Ersoy, M.A., Noyan, A.M., & Elbi, H. (2008). An open-label long-term naturalistic study of mirtazapine treatment for depression in cancer patients. Clinical Drug Investigation, 28, 113–120.
To evaluate the risk-benefit profile of the use of mirtazapine for the treatment of depression in patients with cancer
Patients were enrolled who presented for psychiatric evaluation and treatment of depression and met DSM-IV criteria for major depression (HAM-D-17 score > 18). Patients started a drug therapy of mirtazapine, 15 mg/day day orally; the dose was increased to 30 mg/day in the fourth week of therapy if patients were not responding and had no adverse effects. All patients continued receiving the minimum dose for 24 weeks, but the use of other medications was not controlled. Patients were assessed at the initial visit and at the end of weeks 4, 12, and 24. Adverse effects were noted during routine assessments.
Active treatment
Open-label (no blinding) longitudinal study
Clinical efficacy was defined as a greater than 50% reduction in HAM-D-17 scores (defined as a positive treatment response). Patients with HAM-D-17 scores of 8–18 were defined as partial responders. Patients with HAM-D-17 scores less than 8 and a period of at least two months without significant symptoms of depression met the criteria for remission. All patients obtained at least a 50% reduction in HAM-D-17 scores, which improved from baseline to one month and were maintained for the duration of the study (24 weeks) (p < 0.001). HAM-D-17 scores significantly decreased from baseline to one month (p < 0.001). The drug was well tolerated, and no one required discontinuation of therapy. Minimal adverse effects were reported, including mild to moderate hand tremor, fatigue, weight gain, and restless leg syndrome.
The study provides preliminary evidence that (open-label) the drug mirtazapine is safe, efficacious, and tolerated.
This particular agent may have antiemetic effects, which may be desirable in this patient population, and it had a minimal side-effect profile. Future research should include a randomized, controlled trial examining mirtazapine versus selective serotonin reuptake inhibitors in this patient population.
Ernst, E., & Pittler, M.H. (2000). Efficacy of ginger for nausea and vomiting: A systematic review of randomized clinical trials. British Journal of Anaesthesia, 84, 367-71.
The review identified three studies on postoperative nausea, one for seasickness, one for morning sickness, and one for chemotherapy-induced nausea and vomiting (CINV). Studies were performed in the United States and in Denmark.
The total number of participants in the studies was 288 for postoperative nausea, 30 for morning sickness, 80 for seasickness, and 41 for CINV.
Clinical data was insufficient to draw a firm conclusion on the benefits of ginger for nausea and vomiting.
Although no adverse events were reported in these studies, ginger may have an adverse effect. A German monograph reported that ginger may be mutagenic in pregnancy.
Ergun, M., Eyigor, S., Karaca, B., Kisim, A., & Uslu, R. (2013). Effects of exercise on angiogenesis and apoptosis-related molecules, quality of life, fatigue and depression in breast cancer patients. European Journal of Cancer Care, 22, 626–637.
Evaluate moderate intensity exercise programs for patients with breast cancer and their effect on several immune indicators as well as on fatigue, depression, and quality of life
Lab was obtained at week 0 and 12 and analyzed. Quality of life, fatigue, and depression were evaluated before and after the exercise program using tools mentioned. Patients were assigned to one of three groups. All were provided education. Group one did supervised exercise consisting of 45 minutes per day three times per week and brisk walking for 30 minutes per day three times per week. Group two did brisk walking for 30 minutes per day three times per week. Group three received education only. Patients wrote down their progress, and groups two and three were interviewed over the phone once a week. Arm circumference was measured to control for lymphedema at zero, one, two, and three months.
PHASE OF CARE: Transition phase after active treatment
Prospective, randomized controlled study
Demographics were similar among the three groups. Exercise groups had a statistically significant decrease in some of the biomarkers, while the education group had a statistically significant increase in monocyte chemoattractant protein 1 levels. Functional score and global health score in both exercise groups increased. Depression score was reduced in the supervised exercise group (p < .05). However, no significant differences were seen between groups after the intervention.
Significant changes in biomarkers were found at the end of 12 weeks, and improvements were seen in quality of life and depression in the supervised and unsupervised exercise groups.
Nurses encouraging patients with breast cancer to stay physically active and adopt a moderate exercise program is important to improve quality of life and help with symptoms of depression.
Erdem, O., & Gungormus, Z. (2014). The effect of royal jelly on oral mucositis in patients undergoing radiotherapy and chemotherapy. Holistic Nursing Practice, 28, 242–246.
To determine the efficacy of royal jelly on oral mucositis in patients receiving chemotherapy and radiation
Patients were divided into two groups. All patients received benzydamine hydrochloride and nystatin rinses. In the experimental group, royal jelly was swished orally for 30 seconds and then swallowed twice per day for a total of 1 g per day. Patients could not eat or drink within 30 minutes of using the royal jelly. Both groups used the mouthwash protocol or mouthwash protocol plus royal jelly until mucositis was resolved. All participants and assessors were blinded to group. Oral mucosa was divided into five sites—labial mucosa, buccal mucosa, gingivae, tongue, and soft and hard palates—and the mucositis score was determined daily by a trained researcher for each site until no further evidence of mucositis existed.
No statistical difference was seen in mucositis severity at the beginning of the study between the two groups. For grade 1 mucositis, the mean number of days to healing in the royal jelly group was 1.1 days, and in the control group it was 2.7 days (U = 64; p = 0.0001). For grade 2 mucositis, the mean number of days to healing in the control group was 5.8 days, and in the experimental group it was 3 days (U = 77; p = 0.0001). For grade 3 mucositis, those in the experimental group had a faster healing time than those in the control group (U = 59; p = 0.005).
The addition of royal jelly to a mouthwash protocol with benzydamine and nystatin rinses significantly decreased the healing time for grade 1, 2, and 3 oral mucositis.
Royal jelly should be considered as an additional intervention to promote the healing of oral mucositis caused by chemotherapy and radiation. Royal jelly, in addition to a mouthwash protocol consisting of a benzydamine and nystatin rinse, effectively reduced the number of days to complete healing of oral mucositis. The sample in this study included a wide variety of cancer types as well as a wide range of types of chemotherapy and number of chemotherapy cycles.
Ercoli, L.M., Castellon, S.A., Hunter, A.M., Kwan, L., Kahn-Mills, B.A., Cernin, P.A., . . . Ganz, P.A. (2013). Assessment of the feasibility of a rehabilitation intervention program for breast cancer survivors with cognitive complaints. Brain Imaging and Behavior, 7, 543–553.
To evaluate the feasibility of a cognitive rehabilitation intervention for persistent post-treatment cognitive issues in survivors of breast cancer and to conduct a substudy to garner preliminary data related to the use of quantitative electroencephalography (qEEG) to assess changes in cognitive function
Five weekly, manualized, two-hour sessions were provided to five cohorts of four to nine participants. The last cohort participated in the qEEG substudy. Two difficulty levels of in-class cognitive training and three levels of homework exercises were designed to build skills in the targeted areas of attention, executive function, and memory. Participants were encouraged to do four 20-minute sessions of homework exercises per week and log their time. Participants received a training manual workbook, CDs for auditory exercises, answer keys, and a stopwatch. In-class education focused on a specified targeted area and instructions on coping strategies to minimize anxiety (such as deep breathing, relaxation, pacing, and countering negative thoughts). Goal attainment was discussed during the group sessions to facilitate setting individual short-term and long-term goals. Neurocognitive testing, self-report instruments, and the qEEG (substudy) were administered at baseline (T0), within one week (T1), and at two (T2), and four (T3) months after completing the intervention.
Prospective trial
PAOFI totals and memory complaint scores decreased between T0 and T1 (p = .031 and p = .009, respectively) and were maintained at T3 (p < .0001 in both). Decreases in high-level cognitive functions (PAOFI scale) were demonstrated at T3 (p = .005). Significant short- and long-term improvements were observed for the symbol digit, Stroop reaction time, and trail A tests (p < .05). Meaningful improvement by a reliable change index (RCI) occurred for 19% of patients (n = 5) between T0 and T1, and 30% of patients (n = 8) by T3. RCI improvement (in ≥ 2 of 16 tests) predominantly occurred for verbal learning and memory (HVLT-R), processing speed (symbol digit), and divided attention (shifting attention test). Absolute alpha power increase (qEEG) was associated with PAOFI improvements at T1 (p = .014). Change in alpha power correlated with change in PAOFI memory subscale at T1 (p = .021) and T2 (p = .004). Correlation also was noted with the PAOFI HLC subscale at T2 (p = .030) and T3 (p = .048).
This study's results demonstrated the feasibility of this cognitive rehabilitation intervention and preliminary evidence for the improvement of subjective and objective cognitive function. Larger randomized, controlled trials are necessary to further determine efficacy. Preliminary results supported the potential use of qEEG as a measure of change in cognitive function. An additional randomized, controlled trial is underway.
Cognitive rehabilitation interventions appear to be promising. Nurses should maintain an awareness of research results in this area and consider suggesting appropriate clinical trials to eligible survivors.
Epstein, D. R., & Dirksen, S. R. (2007). Randomized trial of a cognitive-behavioral intervention for insomnia in breast cancer survivors. Oncology Nursing Forum, 34, E51–E59.
To determine the efficacy of a cognitive-behavioral intervention for treating insomnia in survivors of breast cancer.
Participants were assigned to either a multicomponent intervention with stimulus control, sleep restriction, and sleep education and hygiene or a control intervention with sleep education and hygiene. Participants attended four weekly treatment group sessions (the first session was two hours and the other three were one hour) followed by two weekly 15- to 30-minute individual telephone sessions. Outcomes measures were sleep-onset latency, wake-after-sleep onset, total sleep time, time in bed, sleep efficiency, and sleep quality.
The study was conducted in university and medical center classrooms.
Patients were undergoing the follow-up phase of care.
This was a randomized, controlled trial.
After the intervention, based on daily sleep diaries, both groups improved in sleep-onset latency, wake-after-sleep onset, total sleep time, time in bed, sleep efficiency, and sleep quality. A between-group difference existed for time in bed. Wrist actigraph data showed significant pre- to postintervention changes for sleep-onset latency, wake-after-sleep onset, total sleep time, and time in bed. When compared to the control group, the multicomponent intervention group rated overall sleep as more improved.
A nonpharmacologic intervention is effective in the treatment of insomnia in survivors of breast cancer.
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.
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.
The study was conducted at 16 centers in North America (15 in the United States and 1 in Canada).
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.
Benzydamine was not effective in reducing more severe mucositis in patients receiving high, single, daily RT regimens of 220 cGy per day or more.
Epstein, J.B., Epstein, J.D., Epstein, M.S., Oien, H., & Truelove, E.L. (2008). Doxepin rinse for management of mucositis pain in patients with cancer: One week follow-up of topical therapy. Special Care in Dentistry, 28(2), 73–77.
To determine the impact of repeated dosing with doxepin rinse over the course of one week in patients with oral mucositis
Patients were instructed to rinse the oral cavity for 1 minute with 5 mL doxepin suspension (5 mg/mL) and then spit it out. Patients were to continue using the rinse as needed, 3–6 times per day, for the following week until their second visit and assessment. Standard of care for mucositis also was used during this time. Subjects used diaries to record analgesic use and mouth rinses.
The study was conducted at a single site, outpatient setting in Canada.
This was a nonrandomized, unblinded, uncontrolled, open-label study.
Statistically significant reductions in pain scores were reported for two hours following doxepin rinse during the initial visit (p < 0.05). Patients recalled that their pain significantly dropped within 5 minutes of rinsing over the week of repeated dosing (p < 0.05). At the follow-up visits, subjects reported statistically significant pain reduction 5 minutes after doxepin rinsing (p < 0.05). No changes were reported in systemic analgesics used during the study week despite the increasing severity of mucositis. No significant differences were found in mucositis scores over time.
Doxepin rinsing in addition to usual oral care produced reduced intensity of pain levels but no apparent difference in mucositis severity. No firm conclusions can be drawn from this extremely small sample.
The doxepin rinse was well tolerated, and the results warrant a larger, randomized, controlled clinical trial.
Epstein, A.S., Hartridge-Lambert, S.K., Ramaker, J.S., Voigt, L.P., & Portlock, C.S. (2011). Humidified high-flow nasal oxygen utilization in patients with cancer at Memorial Sloan-Kettering Cancer Center. Journal of Palliative Medicine, 14, 835–839.
To understand the prevalence of humidified high-flow nasal oxygen (HHFNOx) use at the authors’ institution, and to investigate characteristics related to HHFNOx initiation, discontinuation, and consistency with patient goals of care
In this retrospective study, the characteristics of HHFNOx—Optiflow™—use, including malignancy diagnosis, underlying cardiopulmonary disease, reason for HHFNOx initiation (hypoxia/dyspnea), duration of HHFNOx therapy, reported HHFNOx impact, reason for discontinuation (stable, declined, or expired), and patient outcome were analyzed (discharge/code status). Patients who used the HHFNOx device—Optiflow™—since 2008 were identified via the institution’s database search. Of the 353 patients identified, 183 were randomly selected for analysis. Objective (documented patient comfort and SaO2 on the device, and “step up” and “step down” grading to other oxygen support devices) and subjective (recorded patient and clinician impressions of tolerability) outcomes, oxygen saturation (SaO2), and oxygen interventions pre and post HHFNOx were examined.
HHFNOx was effective in the stabilization or improvement of oxygen saturation in the majority of treated patients. Though HHFNOx devices are expensive, they are a more cost-effective oxygen delivery alternative because they may help prevent escalation to more invasive oxygenation (e.g., mechanical ventilation).
HHFNOx seems well tolerated by various malignancies and clinical trajectories and generally safe. The study claims to be the only clinical description of HHFNOx device used exclusively in the cancer population. Users were able to benefit from high flow of oxygen delivery while still being able to eat and drink (as opposed to oxygen delivery via face mask or face tent).
Enomoto, T.M., Johnson, T., Peterson, N., Homer, L., Walts, D., & Johnson, N. (2005). Combination glutathione and anthocyanins as an alternative for skin care during externalbeam radiation. American Journal of Surgery, 189, 627–631.
To evaluate if the topical application RayGel (contains glutathione and anthocyanin) decreases radiation dermatitis
Both groups received instruction in standard skin care and used aloe vera gel and vitamin E after treatment. Gel or placebo was applied to breasts one to three hours prior to radiation therapy. The placebo was a water-based gel.
The study used a prospective, placebo-controlled design.
Whole breast severity scores were lower with RayGel at 93.7% versus the placebo at 123%. The difference in the worst site score was not as pronounced; however, the RayGel Group was 14% less than that of the placebo group, at 39.2% and 45.5%, respectively. None of the findings were significant.
RayGel tended to be superior to the placebo, although significance could not be determined because of the small sample size.