Benzydamine for Radiation-Related Mucositis

Benzydamine for Radiation-Related Mucositis

PEP Topic 
Mucositis
Description 

Benzydamine is a nonsteroidal anti-inflammatory drug that has been used in an oral rinse. It has some local anesthetic and analgesic properties. Benzydamine has been evaluated in patients with cancer for the prevention and management of mucositis.

Likely to Be Effective

Research Evidence Summaries

Epstein, J.B., Silverman, S., Paggiarino, D.A., Crockett, S., Schubert, M.M., Senzer, N.N., … Leveque, F.G. (2001). Benzydamine HCl for prophylaxis of radiation-induced oral mucositis: Results from a multicenter, randomized, double-blind, placebo-controlled clinical trial. Cancer, 92, 875–885.

doi: 10.1002/1097-0142(20010815)92:4<875::AID-CNCR1396>3.0.CO;2-1
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Intervention Characteristics/Basic Study Process:

Participants were randomized to receive either benzydamine HCl oral rinse, containing 0.15% benzydamine oral rinse (1.5 mg/ml benzydamine) or placebo, which identical in appearance and taste consisting of the vehicle only (approximately 10% alcohol by volume, menthol, peppermint oil, clove oil, and other flavoring agents).

Patients were to rinse with 15 ml of solution for two minutes, 4–8 times daily, before and during radiation therapy (RT) and for two weeks after completion of RT. If burning or stinging occurred, dilution of the rinse with water at 1:1 or 1:2 was allowed.  

Patients were evaluated before RT, twice weekly during RT, at the end of RT, and 2–3 weeks after RT.

Sample Characteristics:

  • The sample consisted of 172 patients, with 84 receiving benzydamine and 88 receiving placebo.
  • Patients ranged in age from 18–80 years old.
  • Patients had been diagnosed with head and neck cancer and were scheduled to receive at least 5000 cGy RT via megavoltage treatment. Patients were eligible if at least two oral sites were included in RT.
  • Patients were excluded if they had Karnofsky performance status of less than 80%, known hypersensitivity to benzydamine or typical nonsterioidal anti-inflammatory drugs, had residual oral or pharyngeal mucositis from previous RT or chemotherapy, or were already on RT and had taken experimental drugs within 30 days of study start.

Setting:

The study was conducted at 16 centers in North America (15 in the United States and 1 in Canada).

Measurement Instruments/Methods:

  • Mucositis assessment involved evaluating 14 anatomic areas for erythema, pseudomembrane, and ulceration using a 4-point scale ranging from 0–3.
  • Pain in the mouth or throat and pain during meals was assessed on a 7-point categorical self-rating scale ranging from 0–6.

Results:

Benzydamine produced a 26.3% reduction in mean mucositis area under the curve (AUC) compared with placebo for overall 0–5000 cGy (p = 0.009).

Pain also decreased as evidenced by a delay in use of concomitant systemic analgesics. Mouth pain showed a 25.8% reduction in AUC (p = 0.064) versus placebo, and throat pain showed a 22.5% reduction in AUC (p = 0.064).

Pain during meals was not effectively reduced.

Conclusions:

Benzydamine was not effective in reducing more severe mucositis in patients receiving high, single, daily RT regimens of 220 cGy per day or more.

Limitations:

  • The study is limited because of the small sample size.
  • The intervention is not approved by the U.S. Food and Drug Administration.
  • The decrease in pain was not statistically significant.

Hadjieva, T., Cavallin-Stahl, E., Linden, M., & Tiberg, F. (2014). Treatment of oral mucositis pain following radiation therapy for head-and-neck cancer using a bioadhesive barrier-forming lipid solution. Supportive Care in Cancer, 22, 1557–1562. 

doi: 10.1007/s00520-014-2117-3
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Study Purpose:

To test the analgesic effect of CAM2028 with benzydamine compared with CAM2028 without benzydamine (the FDA-approved prescription formula of episil) over an eight-hour period. During treatment with CAM2028, phospholipid and triglceride lipid components self-assemble with a volume of water (saliva) to form a bioadhesive and protective liquid crystalline lining of the oral mucosa. Additional objective of the study was to assess the safety and tolerability of a single-dose of the combined formulation.

Intervention Characteristics/Basic Study Process:

  1. All patients were receiving radical or postoperative radiotherapy to a significant part of clinically visible oral and/or pharyngeal mucosa at two or more anatomic sites.
  2. Trial began during weeks 3 to 4 of radiotherapy and took place over a maximum duration of 12 days.
  3. Treatment randomly was assigned after a radiotherapy treatment period of seven days.
  4. Patients must have received at least one third of the planned total dosage of radiation.
  5. At screening, participants were required to exhibit symptomatic oral mucositis (WHO grade 2 or above). 
  6. Likert score of at least 6 was required at screening and before each treatment.
  7. Patients were treated with randomized study medication on treatment days 1 and 3 and returned for a final follow-up evaluation on day 5.
  8. At the first treatment visit, each patient was randomly allocated to one of two sequences: CAM2028-benzydamine on day 1 followed by CAM20208-control on day 3 or CAM2028-control followed by CAM2028-benzydamine.
  9. Patients were assigned a random number and received trial medication sent from the study coordinating center with the corresponding number.
  10. List of random numbers was generated at the coordinating center using the permuted bloc method.
  11. Treatment allocation was concealed from the investigators, staff at the trial sites, trial monitors, data analysts, managers, and the patients.
  12. Patients were given the trial medication after undergoing radiotherapy.
  13. One milliliter of the medication was applied to the oral mucosa using a syringe, and patients were instructed to swirl the medication around in the mouth for approximately 15 seconds and then spit. Procedure was repeated after five minutes.
  14. On each treatment day, oromucosal pain was assessed by the patient using the Likert scale, done before dosing and at 5 and 30 minutes, and one, two, three, six, and eight hours post dose.

Sample Characteristics:

  • N = 38 participated (All completed the trial, and no patients discontinued.)
  • MEDIAN AGE = 52 years (range = 2–72 years)
  • MALES: 84.2%, FEMALES: 15.8%
  • KEY DISEASE CHARACTERISTICS: Newly diagnosed head and neck cancer

Setting:

  • SITE: Five oncology centers
  • LOCATION: Bulgaria

Phase of Care and Clinical Applications:

  • PHASE OF CARE: Treatment
  • APPLICATIONS: Mucositis

Study Design:

Crossover, double-blind, placebo-controlled, single-dose, randomized, proof of concept trial

Measurement Instruments/Methods:

  • World Health Organization (WHO) 5 grade toxicity scale for oral mucositis
  • Likert scale of 0 to 10 for pain

Results:

All patients completed the trial. With both treatments, patients experienced a mean 40% decrease in pain intensity at six hours. Both treatments resulted in significant pain relief within five minutes of application that was evident during the entire eight-hour assessment period. At no time did mean pain ratings or pain intensity difference differ statistically between the two treatments. The mean AUC of pain intensity over time did not differ between the two treatments. All of the analyses of pain intensity outcomes showed a statistically significant clinical center effect, with one center reporting larger pain intensity difference values than others. No reason was offered for this difference.

Conclusions:

The similar treatment effects of CAM2028 with or without benzydamine suggest that benzydamine did not contribute additionally to the reduction of oral mucositis pain compared with the unmedicated CAM2028 control. CAM2028 resulted in immediate and significant pain relief with a duration that was maintained for up to eight hours.

Limitations:

  • Small sample (< 100), split between five centers, and no mention of how many at each center
  • No mention of how the outcome assessor was trained to do the assessments of the mucositis, or who did the assessment
  • Women were over-represented in the group receiving placebo first.
  • One center reported larger pain intensity difference than the others. No reason was offered for this difference.

Nursing Implications:

  • Results differences between centers needed further evaluation.
  • No patients received chemotherapy in this study, so only applicable to radiotherapy treatment.
  • No mention of whether radiation techniques were different between the centers.
  • Study does not tell us who monitored the application of the medications.
  • CAM2028 may not be a suitable vehicle with which to combine benzydamine.
  • Other formulations for extended delivery of benzydamine need to be investigated and studied.

Kazemian, A., Kamian, S., Aghili, M., Hashemi, F. A., & Haddad, P. (2009). Benzydamine for prophylaxis of radiation-induced oral mucositis in head and neck cancers: A double-blind placebo-controlled randomized clinical trial. European Journal of Cancer Care, 18(2), 174–178.

doi: 10.1111/j.1365-2354.2008.00943.x
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Study Purpose:

To evaluate the efficacy of benzydamine oral rinse for prevention of radiation-induced mucositis

Intervention Characteristics/Basic Study Process:

Patients rinsed for 2 minutes four times a day with 15 mL study medication (0.15% benzydamine oral rinse) or identical placebo (in appearance and taste) from the first day of radiation therapy (RT) to the end of treatment. Patients were encouraged to brush their teeth at least twice daily and rinse as necessary with normal saline or sodium bicarbonate. Commercial mouthwashes were prohibited.

Sample Characteristics:

  • The study reported on a sample of 81 patients with a mean age 56.
  • There were 54 females and 27 males.
  • All patients had been diagnosed with head and neck cancer and were scheduled to receive a total external beam RT dose of at least 50 Gy in standard fractions and at least 2 oral or oropharyngeal sites were included in the planned RT treatment volume.

Setting:

The study was conducted at the Radiation Oncology Department of the Cancer Institute at Tehran University of Medical Sciences in 2004-2005.

Study Design:

This was a double-blind, randomized, placebo-controlled trial.

Measurement Instruments/Methods:

  • Patients oral hygiene before and during RT (number of tooth brushing per day) was recorded.
  • The Radiation Therapy Oncology Group (RTOG) grading system was used.
  • Patients were visited once.

Results:

  • The statistical analysis revealed that three variables significantly affected the grade of mucositis at the end of the treatment: smoking before and during RT (p = 0.008), chemoradiation (p = 0.002), and receiving benzydamine (p = 0.001).
  • Benzydamine produced a statistically significant reduction in mucositis during RT (p < 0.001).
  • An increase in the grade of mucositis in the first three weeks of treatment was found in both groups, but, after that time, a remarkable difference was found in this parameter in the two groups. Overall, mucositis scores increased rapidly in severity between the third and seventh week of treatment, with a plateau occurring near the end of RT in the placebo group. In the benzydamine group, the plateau appeared from the third week to the end of therapy.

Conclusions:

Benzydamine 0.15% oral rinse was safe and well tolerated. It significantly reduced RT-induced mucositis, which also decreased the interruption of treatment.

Limitations:

  • The study was conducted at a single institution.
  • The sample size was small, with fewer than 100 patients.
  • The authors did not address who conducted the mucositis assessment, opening up the possibility for discrepancy between the evaluators.

Nursing Implications:

Nurses will need to know how to effectively teach patients to use the oral rinse. This study also highlights the importance of daily oral hygiene, which is another good teaching point.

Rastogi, M., Khurana, R., Revannasiddaiah, S., Jaiswal, I., Nanda, S.S., Gupta, P., . . . Bhatt, M.L. (2016). Role of benzydamine hydrochloride in the prevention of oral mucositis in head and neck cancer patients treated with radiotherapy (> 50 Gy) with or without chemotherapy. Supportive Care in Cancer. Advance online publication. 

doi: 10.1007/s00520-016-3548-9
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Study Purpose:

To evaluate the role of benzydamine in the prevention of mucositis in patients receiving more than 50 Gy of radiation therapy

Intervention Characteristics/Basic Study Process:

Patients were stratified according to receiving radiotherapy or radiotherapy and chemotherapy, and then randomly assigned to control or treatment with benzydamine. All patients were advised to use saline mouth rinses, and those in the treatment group also used 0.15% benzydamine hydrochloride rinse. Both groups were to rinse and gargle with the mixture four to six times daily. Patients were examined weekly until four weeks after completion of the treatment.

Sample Characteristics:

  • N = 120   
  • AGE RANGE = 19–90 years
  • MALES: 87.5%, FEMALES: 12.5%
  • CURRENT TREATMENT: Radiation, combination radiation and chemotherapy
  • KEY DISEASE CHARACTERISTICS: All had head and neck cancer.
  • OTHER KEY SAMPLE CHARACTERISTICS: Radiotherapy dosages ranged from 56–70 Gy.

Setting:

  • SITE: Single site   
  • SETTING TYPE: Outpatient    
  • LOCATION: India

Phase of Care and Clinical Applications:

PHASE OF CARE: Active antitumor treatment

Study Design:

Randomized, controlled trial

Measurement Instruments/Methods:

  • Common Terminology Criteria for Adverse Events (CTCAE) toxicity, version 4
  • World Health Organization (WHO) mucositis grading scales

Results:

Patients receiving radiotherapy alone who used benzydamine had a lower prevalence of grade 3 mucositis compared to controls (p = 0.038); however, control patients receiving only radiotherapy also had a longer duration of radiation treatment (p = 0.042, 56 versus 44 days). No significant difference in mucositis outcomes occurred among those receiving both chemotherapy and radiation. Control patients in this group had a longer duration of radiation therapy.

Conclusions:

Benzydamine prophylaxis appears to be effective to reduce the severity of oral mucositis among patients receiving radiotherapy alone for head and neck cancer. Effects for patients receiving both chemotherapy and radiation therapy were not seen.

Limitations:

  • Baseline sample/group differences of import
  • Risk of bias (no blinding)
  • Measurement/methods not well described
  • Exact measure used in analysis and timing of measurement used not stated
  • In both treatment types, patients in the control group had a significantly longer duration of radiation therapy.

Nursing Implications:

Oral rinses with benzydamine were helpful to reduce the prevalence of severe mucositis among patients receiving radiation therapy for head and neck cancer. It is unclear if benzydamine can also be helpful for patients receiving combination chemotherapy and radiation therapy.

Roopashri, G., Jayanthi, K., & Guruprasad, R. (2011). Efficacy of benzydamine hydrochloride, chlorhexidine, and povidone iodine in the treatment of oral mucositis among patients undergoing radiotherapy in head and neck malignancies: A drug trail. Contemporary Clinical Dentistry, 2, 8–12.

doi: 10.4103/0976-237X.79292
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Study Purpose:

To manage oral mucositis induced by radiotherapy and to reduce pain by using benzydamine hydrochloride, chlorhexidine, and povidone iodine

Intervention Characteristics/Basic Study Process:

Selected patients were divided into study and control groups. The study groups were further subdivided into group 1, group 2, and group 3. Each study group consisted of 25 patients, and the control group also consisted of 25 patients; the three study groups and the control group were given benzydamine hydrochloride, chlorhexidine, povidone iodine, and distilled water, respectively. These rinses were given after two weeks of radiation therapy (RT) at the onset of oral mucositis.

Patients in the study groups as well as the control group were instructed to rinse the oral cavity with 15 ml of their respective rinses for at least 30 seconds, 4 times a day at six-hour intervals. The mouth-rinsing regimen was performed under professional supervision. The samples of mouth rinses were given to the patients without dilution for one week use, one at a time, for convenience. Patients also were given measuring cups to measure the quantity of oral rinses. All patients were examined at the end of every week during the RT for about a six-week period.

Sample Characteristics:

  • Patients' age ranged from 30–70 years old.
  • Patients all had head and neck malignancies (no explanation offered).

Setting:

The study was conducted at the Radiotherapy Department of Kidwai Memorial Institute of Oncology in Bangalore, Karanataka, India.

Phase of Care and Clinical Applications:

Patients were undergoing the active treatment phase of care.

Study Design:

The study did not involve blinding.

Measurement Instruments/Methods:

  • The World Health Organization Grading scale for mucositis was used.
  • The Lindquist/Hickey scale was used to evaluate pain.

Conclusions:

This study was oorly designed, and the report was confusing and difficult to understand.

Limitations:

  • No explanation was given as to how the groups were divided into study and control.
  • The authors were unclear as to whether the groups were all given the same mouth rinses or different ones.
  • No blinding was involved.
  • This was a single institution study.
  • No randomization was noted in the report.
  • No mention was made of how compliance was tracked during the study.
  • No age breakdown was given.
  • The authors did not identify who conducted the oral assessments and what training they received to ensure consistency.
  • No mention was made of whether opioids were permitted during treatment for pain control.

Nursing Implications:

Several studies have pointed in the direction that benzydamine hydrochloride is effective in the management of oral mucositis. Further well-designed, randomized placebo controlled studies are needed for verification.

Sheibani, K.M., Mafi, A.R., Moghaddam, S., Taslimi, F., Amiran, A., & Ameri, A. (2015). Efficacy of benzydamine oral rinse in prevention and management of radiation-induced oral mucositis: A double-blind placebo-controlled randomized clinical trial. Asia-Pacific Journal of Clinical Oncology, 11, 22–27.

doi: 10.1111/ajco.12288
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Study Purpose:

To assess the efficacy of prophylactic benzydamine in an oral solution for reducing the signs and symptoms of oral mucositis in patients receiving radiation therapy (RT) with or without chemotherapy for head and neck cancers

Intervention Characteristics/Basic Study Process:

A 0.15% benzydamine or placebo oral rinse of 15 ml was used for two minutes four to eight times daily starting the day before RT and continuing till two weeks RT completion.

Sample Characteristics:

  • N = 51  
  • MEAN AGE = 52.65 years
  • MALES: 60.8%, FEMALES: 39.2%
  • KEY DISEASE CHARACTERISTICS: Head and neck cancer
  • OTHER KEY SAMPLE CHARACTERISTICS: Adults receiving at least 5,000 cGy RT via megavoltage treatment with either cobalt 60 or a linear accelerator to at least two oral mucosal sites with a Karnofsky Performance Status (KPS) > 60

Setting:

  • SITE: Single site    
  • SETTING TYPE: Not specified    
  • LOCATION: Jorjani Cancer Center at the Shahid Beheshti University of Medical Sciences in Tehran, Iran (2009–2012)

Phase of Care and Clinical Applications:

  • PHASE OF CARE: Active antitumor treatment

Study Design:

Randomized, double-blinded, placebo-controlled trial stratified according to KPS and treatment schedule (once- or twice-daily fraction) and then randomized

Measurement Instruments/Methods:

  • The oral cavity was divided into 14 anatomical sites.  
  • A complete oral examination was done weekly after the initiation of treatment, and a four-point scale was used to score each oral site.  
  • At each weekly visit, an overall mean score was calculated based on at-risk areas.

Results:

No difference in the severity of mucositis was found during weeks 1–3. By week 4, the placebo arm had significantly more mucositis than the treatment arm (p = 0.01), and this trend continued until the end of treatment. The difference in the mean score at one and two weeks after treatment continued to show lower scores in the treatment group, but this was nonsignificant.

Conclusions:

An oral rinse of benzydamine 0.15% was safe and well-tolerated with no noticeable side effects reported by patients. It reduced the incidence and severity of radiation-induced oral mucositis.

Limitations:

  • Small sample (< 100)
  • Risk of bias(sample characteristics)
  • Unintended interventions or applicable interventions not described that would influence results
  • Measurement validity/reliability questionable
  • Other limitations/explanation: Single site; unable to analyze data regarding analgesic consumption because of noncompliance; unclear who did the oral examination and training to ensure interrater reliability

Nursing Implications:

Benzydamine was well-tolerated, easy to administer, and may be an appropriate prophylactic treatment for oral mucositis in patients receiving RT for head and neck cancer.

Systematic Review/Meta-Analysis

Kwong, K.K. (2004). Prevention and treatment of oropharyngeal mucositis following cancer therapy: Are there new approaches? Cancer Nursing, 27(3), 183–205.

doi: 10.1097/00002820-200405000-00003
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Search Strategy:

Database searched was MEDLINE (1993–2003) for randomized, controlled trials evaluating mucositis interventions.

Literature Evaluated:

A total of 50 randomized controlled trials were presented. Other trials and papers were referenced.

Sample Characteristics:

  • Sample sizes ranged from 10–222.
  • Patients were treated with chemotherapy, radiotherapy, and bone marrow transplantation.

Conclusions:

The author concluded that most agents require more study.

  • Evidence for cryotherapy and bolus 5-fluorouracil was strong.
  • Sucralfate studies produced conflicting results and included varying doses and administration frequencies, making comparisons difficult. Most studies indicated no difference in severity or duration. The validity and reliability of the data were questioned because of the measurement scales used.
  • Similarly, studies of cytokine-like agents used different doses, making comparisons difficult.
  • Moderate evidence suggested that benzydamine is effective in relieving mouth pain caused by radiation-induced mucositis in patients with head and neck cancer. The agent requires additional investigation and study for chemotherapy-induced mucositis.
  • Large studies of chlorhexidine mouthwashes have failed to show significant findings; however, the studies may have had inadequate sample sizes, as power analyses were not performed.
  • Povidone-iodine showed significant reduction in onset, incidence, total duration, and worst grade of mucositis for patients with head and neck cancer undergoing radiation with carboplatin in two studies. Both studies had sample sizes of 40. Given these sample sizes and specific populations, generalizability of the findings was restricted.
  • Oral hygiene protocols were shown to reduce the duration and severity of mucositis; however, the content of the protocols was not proven.

Limitations:

The author noted the problem of variation in study protocols, insufficient sample sizes, and a lack of consensus regarding the scoring system for mucositis.

Nursing Implications:

The author noted the need to include psychotherapeutic interventions and management and pointed out the lack of a quality-of-life tool for mucositis.

Shih, A., Miaskowski, C., Dodd, M. J., Stotts, N.A., & MacPhail, L. (2002). A research review of the current treatments for radiation-induced oral mucositis in patients with head and neck cancer. Oncology Nursing Forum, 29, 1063–1078.

doi: 10.1188/02.ONF.1063-1080
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Search Strategy:

Database searched was MEDLINE (1966–2001). Additional papers were found from reference lists.

Studies were included in the review if they were aimed at prevention, palliation, or reduction of radiation-induced oral mucositis in patients with head and neck cancer.

Studies were excluded if they were not in English.

Literature Evaluated:

More than 50 studies were included. Most were randomized, controlled trials; some were pilot or descriptive studies. 

Sample Characteristics:

Sample sizes ranged from 10 to more than 200.

Conclusions:

Based on the findings of studies conducted to date, no conclusions regarding the agents and their ability to decrease the severity of radiation-induced oral mucositis were possible. Results were inconsistent. The most effective measure to treat radiation-induced mucositis was frequent oral rinsing with a bland mouthwash such as saline or sodium bicarbonate. Consistent oral care, dental care, oral assessment, and standardized oral hygiene were the suggested approaches to managing oral mucositis. Sodium bicarbonate reduces the acidity of the oral fluids immediately; it also dilutes accumulating mucus and discourages yeast colonization.

Findings related to benzydamine were inconsistent. In a trial of chlorhexidine versus benzydamine, patients reported more discomfort with benzydamine and were more likely to discontinue participation in the trial. Chlorhexidine was not effective in reducing the severity of mucositis in three double-blind, placebo-controlled trials. Two trials that examined antimicrobial activity failed to show any significant effects on the suppression of any type of oral flora using chlorhexidine.

Dose variations in granulocyte macrophage colony-stimulating factor (subcutaneous) trials make it impossible to determine whether this agent has a role in the radiation setting.

Four studies investigated the effectiveness of using topical antibiotics with a more specific spectrum for gram-negative bacteria and yeast. Two placebo-controlled, randomized clinical trials, both with fewer than 100 patients, and one case-controlled study investigated the efficacy of amphotericin B (polymyxis E, tobramycin, and amphotericin B [PTA] lozenge) to reduce the severity of radiation-induced mucositis. One study examined tetracaine and antibiotics. Additional work is warranted to determine the effects of the PTA lozenge on mucositis severity, pain severity, and dysphagia. Results for the trial were promising; however, conclusions cannot be drawn because only one study examined tetracaine.

Nursing Implications:

Additional investigation of immunoglobulin and povidone-iodine are recommended.

Guideline/Expert Opinion

Nicolatou-Galitis, O., Sarri, T., Bowen, J., Di Palma, M., Kouloulias, V.E., Niscola, P., . . . Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO). (2013). Systematic review of anti-inflammatory agents for the management of oral mucositis in cancer patients. Supportive Care in Cancer , 21(11), 3179–3189.

doi: 10.1007/s00520-013-1847-y
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Purpose & Patient Population:

PURPOSE: Systematically review literature and define updated clinical practice guidelines regarding use of anti-inflammatory agents

TYPES OF PATIENTS ADDRESSED: Patients receiving chemotherapy or radiation therapy

Type of Resource/Evidence-Based Process:

RESOURCE TYPE: Evidence-based guideline

PROCESS OF DEVELOPMENT: Studies evaluated using Hadorn criteria and assigned levels of evidence on Somerfield criteria by independent reviewers. Findings were integrated into guidelines based on overall level of evidence for each intervention.

DATABASES USED: MEDLINE (1966–December 31, 2010)

KEYWORDS: aminosalicylic acid, amifostine, amlexanox, anti-inflammatory, anti-TNF, anti-tumor necrosis factor, aspirin, Benadryl®, benzydamine, betamethasone, celecoxib, corticosteroid, dexamethasone, diphenhydramine, Ethyol®, flurbiprofen, histamine, hydrocortisone, ibuprofen, indomethacin, infliximab, irsogladine, lactoferrin, mesalazine, misoprostol, N-acetylcysteine, non-steroidal anti-inflammatory agents, NSAIDS, orgotein, prednisone, prostaglandin, RK-02-02, salicylic acid, steroid, thalidomide, TNF antibody, TNF inhibitor, and tumor necrosis factor/TNF

INCLUSION CRITERIA: Articles involving anti-inflammatory agents for prevention or treatment of oral mucositis

Phase of Care and Clinical Applications:

PHASE OF CARE: Active antitumor treatment

Results Provided in the Reference:

Forty-one studies were included in the review involving use of multiple anti-inflammatory agents.

Guidelines & Recommendations:

  • Benzydamine mouthwash is recommended for prevention in patients with head and neck cancer receiving moderate-dose radiation therapy without concomitant chemotherapy.
  • Misoprostol is not recommended for use of prevention of radiation-induced oral mucositis.
  • For all other anti-inflammatory agents, no guidelines were deemed possible due to insufficient evidence.

Limitations:

  • Most evidence reported was from studies of patients with head and neck cancer.
  • Very few studies per individual agent were reviewed, and the level of evidence was low for all but benzydamine.

Nursing Implications:

Two new guidelines were identified by this systemic review. The panel suggests that misoprostol mouthwash should not be used for the prevention of radiation-induced oral mucositis in patients with head and neck cancer. The other new guideline the panel recommends is benzydamine mouthwash for the prevention of oral mucositis in patients with head and neck cancer receiving moderate-dose radiation therapy (up to 50 Gy) without concomitant chemotherapy. In addition to this, the lack of clear evidence supporting the use of any anti-inflammatory agent other than benzydamine, the use of anti-inflammatory agents continues to be a promising strategy for the prevention and treatment of oral mucositis. More well-designed studies are needed to examine the use of anti-inflammatory agents for oral mucositis in various cancer care settings.

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