Chitapanarux, I., Tungkasamit, T., Petsuksiri, J., Kannarunimit, D., Katanyoo, K., Chakkabat, C., . . . Traisathit, P. (2018). Randomized control trial of benzydamine HCl versus sodium bicarbonate for prophylaxis of concurrent chemoradiation-induced oral mucositis. Supportive Care in Cancer, 26, 879–886.
To compare the efficacy of benzydamine HCl with sodium bicarbonate in the prevention of concurrent chemo rt-induced OM in patients with head and neck cancer.
Sixty locally advanced patients with head and neck cancer treated with high-dose RT concurrently with platinum-based chemotherapy were randomly assigned to receive either benzydamine HCl or sodium bicarbonate from the first day of treatment to two weeks after completion of treatment.
RCT with two intervention groups
Patients were evaluated by the radiation oncologists at baseline before CCRT, weekly during CCRT, at the end of CCRT, and at four weeks after CCRT. The Oral Mucositis Assessment Scale (OMAS) was used to assess severity of mucositis. Ulceration score was 0 for no lesion, 1 for lesion less than 1 cm2, 2 for lesion 1–3 cm2, and 3 for lesion more than 3 cm2. Erythema score was 0 for no lesion, 1 for mild to moderate erythema, and 3 for severe erythema. Pain score (0–10), all prescribed medications including analgesic, artificial saliva supplement, and anti-infection medications, the need for hospitalization, treatment interruption, and the addition of nutritional support or feeding tube were also recorded. Oral candidiasis assessment was based on the physical examination of pseudomembranous lesions or angular cheilitis in centers except at CMUH center where confirmation by microscopic identification of Candida was used.
Prophylaxis rinsing with benzydamine HCl can be more effective in reducing severity of OM induced by CCRT, when compared to basic care with sodium bicarbonate mouthwash. Median of OMAS scores at weekly assessment during CCRT was lower in benzydamine HCl group compared to control. In both groups, maximum of third quartile of OMAS scores around fifth to seventh week of CCRT. Scores decreased at four weeks after CCRT. Statistically, median for OMAS scores was significantly lower in study group at every week between second and eighth week of CCRT. The corresponding p values for those weeks in chronological order were 0.003, < 0.001, < 0.001, < 0.001, < 0.001, 0.01, and 0.04. Maximum of third quartile of OMAS scores to be around fifth to sixth week in both groups. Maximum OMAS score across whole period of CCRT in benzydamine HCl group was 25, lower than maximum of 37 in sodium bicarbonate group. No significant difference in median of pain scores between two groups during CCRT and at follow-up. Corresponding p values from second to eighth week were 0.88, 0.59, 0.96, 0.73, 0.63, 0.92, and 0.15 and p value at follow-up after CCRT was 0.8. Maximum of third quartile of pain scores at seventh week of CCRT in study group and eighth week in control group. Maximum pain score across period of CCRT was 10 in both groups. Four weeks after CCRT, median of pain score decreased to 2 in both groups. Poor compliance was defined as patients in postoperative CCRT group and in definitive CCRT group who received weekly chemotherapy less than 3 cycles and 4 cycles, respectively. More patients with poor compliance in control group than in study group (i.e., 13 patients versus 10 patients). No differences were found between the two groups. Most patients in both groups need analgesic drugs; 89% in control group and 90% in study group, p value = 1. The most common analgesic drugs used were opioids (syrup morphine/morphine sulfate tablet; MST/morphine sulfate sustain released; kapanol®), prescribed usage rates were 48% in control group and 33% in study group. For antifungal agents, none in benzydamine HCl group needed them, whereas 19% of patients in sodium bicarbonate group required nystatin oral suspension or clotrimazole tablet. Rate of feeding tube placement was same in both groups during CCRT (i.e., 24 and 22% in the study group and the control group, respectively). Oral retention and compliance for mouthwash products were better in sodium bicarbonate arm than in benzydamine HCl arm. Four patients (6.75%) in study arm could not tolerate full dose of benzydamine HCl due to burning and stinging sensation. For these patients, mouthwash was diluted at 1:1 with water.
Prophylaxis oral rinsing with benzydamine HCl for patients undergoing high-dose radiotherapy concurrently with platinum-based chemotherapy was superior to sodium bicarbonate mouthwash in terms of alleviating the severity of oral mucositis and encouraging trend for reducing the need of oral antifungal agents use.
Review prophylaxis and acute treatment protocol practices.
Weissheimer, C., Curra, M., Gregianin, L.J., Daudt, L.E., Wagner, V.P., Martins, M.A.T., & Martins, M.D. (2017). New photobiomodulation protocol prevents oral mucositis in hematopoietic stem cell transplantation recipients--A retrospective study. Lasers in Medical Science, 32, 2013–2021.
The aim of this study was to evaluate the effect of photobiomodulation (PBM) in reducing the incidence and severity of OM in patients undergoing HSCT, comparing two protocols that differ only in session frequency, either daily or three times a week.
PBM applied three times per week versus seven times per week in patients undergoing HSCT
A retrospective study was to evaluate the preventive effect of PBM applied three times per week versus seven times per week in patients undergoing HSCT.
Differences between groups were evaluated using the chi-square test or Fischer’s exact test for qualitative data and the Mann-Whitney test for quantitative data. Receiver operating characteristic (ROC) curves were constructed to analyze the sensitivity and specificity of quantitative risk factors in predicting the presence or absence of OM. The area under the curve is a measure of test accuracy. The SPSS for Windows software package, version 18.0, was used to perform these statistical analyses. Two-way analysis of variance (ANOVA) was used to compare OM average between groups, and the t test was used to compare the average OM at each point.
PBM was effective in preventing OM in patients undergoing HSCT even when it was applied three times a week. Both PBM protocols were equally efficient in preventing OM (p = 0.34, ANOVA).
Independent of the PBM protocol used, patients who received allogeneic transplant (p < 0.01, Fischer’s exact test), total body irradiation (TBI, 12 Gy) (p = 0.01, chi-square test), busulfan plus cyclophosphamide (p < 0.01, chi-square test), or methotrexate-containing regimens (p < 0.01, Fischer’s exact test) demonstrated higher OM incidence and severity. Myelosuppression (p < 0.01, Mann-Whitney test) and impaired renal function (p = 0.02, Mann-Whitney test) were also considered risk factors for OM.
The study indicates that PBM is effective in preventing OM in patients undergoing HSCT even when administered three times a week.
OM is frequently seen side effect of patients receiving HSCT, these lesions impact patient quality of life, controlling this condition is extremely important, and developing effective interventions is a high priority in protocol support among patients with cancer.
Cabrera-Jaime, S., Martinez, C., Ferro-Garcia, T., Giner-Boya, P., Icart-Isern, T., Estrada-Masllorens, J.M., & Fernandez-Ortega, P. (2018). Efficacy of Plantago major, chlorhexidine 0.12% and sodium bicarbonate 5% solution in the treatment of oral mucositis in cancer patients with solid tumour: A feasibility randomised triple-blind phase III clinical trial. European Journal of Oncology Nursing, 32, 40–47.
To evaluate/compare three treatments for oral mucositis: (1) Plantago major extract mouthwash, (2) chlorhexidine 0.12%, and (3) aqueous solution of 5% sodium bicarbonate for the treatment of oral mucositis in patients with solid tumors. Evaluation points included healing time, pain, oral intake, and quality of life.
Randomized controlled trial (phase 3)
The treatment was 14 days for all groups. All groups received education regarding the management of mucositis, a set of instructions, a diary to record signs and symptoms of mucositis, and instruction for proper storing of the mouthwashes. All participants were instructed to rinse with 8 ml of solution for two minutes every six hours. They were instructed to leave 15 minutes between the two mouthwashes.
Randomized controlled trial; investigators, participants, care providers, and statistician were all blinded.
In this small group, there is no advantage in using a chlorhexidine or Plantago major extract mouthwash in comparison to a double sodium bicarbonate solution. The latter is likely less expensive and more readily available
This study does not support the use of Plantago major or chlorhexidine mouthwashes over double doses of sodium bicarbonate 5% aqueous solution.
Aghamohammadi, A., Moslemi, D., Akbari, J., Ghasemi, A., Azadbakht, M., Asgharpour, A., & Hosseinimehr, S.J. (2018). The effectiveness of Zataria extract mouthwash for the management of radiation-induced oral mucositis in patients: A randomized placebo-controlled double-blind study. Clinical Oral Investigations, 22, 2263–2272.
Primary: To evaluate the use of Zataria multiflora (ZM) extract mouthwash to reduce the incidence and severity of oral mucositis (OM) in adult patients with head and neck cancer undergoing radiation therapy alone or combined radiation and chemotherapy.
Secondary: The impact of ZM extract mouthwash on the amount of opioid used, the use of anti-inflammatory drug use, antibiotic use, and body weight over the course of therapy
Double blinded, randomized, placebo controlled study
Primary outcomes:
Secondary outcomes:
The use of ZM mouthwash positively impacted the incidence and severity of OM in patients with head and neck cancer undergoing head and neck radiation with or without concurrent chemotherapy. In addition, the ZM mouthwash contributed to less use of opioid analgesia, less antibiotic use, and decreased weight loss.
ZM may offer an option for decreasing OM in patients undergoing radiation with or without concurrent chemotherapy in the head and neck cancer population.
Ramirez-Amador, V., Anaya-Saavedra, G., Labardini-Mendez, J., & Ponce de Leon-Rosales, S. (2018). Double-blind placebo-controlled randomized clinical trial evaluating doxycycline effects on chemotherapy-induced oral mucositis. Journal of Clinical Pharmacy and Therapeutics, 43, 202–208.
PURPOSE: To use sub-antimicrobial doxycycline 50 mg per day on patients with leukemia to reduce the onset and severity of OM
TYPES OF PATIENTS ADDRESSED: Patients with ML or LL
RESOURCE TYPE: Evidence-based guideline
PROCESS OF DEVELOPMENT: Patients aged 15 years and older with specific leukemia (N = 47). Patients had basic oral examination and were taught oral care protocol. A baseline oral examination was done three times per week for three weeks. The strategy of development was to prevent the devastating consequences of OM in patients with leukemia.
INCLUSION CRITERIA: Aged 15 years or older, male or female
EXCLUSION CRITERIA: Patients using the following medications: acitretin, isotretinoin, or tretinin
The low-dose use of doxycycline proved ineffective in the management of OM in patients with acute leukemia during chemotherapy.
Effectiveness unlikely. The intervention with doxycycline lacks effectiveness in the reduction of the severity or onset of OM in patients with leukemia.
The findings are not generalizable; limited to one disease group.
The nursing implication is that continued attention to OM is needed to manage and treat the dose interruption and debilitating nutritional problems associated in patients receiving treatment for cancer.
Rugo, H.S., Seneviratne, L., Beck, J.T., Glaspy, J.A., Peguero, J.A., Pluard, T.J., . . . Litton, J.K. (2017). Prevention of everolimus-related stomatitis in women with hormone receptor-positive, HER2-negative metastatic breast cancer using dexamethasone mouthwash (SWISH): A single-arm, phase 2 trial. Lancet Oncology, 18, 654–662.
PURPOSE: Prevention of combination drug therapy-induced OM (stomatitis) This is the second clinical trial supported by Novartis in patients taking combination drug therapy (everolimus and exemestane).
TYPES OF PATIENTS ADDRESSED: Patients with hormone receptor-positive, HER2-negative metastatic breast cancer
RESOURCE TYPE: Evidence-based guideline
DATABASES USED: PubMed
INCLUSION CRITERIA: Metastatic breast cancer with hormone receptor-positive, HER2-negative
EXCLUSION CRITERIA: All other types of cancer
PHASE OF CARE: Late effects and survivorship
This is the second clinical trial performed by Novartis to eliminate dose interruption of everolimus tablets in combination therapy for women with hormone receptor-positive, HER2-negative metastatic breast cancer. Twenty-three investigational sites based in the United States participated. The average age of the 92/86 female participants was 61 years. It was a single-arm phase 2 study. The primary endpoint was the incidence of grade 2 or worse OM was significantly reduced by proactive oral care use of alcohol-free dexamethasone oral solution (SWISH).
This is the first and largest OM prevention study completed that combines therapeutic management with proactive patient engagement to reduce the incidence of OM in patients who are postmenopausal and receiving combination pill therapy(everolimus and exemestane) as treatment for hormone receptor-positive, HER2-negative metastatic breast cancer. The use of dexamethasone oral solution for two minutes, four times a day, will stop OM from occurring or reduce the severity. It is used for eight weeks or longer if results are positive.
The primary limitation is it is for only one targeted group and for one target drug. The clinical trial is high strength and high quality. There could not be a control group due to the fact that the investigators did not find it ethical for patients to suffer with OM. Novartis is the manufacture of dexamethasone oral rinse and gives free eight-week supplies.
The nursing implication is to teach an oral care protocol to all patients with cancer and ask for more clinical trials for patients with other types of cancer or receiving other treatments. The SWISH trial found that a commercially available, inexpensive, well tolerated dexamethasone oral rinse is an effective intervention in the prevention of OM in women with HER2-negative metastatic breast cancer treated with everolimus.
Gallagher, L.M., Lagman, R., & Rybicki, L. (2018). Outcomes of music therapy interventions on symptom management in palliative medicine patients. American Journal of Hospice and Palliative Care, 35, 250–257.
Data was collected on admitted palliative medicine patients receiving music therapy from September 2000 to May 2012. A board-certified music therapist (MT-BC) on the unit conducted music therapy sessions with individual palliative medicine patients and family members present. Multiple goals may have been addressed at a single session, using a variety of live patient-preferred musical interventions. Interventions included six main categories—music listening, verbal/cognitive participation, vocal participation, physical participation, verbal/emotional participation, and music-assisted relaxation. Symptom evaluations from patients included pre- and post-session severity of pain, depression, anxiety and shortness of breath. Data collected on patients included standardized music therapy assessment, elements of standardized music therapy, clinical note, patient related information, patient goals for the session, interventions used by the music therapist, symptom evaluations from patients, behavioral evaluations from the therapist, music used, patient and family member reactions, and narratives.
This is a retrospective study of data collected on palliative medicine patients admitted from September 2000 to May 2012 who participated in music therapy sessions.
Statistically significant reduction improvement in pre- and post-session mean scores were reported for all measurements (p < 0.001) except body movement (p = 0.16). However, the percentage of patients who achieved the clinical significant threshold ranged from 0.7% to 66.2%. Outcomes with the highest percentage of patients with clinically relevant improvement were mood (66.2%), vocalization (58.7%), and facial expression (55.6%). Only 12.3% of patients experienced any clinically relevant improvement. 96% of participants had an overall positive verbal response to the session versus 4% of participants that experienced an ambivalent or no verbal response. Patients who listed pain, depression, anxiety, shortness of breath, or mood as a goal for music therapy achieved the most improvement in these symptoms. Vocalization seemed to have significantly improved when verbal/emotional intervention was used and when distraction was a goal of music therapy. There was no impact on patient demographic or cancer diagnosis on outcomes.
Music therapy does appear to have a positive effect on symptoms of dyspnea and should be considered as an adjunct to current standard interventions. However, more research is needed to determine the degree of clinical benefit of music therapy in the improvement of dyspnea, as well as its cost-effectiveness and duration effect.
Music therapy should be considered as an adjunct to current standard interventions for dyspnea.
Simon, S.T., Kloke, M., Alt-Epping, B., Gartner, J., Hellmich, M., Hein, R., . . . Voltz, R. (2016). EffenDys-fentanyl buccal tablet for the relief of episodic breathlessness in patients with advanced cancer: A multicenter, open-label, randomized, morphine-controlled, crossover, phase II trial. Journal of Pain and Symptom Management, 52, 617–625.
To determine time to onset, efficacy, feasibility, and safety of transmucosal fentanyl (FBT) in comparison to immediate-release morphine (IRM) for the relief of episodic breathlessness.
Fentanyl buccal tablets 100 mcg and 2% immediate release morphine are titrated to 1/6th dosing based on their daily oral morphine equivalent (DOME) to start and increase up to 400 mcg fentanyl or 1/6th + 100% of DOME. Patients were to keep a diary of when dyspnea episode started and when medication taken, with various times to record effectiveness and oxygen saturation over one hour. Patients had twice-a-day safety checks by researchers. Actual doses used were 100-200 mcg of fentanyl and 6-36 mg morphine. Patients crossed over after five days (of a 10-day study).
This is an open-label, randomized, active-controlled (morphine), crossover, phase II trial with an open label dose titration phase.
Oxygen saturation testing was done, stop watch, and a breathlessness scale of 0-10, with 10 being the worst score. Respiratory rate, Glasgow Coma Scale, and Karnofsky level.
The Breathlessness Index Difference (BID) was calculated. At 10 minutes, the difference was p = 0.051, with mean time to onset of meaningful breathlessness relief was for FBT 12.7 minutes (plus or minus 10 minutes), and, for IRM, 23.6 minutes (plus or minus 15.1 minutes), with a mean difference of 10.9 minutes (95% CI [-24.5, 2.7], p = 0.094) in favor for FBT (FBT-IRM). Time of onset between morphine and fentanyl was a mean difference of 8.4 (95% CI [-18.8, 2.1], p = 0.085), which was not statistically significant.
Fentanyl was found to work quicker then MS, without any difference in side effects or satisfaction with the medications.
For many patients, once SOB has started, time to relief can be an important factor in keeping the anxiety factor down. For some, the price of fentanyl outweighs the benefit against morphine as both have tolerated side effects for opiate-tolerant patients.
Hui, D., Kilgore, K., Frisbee-Hume, S., Park, M., Liu, D., Balachandran, D.D., & Bruera, E. (2017). Effect of prophylactic fentanyl buccal tablet on episodic exertional dyspnea: A pilot double-blind randomized controlled trial. Journal of Pain and Symptom Management, 54, 798–805.
To study the effect of fentanyl in preventing dyspnea before exertion.
Opiate-tolerant patients were given a six-minute walk test for baseline, then later given fentanyl or a placebo, waited 30 minutes, then repeated the six-minute walk test. Study measures were then taken between the two arms.
Double blind randomized placebo controlled trial comparing baseline six-minute walk test and then a second six-minute walk test (6MWT) effects of placebo versus single dose of fentanyl buccal tablet 30 minutes prior to second walk.
Dyspnea was measured using a modified BORG scale from 0-10, with 10 indicating the worst score. Vital signs of BP: O2 saturation, heart rate, respiratory rate taken before and after the six-minute walk test. Distance walked per minute was recorded. Lung function was only done at baseline. Neurocognitive testing was done before medication and after the second six-minute walk.
No difference with either arm seen for distance walked or fatigue, or vital signs other then respiratory rate between the first and second 6MWTs (mean change = 2.6, 95% CI [0.4, 4.7]) with a trend toward greater level of dyspnea relief compared with placebo (estimate = 0.25, p = 0.068).
Buccal fentanyl had a significant effect in reducing dyspnea then placebo after 30 minutes, when patients exerted themselves.
Nurses caring for patients with dyspnea recognize the need to provide interventions that minimize dyspnea during daily activities, particularly when dyspnea interferes with ADLs and impacts patients' quality of life. Interventions such as prophylactic FBT may enable patients to participate in activities, regain independence, and improve their quality of life without experiencing adverse events such as dizziness, drowsiness, and nausea.
Kako, J., Morita, T., Yamaguchi, T., Kobayashi, M., Sekimoto, A., Kinoshita, H., ... Matsushima, E. (2018). Fan therapy is effective in relieving dyspnea in patients with terminally ill cancer: A parallel-arm, randomized controlled trial. Journal of Pain and Symptom Management, 56, 493–500.
To determine the effect of fan therapy on dyspnea in patients with terminally ill cancer.
Fan therapy consisted of directing a fan to blow air for five minutes across the region innervated by the second/third trigeminal nerve branches. Control was directing a fan to blow air for five minutes to legs. Intervention delivered after a washout period for opioids.
Randomized controlled trial
ESAS-r (ESAS-revised): used NRS for dyspnea (0-10 scale) (primary measure), facial temperature, respiratory rate, peripheral O2 saturation, and heart rate (secondary measures)
Improvement in dyspnea for the treatment arm was seen with mean NRS scores that changed by -1.35 in the treatment arm versus a change of -0.1 in the control arm (p < 0.001) and the number of patients who experienced a greater than one or two-point reduction on their NRS was greater (80%) when compared to the control group (25%). There was also a reduction noted in drowsiness in the treatment group. Significant secondary outcomes included that the mean change in drowsiness on NRS was 0.4 for the treatment group versus -0.45 for control (p = 0.01) and facial temperature was significantly lower after the intervention for the treatment group (reduction of 1.43 degrees C) versus control (reduction of 0.01) (p = 0.003)
The authors conclude that the study presents evidence that fan therapy is effective for the treatment of dyspnea in terminally ill patients with cancer.
This study has significant implications for nursing as it provides an intervention for dyspnea that could be wholly within the ability of nurses to deliver and could be taught to families. It is also an intervention with little risk and could offer patients some control.