To determine the effectiveness of standardized bioactive compound of ginger extract (6-Gingerol) on CINV in solid tumor patients receiving MEC to HEC in addition to standard antiemetics (ondansetron, metoclopramide, and dexamethasone) in solid tumor patients

Patients were randomized to receive 10 mg ginger extract capsule (6-gingerol) or a matching placebo twice daily three days before prior to chemotherapy to D1 and continued for 12 weeks; in addition to standard antiemetics. For HEC regimen, D1 (ondansetron 8 mg IV plus dexamethasone 12 mg IV) and oral daily on days 2 to 4. For MEC regimen, D1 (ondansetron 8 mg IV plus dexamethasone 8 mg IV) and oral daily on days 2 to 4. All patients received metoclopramide 10 mg orally three times daily on days 2 to 4. Rescue antiemetics were allowed at any time. Intensity of nausea and appetite was measured daily by the numeric rating scale. Also, patients recorded nausea and vomiting events daily from day 0 to 120 hours after each chemotherapy cycle. QOL measured by (FACT-G) instrument at days 1, 22, 43, and 64 of treatment.

• N = 96; 81 patients remained for analysis (excluded before initial treatment or on week 1)   
• AGE: median = 53 years (range = 19-81) 
• MALES: 7%  
• FEMALES: 93%
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: Solid tumor, older than age 18 years, newly diagnosed 
• OTHER KEY SAMPLE CHARACTERISTICS: Scheduled to receive three consecutive chemotherapy cycles after surgical resection, not on NK1 RA regimen

• SITE: Multi-site   
• SETTING TYPE: Inpatient    
• LOCATION: Thailand

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

Multicenter randomized, double-blind, placebo-controlled phase II study

Intensity of nausea and appetite was measured daily by the numeric rating scale using the Edmonton Symptom Assessment Scale (ESAS), ranging from 0 to 10. Quality of life will be measured by using version 4 of the Functional Assessment of Cancer Therapy-General (FACT-G). Daily diary from days 1-5 in each chemotherapy cycle (this includes number of vomiting episodes, nausea score, appetite score, QOL, use of rescue antiemetic, and hospitalization).

The overall CR rate was significantly higher in patients treated with 6-gingerol compared with placebo (p = 0.001) in both acute (p = 0.003) and delayed (p = 0.001) phases. However, during the first chemotherapy cycle, there was no statistically significant differences. Patient received 6-gingerol reported improvement in appetite (p = 0.001) and less severity of overall nausea p < 0.001 and statistical improvement in QOL (p < 0.001) compared to placebo. Ginger was well tolerated with no observed adverse effect.

Prolonged and continuous daily dosing of 6-gingerol appears to be effective. 6-gingerol improved patient’s appetite and QOL; it is safe and well tolerable

• Small sample (< 100)
• Intervention expensive, impractical, or training needs
• Subject withdrawals ≥ 10%

Ginger is safe and well tolerable complementary therapy for patient on MEC-HEC. It also improve patient appetite and QOL.

To determine the effectiveness of ginger on the incidence and intensity of delayed nausea for patients on HEC (cisplatin)

Patients scheduled to receive high-dose cisplatin for two or more chemotherapy cycles were randomized to receive standardized ginger preparation 120 mg per day [two capsules of 40 mg twice daily] (16 mg gingerols plus 1.12 mg shogaoil) or placebo in addition to standard antiemetics (NK1 RA and 5-HT_³ RA on day 1 and dexamethasone on days 1-4) for a period of two chemotherapy cycles; nearly 45 days.

• N = 244 patients (121 ginger; 123 placebo)    
• AGE: Mean = 59.2 years
• MALES: 65.6% (ginger 68.6%, placebo 62.6%)  
• FEMALES: 34.4% (ginger 31.4%, placebo 37.4%)
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: Chemotherapy naïve, solid tumor (lung, head and neck cancer, planned to receive two or more cycles of > 50 mg cisplatin) 
• OTHER KEY SAMPLE CHARACTERISTICS: No ANV before fist HEC cycle

• SITE: Multi-site   
• SETTING TYPE: Inpatient    
• LOCATION: Six Italian oncology centers

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

Randomized, double-blind, placebo-controlled

Visual analog scale, 0–100 mm for nausea incidence and intensity, Functional Living Index Emesis (impact of nausea am daily living), Brief Fatigue Inventory questionnaire (impact of fatigue)

No significant differences between the two groups in relation to incidence of delayed nausea, intercycle nausea, and anticipatory nausea during the first and second cycle. In ginger group; men with lung cancer experienced a higher incidence of significant delayed and intercycle nausea (p < 0.05), incidence of delayed nausea was higher among patients with lung cancer in the ginger group than placebo (p = 0.042), no differences in FLIE and BFI between the two groups; a benefit of ginger over placebo in terms of FLIE for female versus male patients and in head/neck cancer versus lung cancer. No differences in experienced adverse effects between the two groups.

Ginger had no beneficial effect in reducing CINV (delayed, anticipatory, and intercycle) associated with HEC.

• Measurement validity/reliability questionable 
• Findings not generalizable
• Intervention expensive, impractical, or training needs
• Other limitations/explanation: No stratification for the gender and the age group; using HEC, using VAS to measure incidence and intensity of nausea, not measuring the acute nausea, using a standardized ginger extract is impractical and could affect the generalizability

Daily ginger is safe; some patient might experience an increase in gastrointestinal symptoms.

STUDY PURPOSE: To present the findings and conduct a critical appraisal of systematic reviews focusing on the effects of cannabinoids as a treatment for nausea and vomiting in patients with cancer during chemotherapy.

TYPE OF STUDY: Meta analysis and systematic review

DATABASES USED: EMBASE, PEDro, CINAHL, Cochrane Database of Systematic Reviews, LILACS, Medline, PsycINFO

YEARS INCLUDED: 2001 to 2015

INCLUSION CRITERIA: RCTs only, SRs focusing exclusively on cannabinoids for the treatment of CINV

EXCLUSION CRITERIA: Studies registered in PROSPERO and not completed or published by the date of search

TOTAL REFERENCES RETRIEVED: 2,206

EVALUATION METHOD AND COMMENTS ON LITERATURE USED: AMSTAR and PRISMA. Average AMSTAR score was 5, with low of 1 and high of 11. Max score of 11. Average PRISMA score was 13.2, ranging from 1 to 25. Max score of 27.

FINAL NUMBER STUDIES INCLUDED: 5 

TOTAL PATIENTS INCLUDED IN REVIEW: Not included 

KEY SAMPLE CHARACTERISTICS: Participants presenting nausea and/or vomiting attributed to any type of chemotherapy for cancer. Treatment included: THC, nabilone, dronabinol, and levonantradol compared to any pharmacologic or nonpharmacologic intervention.

PHASE OF CARE: Not specified or not applicable

Cannabinoids seem to be superior to placebo and equal to prochlorperazine in reducing nausea and vomiting, and, in general, are similar to standard antiemetics alone or in combination. Patient-reported outcomes indicated that patients tend to prefer cannabinoids over placebo and other antiemetics, but cannabinoids have a higher rate of adverse events when compared to traditional antiemetics.

Cannabinoids may be considered a therapeutic option for treating CINV. However, it is unclear from this analysis where cannabinoids are superior to traditional antiemetics in effectiveness or safety. There is a shortage of high-quality evidence to clarify these questions.

• Limited number of studies included
• Mostly low quality/high risk of bias studies

Cannabinoids may be effective and superior to placebo to treat CINV. Although adverse events were more frequent in patients treated with cannibinoids, patients preferred cannibinoids over other antiemetics. More studies are needed to evaluate the effectiveness and safety of cannabinoids in CINV.

• Studied the incidence of CINV in Japan, also evaluating risk factors and acute versus delayed CINV
• Assessed staff estimation of incidence of CINV

Patients were provided with seven-day diaries before the start of therapy with either highly emetogenic or moderately emetogenic chemotherapy. The patient must be receiving this type of therapy for the first time. Recording of digestive symptoms including severity of nausea, oral intake, and vomiting were measured using a visual analog scale. Investigators/colleagues recorded background information including date of birth, treatment history, use of anxiolytics, and use of opioids. Other risk factors including alcohol use, history of motion sickness or morning sickness, performance status, chemotherapy regimen, and clinical lab reports were collected in a case report, corresponding to the patient’s diary.

• N: 2,068 registered, 1,939 patients evaluated with case reports  
• AGE: 19-87 years, with a mean of 62 years
• MALES: 45.7%  
• FEMALES: 54.3%
• CURRENT TREATMENT: Chemotherapy, combination radiation and chemotherapy
• KEY DISEASE CHARACTERISTICS: Stage II, 20.6%; III, 24.2%; IV, 34.5%; PS-ECOG), 0, 70.8%; 1, 26.3%; 2, 2.5%; 3, 0.3%; 4, 0.1%. Cancer type: breast, hematologic, gynecologic, lung, gastric, colorectal, esophageal, HCC, other gastrointestinal. 
• OTHER KEY SAMPLE CHARACTERISTICS: Multiple types of chemotherapy

• SITE: Multi-site   
• SETTING TYPE: Multiple settings    
• LOCATION: Japan

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

This was a multicenter prospective cohort study, including university hospitals, cancer centers, and cancer treatment centers. One hundred eight institutions throughout Japan participated.

Diaries and visual analog scales have long been utilized in CINV research, although several other instruments are available and reliable. Descriptive statistics were used as were univariate analysis and multivariate analysis (Wald's test) to evaluate risk factors for both acute and delayed nausea, and acute and vomiting. Fisher’s exact test was used to measure differences of occurrence between risk factors and HEC, MEC types of chemotherapy. There was no mention how providers gauged emetogenic risk for the patients, so it was difficult to tell if this was using a reliable instrument.

Multiple cancers and multiple chemotherapy regimens were evaluated. Acute nausea and vomiting with HEC was 20.8% and 5.7%; with MEC, it was 6.7% and 1.7%, respectively. There was a high incidence of delayed nausea, 49.4% with HEC, and 41.7% with MEC. Delayed vomiting was low at 11.2% with HEC and 15.9% with MEC, which was notably higher; however, if the patient received a three-drug antiemetic regimen, it was then significantly lower. Motion sickness was associated with a higher risk for acute nausea, with men being more susceptible than women. A history of morning sickness was also a risk factor in women. HEC was associated with the highest risk in both genders. Prophylactic use of  three drug regimens was associated with reduced risk in men. Risk factor analysis also revealed that women were more susceptible to CINV in every aspect. Estimation of CINV by providers overestimated emetogenic risk.

A high compliance with guidelines was associated with a decreased incidence of CINV, particularly in the MEC group receiving three drugs. The authors recommend to study CINV for at least seven days. Mechanisms of acute CINV require further study to develop newer agents to target this symptom

• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Findings not generalizable
• Other limitations/explanation: Sample was too expansive with multiple disease states, all stages of disease and various chemotherapies. Inclusion criteria with previous treatments could be problematic. Lack of consistent chemotherapy regimens makes generalizing results difficult.

Implications for nurses indicates that knowledge and adherence to guidelines assist in managing CINV. As nurses, we must be advocates for patients, and ensure that the patient receives the best supportive care to prevent CINV and avoid breakthrough symptoms. Nurses should be aware of ONS guidelines to guide their practice.

To evaluate adherence to ASCO guidelines and to improve quality of antiemetic prescriptions.

An initial audit of 1,211 consecutive prescriptions for adult patients with solid tumors receiving outpatient chemotherapy were characterized based on consistency with ASCO guidelines.  

• Adherent to CINV prophylaxis
• Overadherent to guideline with addition of an additional antiemetic.  
• Nonadherent with two criteria identified: major deviation if the regimen had omitted an antiemetic either totally or in part, minor deviation if all appropriate medications utilized, but at lower than recommended dosing.

If a patient vomited, they were classified as having CINV if this occurred within five days after completion of chemotherapy and there was no other causation. Education was offered to clinicians regarding results of the audit. Review of the antiemetic policy was revised according to ASCO guidelines. A second audit occurred and included 201 patients.

• N: 1,211 prescriptions for antiemetics for adult patients with solid tumors between July and August 2015. This was repeated with another 201 prescriptions between September and October 2016.
• AGE: 18 to older than 60
• MALES: 49.5%  
• FEMALES: 50.5%
• CURRENT TREATMENT: Chemotherapy, combination radiation and chemotherapy
• KEY DISEASE CHARACTERISTICS: Head and neck cancer, 183 (15.1%); ovarian, 197 (16.3%); lung, 132 (10.9%); gall bladder, 128 (10.6%); rectum, 124 (10.3%); cervix, 100 (8.2%); stomach, 77 (6.3%); colon, 57 (4.7%); esophagus, 27 (2.2%); prostate, 25 (2.1%); urinary bladder, 17 (1.4%); sarcoma, 11 (0.9%); endometrium, 10 (0.8%); and other, 123 (10.2%)
• OTHER KEY SAMPLE CHARACTERISTICS: Antiemetic potential: High, 404 (33.4%); moderate, 586 (48.4%); low, 220 (18.2%); minimal, 1 (0.1%). Chemotherapy regimen: only chemotherapy, 1,005 (83%); single drug, 223 (35.4%); combination, 782 (64.6%). Chemotherapy: concurrent with radiation, 206 (17%); single drug, 183 (15.1%); combination, 23 (1.9%).

• SITE: Single site   
• SETTING TYPE: Outpatient    
• LOCATION: Tertiary Cancer Center in India

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

Retrospective study

Measuring incidence of vomiting, emergency visits, and hospitalizations using Descriptive statistics and Fisher exact test

Patient incidence of CINV with adherence to guidelines had a lower rate of vomiting, 6.6% versus 21.9% (p < 0.001), emergency visits, 2.6% versus 5.8%, p = 0.006 and hospitalization for emesis, 0.9% versus 4.9%, p < 0.001. In ASCO adherent guidelines, the proportion of prescriptions at initial audit was 63.6% and at reassessment was 98.5% (p < 0.001). Proportion of overuse was 41.3% at re-audit, and 68.3% before the intervention (p = 0.001). Post-audit intervention included education of providers regarding guideline and policy.

• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)

Use of guidelines enhances patient outcomes by significantly reducing the occurrence of CINV. Use of semi-rigid corrective actions lead to substantial improvement in adherence rates at this institution. This study demonstrates the importance of using guidelines in clinical care.

To assess the effects of Persumac, a Persian herbal preparation, on refractory CINV.

Patients were randomized to two study sequence groups. One group received Persumac first and then placebo in crossover. The other group received the opposite sequence. Patients were entered in the second course of chemotherapy. Crossover was done in the third course of chemotherapy. Persumac and placebo were taken three times daily before meals. A washout period of six days was done prior to the third chemotherapy course. Patients were studied for 33 days. Patients recorded information about the severity and number of nausea and vomiting episodes on a visual analog scale and answered questions related to frequency of forgetting to take the study drug or other antiemetics. All patients received standard triple antiemetic regimens. Persuma included sumac and Bunium persicum.

• N = 69   
• AGE: Median across groups = 47.5 and 46.8 years, range = 26-64
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: Breast cancer. All were receiving moderate or high emetic risk chemotherapy and had continued problems with CINV despite us of triple drug antiemetic regimens.

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

PHASE OF CARE: Active anti-tumor treatment

Double blind, randomized, crossover clinical trial

VAS for nausea and vomiting (1-10 scale)

Average nausea severity was significantly lower during the period when using the persumac (p < 0.001), with reduction in at least two points on the VAS in the delayed phase compared to baseline results. There was no significant effect for acute phase CINV. The number of vomiting episodes was reduced. There were very few patients who had complete response for CINV (range = 0%-23%)

Persumac appeared to have some benefit in reduction of the severity of delayed CINV in this study.

• Measurement/methods not well described
• Measurement validity/reliability questionable
• Subject withdrawals ≥ 10%  
• Other limitations/explanation: Timing of baseline measures not clear

Findings suggest that the Persian herbal medicine, Persumac, may have some benefit in reducing delayed CINV in women receiving moderate to severe emetic chemotherapy. Further evidence is needed to determine potential benefit.

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.