STUDY PURPOSE: Assess effectiveness of acupressure on chemotherapy-induced nausea and vomiting (CINV)

TYPE OF STUDY: Meta-analysis and systematic review

• DATABASES USED: PubMed, CINAHL, EMBASE, Science Direct, China Biology Medicine, Chinese National Knolwedge Infrastructure, Wan Fang, Database for Chinese Technical Periodicals, Cochrane collaboration
• INCLUSION CRITERIA: Patients on IV chemotherapy, acupressure was used with or without antiemetics, comparisons were antiemetics or nursing care, English or Chinese language
• EXCLUSION CRITERIA: Auricular acupressure

• TOTAL REFERENCES RETRIEVED: 1,326
• EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Cochrane risk of bias assessment; if any item was considered high risk, the study was deemed high risk of bias.

• FINAL NUMBER STUDIES INCLUDED: 12
• TOTAL PATIENTS INCLUDED IN REVIEW: 1,419
• SAMPLE RANGE ACROSS STUDIES: 17-500
• KEY SAMPLE CHARACTERISTICS: Various tumor types. Where reported, chemotherapy was MEC or HEC

PHASE OF CARE: Active anti-tumor treatment

Relative risk for incidence of acute vomiting across five trials was 0.84 in favor of acupressure, but this was not significant (p = 0.08). There was not a significant difference in relative risk with or without acupressure (p = 0.29) (two trials). Acupressure combined with antiemetics decreased nausea severity in the delayed phase (SMD = -0.33, p = 0.04), but there was no significant effect on incidence and frequency of delayed vomiting. P6 was the most frequently used acupoint. Interventions used either a wristband or manual acupressure, and findings for these two approaches differed. Sham control trials did not demonstrate a significant effect.

Acupressure may reduce the severity of nausea, particularly in the delayed phase in patients receiving MEC or HEC

• High heterogeneity
• No description of antiemetics used.

Acupressure might be a useful adjunct to antiemetics for management of CINV.  Findings suggest that this may be helpful to reduce the severity of nausea, which has remained a problem even with maximum antiemetics. Findings of this analysis showed differences with sham controlled trials, suggesting there may be a placebo effect of acupressure.

Recent preclinical and phase I studies have reported that rebamipide decreased the severity of chemoradiotherapy-induced oral mucositis in patients with oral cancer. This placebo-controlled randomized phase II study assessed the clinical benefit of rebamipide in reducing the incidence of severe chemoradiotherapy-induced oral mucositis in patients with head and neck cancer (HNC).

Patients aged 20–75 years with HNC who were scheduled to receive chemoradiotherapy were enrolled. Patients were randomized to receive rebamipide 2% liquid, rebamipide 4% liquid, or placebo. The primary endpoint was the incidence of grade ≥ 3 oral mucositis determined by clinical examination and assessed by central review according to the Common Terminology Criteria of Adverse Events, version 3.0. Secondary endpoints were the time to onset of grade ≥ 3 oral mucositis and the incidence of functional impairment (grade ≥ 3) based on the evaluation by the Oral Mucositis Evaluation Committee.

• N: 97
• AGE: 20–75 years with HNC 
• MALES: 100% 
• CURRENT TREATMENT: Chemotherapy, radiation
• KEY DISEASE CHARACTERISTICS: HNC, oral cavity, nasopharynx, oropharynx, hypopharynx, and larynx

• SITE: Multi-site
• SETTING TYPE: Outpatient
• LOCATION: Japan

• PHASE OF CARE: Active anti-tumor treatment
• APPLICATIONS: Elder care, palliative care

Patients aged 20–75 years with HNC who were scheduled to receive chemoradiotherapy were enrolled. Patients were randomized to receive rebamipide 2% liquid, rebamipide 4% liquid, or placebo.

The incidence of oral mucositis in each group was compared using the chi-square test. A step-down strategy was used for the between-group comparison, adjusting for multiplicity. Comparisons were made first between the rebamipide 4% and the placebo groups, and then between the rebamipide 2% and placebo groups. The Cochran-Armitage test was used as a trend test. All statistical analyses were performed using SAS, version 9.2.

In a trend test, a decrease in the incidence of grade ≥ 3 oral mucositis was observed with an increasing concentration of rebamipide liquid; however, this decrease was not statistically significant (p = 0.2399).

The rebamipide 2% and 4% groups showed a trend of delaying the time to onset of grade ≥ 3 oral mucositis as compared with the placebo group, although the difference between the groups was not statistically significant

A decrease in incidence of grade ≥ 3 oral mucositis in patients treated with rebamipide 2% and 4% compared with those treated with placebo, these differences were not statistically significant.

There was a prolongation in the time to onset of grade ≥ 3 oral mucositis and a decrease in functional impairment in patients treated with rebamipide 4% compared to those treated with placebo; these results may suggest a clinical benefit of rebamipide in reducing the incidence of severe oral mucositis induced by CRT.

• Small sample (< 100)
• Other limitations/explanation: Differenced in oral retention and swallowing compliance for the study drugs between treatment groups.

Systemic oral care alone is insufficient to decrease the incidence of severe oral mucositis. Therefore, there is a strong demand for the development of prophylactic and therapeutic agents against oral mucositis. There is efficacy and safety profiles that suggest rebamipide 4% is safe and effective, although not statistically significant. Further studies are needed using rebamipide 4% for treatment of CRT-induced oral mucositis.

The aim of the study to evaluate the efficacy of a Rebamipide gargle in the prevention and treatment of chemoradiotherapy-induced oral mucositis.

All participants received bottles of gargle and were advised to gargle with 20 ml of gargle, six times a day (breakfast, 11 am lunch, 3 pm dinner, and at bedtime) beginning on the first day of radiotherapy and ending at the completion of radiotherapy. The gargle provided to both groups were identical in ingredients except for the one given to the intervention group, which contained an extra ingredient (Rebamipide). Daily oral exams were conducted at the beginning of radiotherapy and concluded at the end of radiotherapy to determine the onset of oral mucositis.

• N = 60 (n = 30 in intervention and control groups)    
• AGE: 34-75 years
• MALES: 98%    
• FEMALES: 1%
• KEY DISEASE CHARACTERISTICS: Participants were aged 18 years of age or older who were undergoing radiation therapy for newly diagnosed head and neck squamous cell carcinoma.
• OTHER KEY SAMPLE CHARACTERISTICS: 13% had stage I/II cancer and 86% had stage III/IV cancer.

• SITE: Not stated/unknown    
• SETTING TYPE: Not specified  
• LOCATION: Unknown

• PHASE OF CARE: Active anti-tumor treatment
• APPLICATIONS: Elder care, palliative care

Randomized, double-blinded placebo controlled study.

Numeric scale and the RTOG grading system. Statistical methods used were the IBM SPSS Statistics, version 18, with comparison of variables done using an Independent sample t test and Mann-Whitney U test. Chi-square test was used to compare categorical variables.

A statistically significant delay of onset of mucositis of 3.5 days was found in the intervention group as compared to the control group. A statistically significant reduction in numeric and RTOG pain scores were also found in the intervention group as compared to the control group.

Rebamipide gargle is effective in delaying the onset of oral mucositis and in reducing the severity of pain of oral mucositis in patient undergoing chemotherapy and radiation therapy for head and neck cancer.

Small sample (< 100)

CAM 2028 can be effective in treating pain induced oral mucositis from radiation therapy. Benzydamine does not contribute to the reduction of oral mucositis pain.

To evaluate Hypozalix artificial saliva and propolis mouthwash efficacy for the prevention of chemotherapy-induced oral mucositis in patients with leukemia.

Double-blind RCT with patients assigned to three groups. The control group used the CHX mouthwash and fluconazole. Group 1 and 2, Hypozalix and propolis mouthwashes, respectively, added to combination therapy used in control group. Results compared between three groups after 14 days.

• N: 72   
• AGE: 1-71 years
• MALES: Matched  
• FEMALES: Matched
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: Leukemia and chemotherapy
• OTHER KEY SAMPLE CHARACTERISTICS: Starting similar chemotherapy regimens, matched

• SITE: Single site   
• SETTING TYPE: Inpatient    
• LOCATION: Oncology Dept of Shahid Ghazi Hospital in Tabriz

• PHASE OF CARE: Active anti-tumor treatment
• APPLICATIONS: Pediatrics, elder care

Double-blind RCT, one control and two intervention groups.

Descriptive two-part questionnaire checklist and OM severity checklist. The tool used to collect data was a two-part questionnaire and a checklist to determine the severity of mucositis. The two-part questionnaire was used to collect demographic data (age and gender) and consisted of questions on the type of disease, history of chemotherapy, presence or absence of systemic disease other than malignancy, and the presence or absence of skin or respiratory allergy. The second part of the questionnaire consisted of questions on the severity of xerostomia, ease of mastication and swallowing, the severity of burning sensation, the quality of sleep during the night, and the tendency to continue to use the medications; the patients completed this part before and after the intervention. In addition, in order to determine the severity of oral mucositis, a checklist was used, which was designed based on the criteria of WHO; based on these criteria, oral mucositis is divided into five distinct grades from 0 to 4.17. To determine validity of the questionnaire, content validity method was used. To determine reliability of the questionnaire, simultaneous observation technique was used. To this end, observations were carried out by two observers with similar characteristics, using similar guidelines on 10 samples, which yielded a correlation coefficient of 0.94. Then, the questionnaire was completed using interviews and patient files.

After 14 days, 50% of patients in the control group (CHX mouthwash and fluconazole) exhibited signs of recovery from xerostomia. For group 2 (propolis mouthwash and CHX mouthwash and fluconazole), 50% of patients exhibited some signs of recovery from xerostomia. 95.8% patients in group 1 (CHX mouthwash and fluconazole and Hypozalix spray) reported recovery from xerostomia. Chi-squared test statistically significant (p = 0.0006). At the end of the study, 29.17% in control group, 87.5% in group 1, and 70.83% in group 2 exhibited easy mastication. Chi-squared test significant statistically (p = 0.0001). 33.3% in control group, 63.3% in group 1, and 87.5% of patients in group 2 exhibited easy swallowing. Chi-squared test statistically significant (p < 0.0001). At end of study, 33.3% in control group, 58.3% in group 1, and 91.6% in group 2 were interested in continuing to use the product. Chi-squared test statistically significant (p = 0.0002). 16.67% of patients in control group, 25% in group 1, and 62.5% in group 2 exhibited more full night’s sleep and less waking up. Chi-squared test statistically significant (p = 0.0018). In relation to an improvement in oral burning sensation, 8.33% of patients in control group, 25% in group 1, and 91.67% in group 2 exhibited decrease in burning sensation. Chi-squared test significant statistically (p < 0.0001). 62.5% of patients in control group, 62.5% in group 1, and 95.8% in group 2 had a higher rate of feeling comfortable. Chi-squared test was significant (p = 0.0103). A clinical examination of patients five days after using the medications showed 8.33% of patients in control group, 12.5% in group 1, and 50% in group 2 were free of mucositis. However, 25% of patients in control group and 16.6% in group 1 had grade 4 mucositis. None in group 2 exhibited grade 4 mucositis. Chi-squared test significant (p = 0.0007). A clinical examination of patients 10 days after using the medications showed 25% of patients in control group, 33.3% in group 1, and 50% in group 2 were free of mucositis. 12.5% of patients in control group and 4.17% in group 1 had grade 4 mucositis. None in group 2 had grade 4 mucositis. However, chi-squared test indicated that the difference was not statistically significant (p = 0.1135).

50% of patients in control group, 95.8% of patients who received Hypozalix, and 50% who received Propolis exhibited decrease in xerostomia severity. 29.17% of patients in control group, 87.5% in Hypozalix group, and 70.83% in Propolis group exhibited easy mastication. 33.3% of patients in control group, 63.3% of patients in Hypozalix group, and 87.5% of patients in Propolis group exhibited easy swallowing. 91.6% of patients in propolis group were interested in continuing to use product. The lowest tendency was seen in control group patients, followed by those in Hypozalix group. 62.5% of patients in propolis group exhibited less waking up at night and 95.8% of them had a higher rate of feeling comfortable. The lowest burning sensation was detected in that group. Propolis resulted in significantly greater decrease in severity of mucositis compared to Hypozalix and control group five days after using medications. These contradictory results might be attributed to differences in study designs and in Propolis origins. In many cases, use of Propolis mouthwash yielded significantly better results, and patients exhibited a greater tendency to continue to use it. If results of this study are confirmed by other studies, treatment with Propolis can reduce secondary oral infections and mucositis caused by chemotherapy. Since Propolis and Hypozalix had positive effects on decreasing mucositis induced by chemotherapy in this study, toothpastes may be designed with propolis base. Hypozalix spray or propolis mouthwash in association with CHX mouthwash and fluconazole simultaneously at the start of chemotherapy resulted in decrease in chemotherapy complications after 14 days. Propolis mouthwash yielded better results and the patients exhibited greater tendency to continue to use it.

• Small sample (< 100)
• Other limitations/explanation: Small study with limitations in descriptive measurement.

To assess the impact of saline mouth rinse regimen and education program on radiation-induced OM symptoms and QOL in patients with oral cavity cancer receiving RT or CCRT.

Ninety‐one OCC patients were randomly divided into a group that received saline mouth rinses and an education program and a control group that received standard care. OM symptoms and QOL were assessed with the WHO Oral Toxicity Scale, MSS‐moo, and UW‐QOL. Data were collected at the first postoperative visit to the radiation department (T0) and at 4 weeks and 8 weeks after beginning RT or CCRT.

• N: 91   
• AGE: 20 years or older
• MALES: 93.8%  
• FEMALES: 6.2%
• CURRENT TREATMENT: Radiation, combination radiation and chemotherapy  
• KEY DISEASE CHARACTERISTICS: Diagnosed with oral cavity cancer
• OTHER KEY SAMPLE CHARACTERISTICS: Undergoing postoperative adjuvant RT or CCRT

• SITE: Single site   
• SETTING TYPE: Outpatient    
• LOCATION: Cancer center in northern Taiwan

• PHASE OF CARE: Active anti-tumor treatment
• APPLICATIONS: Elder care

Double-blind RCT one control and two intervention groups.

OM symptoms and QOL were assessed with the WHO Oral Toxicity Scale, MSS‐moo, and UW‐QOL. Data were collected at the first postoperative visit to the radiation department (T0) and at 4 weeks and 8 weeks after beginning RT or CCRT.

Patients in both groups had significantly higher levels of physical and social‐emotional QOL at 8 weeks after beginning RT or CCRT compared to the first visit. Patients in the saline rinse group had significantly better physical and social‐emotional QOL as compared to the standard care group at 8 weeks. Radiation‐induced OM symptoms and overall QOL were not different between the groups.

The authors concluded that the saline rinse and education program promote better physical and social‐emotional QOL in OCC patients receiving RT/CCRT. The results of this study indicated that saline mouth rinses with an education program were effective in increasing physical and social‐emotional QOL by improving the radiation‐induced OM symptoms and promoting oral comfort in patients receiving RT/CCRT for HNC, as compared to standard care. However, no improvement in radiation‐induced OM symptoms and overall QOL was found.

• Small sample (< 100)
• Other limitations/explanation: Small study with limitations in descriptive measurement.

It might be helpful to provide and teach saline mouth rinses to patients

To evaluate the efficacy and route of administration of omega-3 fatty acids for the prevention and treatment of oral mucositis.

Patients were randomized to omega-3 (two capsules daily with meals, each capsule contained 2,000 mg of fish oil plus EPA/DHA). The placebo contained corn oil with EPA/DHA.

• N = 30 control group, 30 in the omega 3-fatty acid intervention group  
• AGE: 22-63 years old
• MALES: 23 (38%)  
• FEMALES: 37 (62%)
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: Leukemia or breast cancer diagnosis 
• OTHER KEY SAMPLE CHARACTERISTICS: Patients were actively undergoing chemotherapy treatments with WHO grade I mucositis and were not to be treated with chemical agents.

• SITE: Single site   
• SETTING TYPE: Not specified    
• LOCATION: Kerman, Iran

• PHASE OF CARE: Active anti-tumor treatment
• APPLICATIONS: Elder care, palliative care

Double-blinded random control study

Mucositis was evaluated based on the WHO, Oral Mucositis Weekly Questionnaire (OMPQ), and Western Consortium for Cancer Nursing Research (WCCNR) criteria.

At 1 and 2 weeks, the severity of mucositis was lower in the omega-3 group compared with the control group and, after 2 weeks, there was no evidence of mucositis in the patients taking omega-3. Patients taking omega-3 compared with the placebo exhibited a better ability to eat, and the difference between the two groups was statistically significant (p = 0.002). The average duration of mucositis in the omega-3 group was 5.5 days and in the placebo groups, 10-12 in the placebo group. The mean pain intensity scores during the first 24 hours were 5 ± 5.4 and 8 ± 6.4 in the omega-3 and placebo groups, respectively. The maximum and minimum values of pain severity scores in the omega-3 group were 6 and 0 in the placebo group. The patients’ quality of life in both groups showed a statistically significant difference in weeks 2 and 3 (p = 0.01).

Omega-3 fatty acids show promise in reducing the severity and duration of mucositis as well as the associated pain intensity.

• Small sample (< 100)
• Other limitations/explanation: Only two types of diagnosis breast cancer and leukemia were included.

These results show promise for treating patients with oral mucositis with omega-3 fatty acid.

To compare between LLLT and placebo for overall disease-free survival (DFS) and progression-free survival (PFS) of patients with head and neck cancer who received chemoradiation therapy. Randomized double-blinded placebo controlled phase III trial

Patients received low-level laser therapy or placebo; LLLT with an InGaAIP diod (660 nm to 100 mW-1 J-4J/cmsq, and a spot size of 0.24 cm² five days a week before radiotherapy. contact with the mucosa on nine points per region for 10 seconds per point, totaling 12 minutes per patient for LLLT.

• N: 94; laser group = 47, placebo group = 47    
• AGE: Mean age of LG = 53.5, PG = 55.7; non-significant
• MALES: LG male, 89.4%; PG male, 85.1%    
• FEMALES: LG female, 10.6 %; PG female, 14.9%
• CURRENT TREATMENT: Combination radiation and chemotherapy
• KEY DISEASE CHARACTERISTICS: Head and neck cancer (nasopharynx, oropharynx, and hypopharynx cancer)

• SITE: Not stated/unknown Instituto Nacional de Câncer (INCA)
• SETTING TYPE: Not specified    
• LOCATION: Rio de Janeiro Brazil

PHASE OF CARE: Active anti-tumor treatment

Randomized phase III trial of patients with head and neck cancer. Details of randomization not provided.  

Both group received treatments of chemotherapy (cisplatin 100 mg/m² at day 1, 22, and 43) and radiotherapy according to tumor localization, using megavoltage radiotherapy with 2D and 3D techniques. A total dose of 70.2 Gy daily in 39 fractions, five days a week, using a cobalt-60 and a linear accelerator unit.

The adverse effects were evaluated daily, according to the Common Toxicity Criteria, version 3.0, from the National Cancer Institute (NCI-CTC) [16]. Oral mucositis was evaluated every day during the treatment period, according to the OMS and OMAS scales. The modified visual analog scale was used to evaluate pain. Body weight (body mass index) was measured every week. Patients were evaluated by a complete physical examination, oroscopy, nasopharyngoscopy, hematologic and biochemical profiles, chest radiography, and CT/MRI performed every four months for the first two years, every six months from the third to the fifth year, and then annually according to the RECIST criteria.

• Overall survival: LG 57.4% versus PG 40.4%; p = 0.9 NS; HR = 1.64; 95% CI [0.92, 2.91]
• DFS: PG 65.9% versus 58.6%; p = 0.659 NS; HR = 1.19; 95% CI [0.55, 2.57]
• PFS*: 61.7% versus 40.4%; p = 0.03; HR = 1.93; 95% CI [1.07, 3.5] 
• OM stage 3-4*: LG 6.3% versus PG 48% (p < 0.001)
• Gastrostomies*: LG 14.9% versus PG 38.3%; RRR = 0.39 (95% CI [0.18, 0.84]), p = 0.01
• Complete chemotherapy interruption: LG 12.8% versus PG 19.1%
• Chemotherapy dose reduction: LG 2.1% versus PG 6.4%
• Opioid use*: LG = 31.9% versus PG = 85.1; RRR = 0.38 (95% CI [0.24, 0.58]; p < 0.001
• Temporary radiotherapy interruption due to radiodermatitis: LG 14.9% versus PG 8.5%

* statistically significant findings.

Laser group had better progression-free survival and complete response, however this did not carry over to overall survival significance. Oral mucositis severity was statistically significantly lower in LLLT group.

• Small sample (< 100)
• Unintended interventions or applicable interventions not described that would influence results
• Subject withdrawals ≥ 10%
• Other limitations/explanation: Limited information in article regarding original study, so do not have many details that would be helpful

LLLT was beneficial to reduce oral mucositis. No statistically significant results for overall survival is likely affected by type II error (small sample size), and larger sample size study is needed. This study found statistically significant improvement for progression-free survival and LLLT may improve not only mucositis occurrence/severity but also patients’ survival.

To evaluate if Shaunghaubaihe tablets can prevent oral mucositis for patients with locally advanced nasopharyngeal carcinoma undergoing chemoradiotherapy.

Multi-site, randomized, double blind study of Shuanghuabaihe tablets versus placebo (four tablets, three times a day) started at the initiation of chemoradiotherapy and lasting seven weeks. Patients could stop taking the tablets if grade 3 mucositis developed.

• N = 240   
• AGE: 18-70 years old 
• MALES: 70% (intervention) and 63.03% (placebo)  
• FEMALES: 30% (intervention) and 36.97% (placebo)
• CURRENT TREATMENT: Combination radiation and chemotherapy
• KEY DISEASE CHARACTERISTICS: Nasopharyngeal carcinoma

• SITE: Multi-site   
• SETTING TYPE: Not specified    
• LOCATION: China

PHASE OF CARE: Active anti-tumor treatment

RCT. Patients age 18-70 years with locally advanced nasopharygeal carcinoma randomly assigned to receive Shaunghaubaihe tablets or a placebo, starting at the initiation of chemoradiation.

The incidence of different stages of mucositis was compared using Fisher’s exact test and the 95% confidence intervals. The Kaplan-Meier method was used to estimate the median time of the occurrence of OM (latency). To compare latency, the Cox proportional hazard model was used for hazard ratio (HR) and 95% CI values. One-way ANOVA and Fisher’s exact were used to compare toxicities and secondary efficacy endpoints. All data was analyzed using SAS, version 9.2, software.

Shaunghaubaihe tablets significantly reduced the incidence, latency, and severity of oral mucositis in patients with nasopharyngeal cancer.

Two patients from placebo and eight from treatment arm did not complete the entire course of radiation therapy. This is an initial study and further clinical study is needed to evaluate and verify therapeutic effects.

Therapeutic agents that prevent oral mucositis are needed because systemic oral care alone is insufficient.

To estimate the efficacy of traditional Chinese medicine (Chining decoction, CHIN) for radiation-induced oral mucositis in patients with head and neck cancer.

70 consecutive patients were randomly assigned to receive CHIN (treatment group) or recombinant human epidermal growth factor (rhEGF) spray (control group) at a 1:1 ratio in the period between May 2014 to December 2015. CHIN was administered to treatment group from the first day of radiotherapy until the completion of radiotherapy. Simultaneously, the rhEGF spray was administered to control group on the oral mucosa of the irradiated area. The clinical benefit was determined by gradation of mucositis (Common Terminology Criteria for Adverse Events, version 4.0), oral pain, and xerostomia (visual analysis scale) for each week during radiotherapy. Body mass index was evaluated before and after radiotherapy.

• N = 70   
• AGE: 17-76
• MALES: 76%  
• FEMALES: 24%
• CURRENT TREATMENT: Radiation
• KEY DISEASE CHARACTERISTICS: Head and neck cancer
• OTHER KEY SAMPLE CHARACTERISTICS: No history of oral ulcer and salivary gland diseases, No history of anti-tumor therapies.

• SITE: Single site   
• SETTING TYPE: Inpatient    
• LOCATION: China

PHASE OF CARE: Active anti-tumor treatment

Prospective control randomized trial

• The National Cancer Institute Common Toxicity Criteria Oral Mucositis Scale.
• Oral pain and xerostomia were assessed by the patients with the visual analysis scale (VAS).
• Body mass index (BMI) was used to assess the nutritional status of patients before and after treatment.

• Patients in the treatment group had prominent remission of oral pain and grade of mucositis on each observing point compared with those in control group (p < 0.01).
• Xerostomia was decreased notably in treatment group compared with control group (p < 0.01).
• The degrees of OM in the treatment group were 1.57 (SD = 0.51) versus 2.49 (SD = 0.7) in the control group (p < 0.01).

CHIN presented an obvious advantage in preventing radiation-induced oral mucositis compared with rhEGF spray.

• Small sample (< 100)
• Risk of bias (no control group)