zilactin, xylocaine. In addition, the brand names of commercial products in these categories also were searched, including Gelclair®, MuGard®, and UlcerEase.
INCLUSION CRITERIA: Studies that focused on the use of antimicrobials, coating agents, anesthetics, and analgesics; English studies; published in MEDLINE on or before December 31, 2010; all age groups; and published in a peer-reviewed journal
EXCLUSION CRITERIA: Articles that did not report on effects of an intervention on mucositis, animal or in vitro studies, literature reviews, non-English papers
TOTAL REFERENCES RETRIEVED: 1,384
EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Only articles that reported on the effects of an antimicrobial, mucosal coating agent, anesthetic, or analgesic on oral mucositis that met the inclusion criteria described were included in the review. Also, articles did not have any major or minor flaws per Hadorn and levels of evidence were based on the Somerfield criteria. The results were sorted into three classifications: recommendation, suggestion, and no guidelines possible.
FINAL NUMBER STUDIES INCLUDED = 62
SAMPLE RANGE ACROSS STUDIES, TOTAL PATIENTS INCLUDED IN REVIEW: Not discussed in the review
KEY SAMPLE CHARACTERISTICS: Included patients actively being treated for head and neck cancers, hematologic cancers, and solid tumors with radiotherapy, chemotherapy, chemoradiotherapy, and high-dose total body irradiation for hematopoietic stem cell transplant
PHASE OF CARE: Active treatment
Recommendations were made against the use of topical antimicrobial agents for the prevention of mucositis, including recommendations against the use of iseganan for mucositis prevention in hematopoietic stem cell transplantation (HSCT) and head and neck radiation therapy (RT) and antimicrobial lozenges for mucositis prevention in head and neck RT. Recommendations were made against the use of sucralfate for the prevention and treatment of oral mucositis due to chemotherapy or RT. Recommendations were made for the use of patient-controlled analgesia with morphine in HSCT, transdermal fentanyl in HSCT and standard-dose chemotherapy treatment, and morphine and doxepin mouth rinse in patients with head and neck cancer undergoing RT. No guidelines were recommended for any of the other agents reviewed due to insufficient or conflicting evidence.
Additional well-designed RCT studies are needed on the prevention and management of oral mucositis. Studies that look at systemic dosing and absorption may be helpful.
Lack of high-level of evidence prevented the development of guidelines in many of the agents reviewed, such as topical anesthetics, antimicrobial agents, and mucosal coating agents.
The recommendations for use in clinical practice were made for the use of patient-controlled analgesia with morphine in patients undergoing HSCT and for transdermal fentanyl in HSCT and standard-dose chemotherapy treatment, and morphine and doxepin mouth rinse in patients with head and neck cancer undergoing RT. Any use of the other agents in this study were not recommended for use in the prevention or treatment of oral mucositis and should be used with caution.
Ala, S., Saeedi, M., Janbabai, G., Ganji, R., Azhdari, E., & Shiva, A. (2016). Efficacy of sucralfate mouth wash in prevention of 5-fluorouracil induced oral mucositis: A prospective, randomized, double-blind, controlled trial. Nutrition and Cancer, 68, 456–463.
To determine the efficacy of sucralfate mouthwash in the prevention of oral mucositis (OM) in patients receiving fluorouracil (5-FU) chemotherapy
Patients 18 years and older receiving chemotherapy containing 5-FU and calcium folinate were randomized into two groups through a computer-generated list of random numbers. One group received sucralfate suspension mouthwash and the other group received a placebo. Both groups received 10 ml of either sucralfate or placebo mouthwash every six hours for 10 days after the last dose of chemotherapy. Patients were instructed to rinse their mouth with the suspension for at least five minutes and spit it out 30 minutes after meals to ensure prolonged exposure of the mouthwash to the mucosal membranes.
A statistically significant difference in the severity of mucositis was shown between the sucrafate group and placebo group on both day 5 and day 10 (p = 0.005, p < 0.001), respectively. The severity of mucositis in the sucrafate group on day 5 and 10 was grade 0. The majority of patients in the placebo group had a mucositis severity grade 2 on day 5 and day 10. A statistically significant reduction in pain intensity was shown in the sucrafate group versus the placebo group on both day 5 and day 10 (p = 0.004, p = 0.001), respectively.
Sucralfate mouthwash may be more effective than placebo in the prophylaxis of 5-FU–induced OM. A correlation between both the reduction of pain intensity and mucositis severity was shown with the use of the sucralfate mouthwash suspension, further confirming the role of sucralfate in the prophylaxis of OM in patients receiving 5-FU chemotherapy.
Sucralfate mouthwash may be effective in reducing the severity and pain intensity of OM in patients receiving 5-FU.
Castagna, L., Benhamou, E., Pedraza, E., Luboinski, M., Forni, M., Brandes, I., … Dietrich, P.-Y. (2001). Prevention of mucositis in bone marrow transplantation: A double blind randomised controlled trial of sucralfate. Annals of Oncology, 12, 953–955.
To compare placebo to sucralfate for prevention of mucositis in high-dose chemotherapy and bone marrow transplant (BMT)
Treatment was started one day before the regimen. Patients received one 2 g dose pack every three hours during the day and once during the night if awakened for a maximum of 7 per 24 hours until bone marrow (BM) recovery or end of mucositis.
The study reported on 102 patients hospitalized for allogeneic or autologous BMT.
The study was conducted between April 1991 and November 1993.
This was a prospective, randomized, double-blind study.
Patients were examined twice weekly by two physicians only, recorded prospectively, according to adapted Oral and Maxillofacial Surgeon (OMS) criteria for grafted patients.
Dodd, M.J., Miaskowski, C., Greenspan, D., MacPhail, L., Shih, A., Shiba, G., … Paul, S.M. (2003). Radiation-induced mucositis: A randomized clinical trial of micronized sucralfate versus salt and soda mouthwashes. Cancer Investigation, 21, 21–33.
Patients with head and neck cancer receiving radiation therapy (RT) were instructed to use the PRO_SELF Mouth Aware (PSMA) Program, an oral hygiene protocol, throughout RT. Those who developed RT-induced oral mucositis (OM) were randomized to either 1 gm carafate or normal saline (NS) mouthwash. Patients were instructed to rinse with the mouthwash four times per day. Nurses who were trained in the intervention, PSMA, and oral assessment phoned the patients twice weekly until one month after RT. One month after RT completion, oral assessment was done.
The study reported on 30 adult patients with head and neck cancer receiving RT with or without chemotherapy. The mean age of the sample was 55.2 years.
This was a randomized, double-blind, clinical trial.
The MacDibbs Mouth Assessment was used to measure the severity of OM. Patients also recorded pain when swallowing. Healing, weight loss, tube feeds, breaks in RT, hospital admissions, and Karnofsky Performance Status Scale scores were recorded. The investigators used t-tests and chi-square analysis.
No significant differences were found in the two groups in terms of average worst severity rating (p = 0.85), severe pain (p = 0.54), MacDibbs scores at the end of RT (p = 0.61), average pain at the end of RT (p = 0.51), MacDibbs scores at the follow-up visit (p = 0.24), pain at the follow-up visit (p = 0.41), or days to heal (p = 0.19).
No significant differences were found for any of the other variables as well (e.g., weight loss, tube feeds, breaks in RT).
Etiz, D., Erkal, H.S., Serin, M., Kucuk, B., Hepari, A., Elhan, A.H., … Cakmak, A. (2000). Clinical and histopathological evaluation of sucralfate in prevention of oral mucositis induced by radiation therapy in patients with head and neck malignancies. Oral Oncology, 36, 116–120.
Patient were randomized to receive sucralfate or placebo, delivered in an oral suspension with identical appearance, taste, and consistency. Patients received six 1-gram doses daily at regular intervals beginning on day one of radiation therapy (RT) and throughout RT, including weekends.
The study was conducted between December 1996 and December 1997.
This was a prospective, randomized, double-blind, placebo-controlled trial.
Sucralfate is low in cost, is easily administered, and had a similar compliance rate.
Nottage, M., McLachlan, S.A., Brittain, M.A., Oza, A., Hedley, D., Feld, R., … Moore, M.J. (2003). Sucralfate mouthwash for prevention and treatment of 5-fluorouracil-induced mucositis: A randomized, placebo-controlled trial. Supportive Care in Cancer, 11(1), 41–47.
To evaluate the effectiveness of sucralfate mouthwash in preventing 5-fluorouacil (5-FU) -induced oral mucositis (OM)
Patients were block randomized to receive sucralfate or an identical-appearing placebo. They were instructed to swish 10 ml of mouthwash for 2 minutes and then swallow it. The mouthwash was to be used four times per day starting on day 1 of radiation therapy (RT) and continuing until day 15.
Patients received throat swabs at the beginning of treatment to exclude infection. All patients used cryotherapy and the same salvage treatment (xylocaine topical, acetaminophen/codeine, then morphine sulfate if needed).
Patients were given 1 liter of study drug, and compliance was assessed by the volume left over after day 15. Research nurses contacted each patient by telephone after one week to assess compliance with the mouthwash and complete questionnaires.
This was a randomized, double-blind, placebo-controlled trial.
Patients graded the severity of mucositis at the same time each day (in the evening) for 15 days using a 0–4 rating scale developed by the North Central Cancer Treatment Group. In addition, 1–6 analgesic diaries, the McGill Pain Questionnaire, and a 0–10 quality of life measurement tool were used on follow-up visits.
No significant differences were found between the two groups in terms of the following measures.
More women experienced mucositis than men.
The patient and medical assessments differed, and the authors stated that patient reporting is believed to be more sensitive.
The study did not conclude that sucralfate was an effective solution for the prevention of oral mucositis in this study population.