Ben-David, M.A., Elkayam, R., Gelernter, I., & Pfeffer, R.M. (2016). Melatonin for prevention of breast radiation dermatitis: A phase II, prospective, double-blind randomized trial. The Israel Medical Association Journal, 18, 188–192. Retrieved from https://www.ima.org.il/filesupload/imaj/0/193/96915.pdf
To evaluate a cream containing melatonin in terms of efficacy in reducing acute radiation dermatitis during and immediately after radiation therapy, and to examine patient-reported comfort during the study period
PHASE OF CARE: Active antitumor treatment
Phase II, prospective, double-blind, randomized
The researchers reported no significant difference in skin toxicity for both groups for the first four weeks of radiation treatment. The authors reported findings of significance in terms of reduced radiation dermatitis in the melatonin group at week five to seven (p = 0.049). After radiation was complete, the authors reported significant findings at the two-week follow-up visit in terms of reduced dermatitis in the melatonin group (p = 0.03). The researchers found no difference in the melatonin group and placebo group patient questionnaire reports of symptoms during treatment (including pain, burning, itching). Other analysis showed that women in the melatonin group who were older and smoked showed less radiation dermatitis (significance values p = 0.021 and p = 0.007). Four patients in the melatonin group sustained an allergic reaction limited to the treated skin, which required treatment with a topical and/or oral steroid.
Women with early stage breast cancer (stage 0–II) who are status postlumpectomy and undergoing daily radiation treatment for five weeks may experience reduced skin toxicity from the twice daily application of a melatonin containing cream to the treatment area.
As there is currently no consensus or evidence-based practice to follow for the treatment for radiation dermatitis, this study could be used to identify a treatment option and possibly specific product use in other institutions where radiation is delivered. Although this study was limited to women with breast cancer who had undergone lumpectomy, there could be utility in applying the melatonin cream to patients undergoing radiation therapy for other types of cancers (e.g., head and neck cancer).
Ben-Aharon, I., Gafter-Gvili, A., Paul, M., Leibovici, L., & Stemmer, S.M. (2008). Interventions for alleviating cancer-related dyspnea: A systematic review. Journal of Clinical Oncology, 26(14), 2396-2404.
The objective of this study was to systematically review the evidence for the efficacy of pharmacologic and nonpharmacologic treatments in alleviating dyspnea in patients with terminal cancer.
Databases searched were Cochrane Library up to 2007, MEDLINE (PubMed) (1966–2007), American Society of Clinical Oncology conference proceedings, and references of all included documents. In addition to databases, the search included the reference lists of key studies, the reference lists of 16 review articles on the topic, reference lists from 16 textbooks, and seven websites. Authors (15) of main investigations were contacted, and all members of the Association of Palliative Care and users of the www.palliativedrugs.com bulletin board were contacted for additional information and unpublished data.
Search keywords were opiate, opioid, morphine, benzodiazepine, furosemide, steroids, corticosteroids, oxygen, nonpharmacological, acupuncture, nursing, cancer, carcinoma, malignancy, dyspnea and breathlessness.
Studies were included in the review if they were a randomized controlled trial assessing dyspnea in patients with terminal cancer in which any intervention for dyspnea relief was compared with no intervention, placebo, or another intervention.
Studies were excluded if they were nonrandomized studies or trials in which only a minority of the patients had a cancer diagnosis.
Literature evaluated included 37 studies, plus one abstract initially reviewed. A final set of 18 studies was included; 7 assessed opioids, 6 assessed oxygen- or helium-enriched air, 1 assessed furosemide, and 4 assessed nonpharmacologic interventions. Meta-analysis was not completed due to the paucity of studies and heterogeneous outcome measures.
Sample Size Across Studies:
Sample Range Across Studies:
With respect to gender, age, and diagnosis within the sample, the opioids subgroup included both genders. The median age range was 56–73 years. The majority had primary lung cancer, and both opioid-tolerant and opioid-naïve participants were included.
The oxygen or helium subgroup included both genders. The median age range was 64–72 years. The majority had primary lung cancer.
No comment was available on gender or age for the nonpharmacologic subgroup, but the primary diagnosis was lung cancer.
The primary outcome was subjective dyspnea relief according to the visual analog scale (VAS) or dyspnea intensity according to the modified Borg scale. The secondary outcome was oxygen saturation and adverse effects.
Opioid Intervention:
Oxygen Intervention:
Furosemide Intervention:
Nonpharmacologic Interventions:
Acknowledging the paucity of evidence from randomized controlled trials to support the interventions is important.
Limitations of this review were
A major research opportunity exists to further document outcomes from nurse-led dyspnea interventions.
Ben-Aharon, I., Gafter-Gvili, A., Leibovici, L., & Stemmer, S.M. (2012). Interventions for alleviating cancer-related dyspnea: A systematic review and meta-analysis. Acta Oncologica (Stockholm, Sweden), 51, 996-1008.
The objective of this meta-analysis and systematic review was to evaluate the role of different interventions to alleviate dyspnea.
A total of 829 references were retrieved. The specific method of evaluation was not described, but the small sample size of most studies was noted.
Patients were undergoing end-of-life care.
Findings provide guidance regarding effectiveness of interventions for dyspnea in patients with cancer. These results demonstrate the effectiveness of opioids. Findings also confirm those of others that palliative oxygen is of no benefit for this symptom. Some reviews continue to suggest the use of palliative oxygen. This is not supported by evidence, and home oxygen therapy is generally not covered by insurance for patients who do not have hypoxemia. Unnecessary use can be costly to the patient. Evidence is limited regarding the effects of the addition of hypnotics to opioids in managing dyspnea. This is an area that could benefit from additional research.
Belmonte, R., Tejero, M., Ferrer, M., Muniesa, J.M., Duarte, E., Cunillera, O., & Escalada, F. (2011). Efficacy of low-frequency low-intensity electrotherapy in the treatment of breast cancer-related lymphoedema: A cross-over randomized trial. Clinical Rehabilitation, 26(7), 607–618.
To compare efficacy of low-frequency, low-intensity electrotherapy and manual lymphatic drainage in treatment of upper-limb lymphedema
Patients were randomized to two groups. Group A underwent electrotherapy therapy for 10 sessions followed by 10 sessions of manual drainage. Group B underwent manual drainage first and then received electrotherapy. There was a month washout period between treatments. Patients were assessed after every 10 treatment sessions. Electrotherapy was delivered with a system that provides massage with low-frequency electrical stimulation.
The study took place in an outpatient setting in Spain.
The study has clinical applicability for late effects and survivorship.
The study used a randomized crossover trial design.
There were no significant differences in outcomes between the two treatments.
There was no difference in benefits from manual lymphatic drainage and low-frequency, low-intensity electrotherapy.
Findings suggest there is no difference in efficacy of these two treatment approaches for management of arm lymphedema in patients with breast cancer.
Bell, R., Eccleston, C., & Kalso, E. (2003). Ketamine as an adjuvant to opioids for cancer pain. Cochrane Database of Systematic Reviews 2003, Issue 1. Art. No.: CD003351. DOI: 10.1002/14651858.CD003351.
The object of the systemic review was to assess the effectiveness of ketamine as an adjuvant therapy in treating cancer pain.
Medline (1996-2002); EMBASE (1980-2002); CancerLit (1966-2002); Cochrane Controlled Trials Registar and Database of Systematic Reviews (Cochrane Library, Issue 1, 2002); Specialized Registar of the Cochrane Pain, Palliative and Supportive Care Group (2001), PARDLARS (inhouse datadase of Pfizer UK, February 2002), hand searching reference lists
Two RCT met inclusion criteria. Two other RCT appeared to meet the criteria but were considered methodologically flawed. There were 32 case reports or open-label uncontrolled trials that could not be included.
Thirty patients, 17 men and 13 women, ages 21-69. Cancers included stomach, cervix, liver, lung, colon, pancreas, bladder, rectum, histiocytoma, and uterus. Study 1 with 20 had patients whose pain had been treated successfully with opioids. Study 2 had 10 whose pain had been unrelieved by their dose of morphine. Study 2 defined the pain as “neuropathic,” and the patients had a Karnofsky of 50 or more.
There was a reduction in pain scores for those receiving the ketamine. Four patients experienced hallucinations (most common adverse effect associated with ketamine). Two of these four patients also experienced a sensation of insobriety. All of these effects were relieved by diazepam.
Treatments evaluated:
Outcomes Measured:
The primary outcome measure was patient-reported pain intensity and pain relief, using validated measures on movement and at rest ( e.g., visual analog scale and verbal rating scale).
Secondary outcomes included: total opioid consumption, rescue medication, adverse events, study withdrawals, and dropouts.
Because of the small number of RCTs , the small sample sizes, and the lack of other acceptable research, there is insufficient evidence for the use of ketamine as an adjuvant to opioids to make a recommendation for practice.
Suggested for research are crossover designs, larger patient groups, comparisons with other opioids, comparisons of routes of administration, and clearly defined outcomes. Research into ketamine’s role as an NMDA antagonist also would be welcomed.
Bell, R., Eccleston, C., & Kalso, E. (2003). Ketamine as an adjuvant to opioids for cancer pain. Cochrane Database of Systematic Reviews 2003, Issue 1. Art. No.: CD003351.
DATABASES USED: MEDLINE (1996–2002); EMBASE (1980–2002); CANCERLIT (1966–2002); Cochrane Controlled Trials Register and Database of Systematic Reviews (Cochrane Library, Issue 1, 2002); Specialized Register of the Cochrane Pain, Palliative and Supportive Care Group (2001); PARDLARS (in-house database of Pfizer UK, February 2002); hand-searching reference lists
EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Two RCTs met inclusion criteria. Two other RCTs appeared to meet the criteria but were considered methodologically flawed. Thirty-two case reports or open-label uncontrolled trials could not be included.
FINAL NUMBER STUDIES INCLUDED = 2
TOTAL PATIENTS INCLUDED IN REVIEW: 30
KEY SAMPLE CHARACTERISTICS: Seventeen men and 13 women aged 21–69 years. Cancers included stomach, cervix, liver, lung, colon, pancreas, bladder, rectum, histiocytoma, and uterus. The first study included 20 patients whose pain had been treated successfully with opioids. The second study included 10 patients whose pain had been unrelieved by their dose of morphine. In the second study, pain was defined as “neuropathic,” and the patients had a Karnofsky score of 50 or more.
Pain scores were reduced in those patients receiving ketamine. Four patients experienced hallucinations (most common adverse effect associated with ketamine). Two of those four patients also experienced a sensation of insobriety. All of these effects were relieved by diazepam.
The following treatments were evaluated.
The primary outcome measure was patient-reported pain intensity and pain relief, using validated measures on movement and at rest (e.g., visual analog scale and verbal rating scale). Secondary outcomes included total opioid consumption, rescue medication, adverse events, study withdrawals, and dropouts.
The objective of the systematic review was to assess the effectiveness of ketamine as an adjuvant therapy in treating cancer pain. Because of the small number of RCTs, small sample sizes, and lack of other acceptable research, evidence is insufficient to make the use of ketamine as an adjuvant to opioids a recommendation for practice.
Suggested for research are crossover designs, larger patient groups, comparisons with other opioids, comparisons of routes of administration, and clearly defined outcomes. Research into ketamine’s role as an NMDA antagonist also would be welcomed.
Bell, R.F., Eccleston, C., & Kalso, E.A. (2012). Ketamine as an adjuvant to opioids for cancer pain. Cochrane Database of Systematic Reviews 2012, Issue 11. Art. No.: CD003351.
To determine the efficacy and adverse effects of ketamine as an adjuvant to opioids in the treatment of cancer pain
Databases searched were CENTRAL, MEDLINE, EMBASE, PubMed, and the Pfizer Product Information Database.
Studies were included in the review if they
Studies were excluded if they had fewer than 10 participants.
A total of 120 references were retrieved. Studies were selected based on criteria, assessed independently, reviewed by two reviewers, and chosen for inclusion by three independent reviewers.
Current evidence is insufficient to assess the benefits and harms of ketamine as an adjuvant to opioids in the relief of cancer pain because of the small number of trials with low sample sizes.
Although studies suggest that ketamine may be a helpful adjuvant therapy to improve pain and decrease opioid requirements in patients with cancer, more studies are needed with larger sample sizes and control groups. Evidence is lacking to recommend ketamine in practice.
Belgacem, B., Auclair, C., Fedor, M.C., Brugnon, D., Blanquet, M., Tournilhac, O., & Gerbaud, L. (2013). A caregiver educational program improves quality of life and burden for cancer patients and their caregivers: A randomised clinical trial. European Journal of Oncology Nursing, 17, 870–876.
No difference was seen in quality of life scores between the control (N = 34) and experimental (N = 33) patient-caregiver dyad groups at the first testing. Evaluation (pre- and post-test scores) supported improved quality-of-life scores in the experimental group patient-caregiver dyads as compared to those in the control group. Patients in the experimental group showed significant improvement on two of six dimensions (physical role [p = 0.039] and general health [p = 0.037] on the quality-of-life measure. Experimental group caregivers showed significant improvement on six of eight dimensions (physical role, emotional role, vitality, mental health, social functioning, and general health, all p < 0.05) on the quality-of-life measure. The average score of burden of care in the experimental group (M = 16, SD = 9.9) was significantly lower than that of control group (M = 31.4, SD = 14.9) at last evaluation (p < 0.001). Evolution scores for burden also showed significantly (p = 0.004) less perceived burden among experimental group caregivers as compared to control group caregivers. Patient satisfaction scores of patients in the experimental and control groups showed no difference, except patients in the experimental group showed a significant improvement in relationship with nurses (p = 0.037) because of program involvement.
Nurse-provided educational interventions tailored to caregiver needs and patient expectations may minimize caregiver burden and improve patient and caregiver quality of life. These interventions, if provided during patients’ acute setting care, may pave the way for more effective patient home care by informed and involved caregivers.
Nurses who deliver evidence-based, tailored educational interventions to family cancer caregivers may increase patient-caregiver quality of life and minimize caregiver burden during cancer care. Stronger nurse-patient relationships, based on interaction during caregiver task teaching, may facilitate patient care satisfaction and coping during the cancer experience.
Beikmoradi, A., Najafi, F., Roshanaei, G., Pour Esmaeil, Z., Khatibian, M., & Ahmadi, A. (2015). Acupressure and anxiety in cancer patients. Iranian Red Crescent Medical Journal, 17, e25919.
To investigate the effects of acupressure on anxiety in patients with cancer
Patients were randomly assigned to acupressure, sham acupressure, or control groups. Control group patients received usual care. The acupressure group had pressure applied at nine points for two minutes each by a research assistant. Sham acupressure was also given at nine different points on the body. Patients received 10 sessions of sham or actual acupressure. Study measures were obtained at baseline, after session 5, and after session 10.
Double-blinded, sham-controlled, randomized trial
Mean anxiety scores in the acupressure group declined over the three study measurement periods (p = 0.001). Anxiety scores in the sham group also declined somewhat. Anxiety levels in the control group increased over time. An analysis of variance showed that acupressure was associated with a significant reduction in state anxiety scores and a significant difference in comparison to the control group patients (p < 0.0001). There was no significant difference between acupressure and sham acupressure changes.
Both sham and actual acupressure were associated with reductions in anxiety scores.
The findings of this study suggest that acupressure may be of some benefit in the short-term management of anxiety among patients with cancer. The findings regarding the effects of sham acupressure suggest there may be a placebo effect involved. Additional well-designed research would be helpful to demonstrate the role of acupressure in the management of anxiety.
Beijer, S., Hupperets, P. S., van den Borne, B. E., Wijckmans, N. E., Spreeuwenberg, C., van den Brandt, P. A., & Dagnelie, P. C. (2010). Randomized clinical trial on the effects of adenosine 5'-triphosphate infusions on quality of life, functional status, and fatigue in preterminal cancer patients. Journal of Pain and Symptom Management, 40, 520–530.
To investigate the effects of adenosine 5'-triphosphate (ATP) infusions on quality-of-life (QOL) parameters in patients with preterminal cancers of mixed tumor types.
Patients were randomized to the usual care control group with standard nutritional advice or to the intervention of usual care, nutritional advice, and ATP infusion. An eight- to 10-hour ATP infusion was given weekly, with a maximum dose of 50 µ/kg/minute.
The study was a randomized, controlled trial.
Better survival was observed during the eight-week intervention in the ATP group. The rationale was that palliative cancer drugs cause serious side effects. The authors concluded that that may be an advantage of the ATP treatment.
The study provided little useful information for nurses.