Mao, J.J., Farrar, J.T., Bruner, D., Zee, J., Bowman, M., Seluzicki, C., . . . Xie, S.X. (2014). Electroacupuncture for fatigue, sleep, and psychological distress in breast cancer patients with aromatase inhibitor-related arthralgia: A randomized trial. Cancer, 23, 3744–3751.
To examine electroacupuncture (EA) compared to sham acupuncture (SA) and a waitlist control (WLC) group to determine effectiveness on fatigue, sleep disturbance, depression, and anxiety in postmenopausal breast cancer survivors who reported joint pain, or arthralgia, related to aromatase inhibitors (anastrazole, letrozole, exemestane)
Acupuncture interventions were administered by two licensed acupuncturists (not physicians). Ten treatments were administered over eight weeks with two treatments during each of the first two weeks followed by one treatment per week for the following six weeks. The EA and SA treatments were administered by the same two acupuncturists. Procedures for the two groups differed in the placement of the acupuncture needles and actual versus sham electrical stimulation using a transcutaneous electrical nerve stimulation (TENS) unit. The same timing and duration of treatments was used for each group.
Three-group randomized controlled trial comparing EA, SA, and WLC.
Four measurement tools were used: the Brief Pain Inventory (BPI); the Brief Fatigue Inventory (BFI); the Pittsburgh Sleep Quality Index (PSQI); and the Hospital Anxiety and Depression Scale (HADS). A priori primary outcome reported pain intensity and interference. A priori secondary outcome reported fatigue, sleep, and psychological distress (anxiety, depression).
Measurements were repeated at weeks 4, 8, and 12. There was significant (p = 0.0095) improvement in the fatigue score after EA, no improvement with SA, and greater reduction in fatigue than the WLC group. There were nonsignificant improvements in sleep in the EA and SA groups compared to the WLC group. There was significant (p = 0.04) improvement in the EA group but the SA group on the HADS anxiety score compared to the WLC group; a nonsignificant improvement continued in the EA group at week 8, whereas week 12 showed a significant (p = 0.006) improvement in the EA and WLC groups. EA and SA group improvements in depression scores were significant (p = 0.015 and p = 0.0088, respectively) compared with the WLC group; EA and SA significantly (p = 0.0031m and p = 0.0056, respectively) improved scores at week 8, and scores did not change at week 12.
EA produced improvements by reducing fatigue, anxiety, and depression scores. SA produced improvements in depression scores only. Acupuncture with electronic stimulation may be an effective treatment for pain and the nonpain symptoms of fatigue, sleep disturbance, and depression associated with AIs. Additional research is encouraged.
Acupuncture with electrical stimulation should be considered a viable treatment option for patients with breast cancer taking AIs who complain of joint pain. Large, randomized, controlled research studies are needed to develop evidence for the efficacy of EA in breast and other cancers. Drug and symptom cluster correlations must be deconstructed.
Mao, J.J., Xie, S.X., Farrar, J.T., Stricker, C.T., Bowman, M.A., Bruner, D., & DeMichele, A. (2014). A randomised trial of electro-acupuncture for arthralgia related to aromatase inhibitor use. European Journal of Cancer, 50, 267–276.
To test the hypothesis that electroacupuncture (EA) would improve function and reduce arthralgia compared to usual care
Patients were randomized to wait-list control, EA, or sham acupuncture (SA) groups. Acupuncture was given twice a week for two weeks, then weekly, for a total of 10 treatments over eight weeks. SA treatment frequency and duration were the same as for EA. Study assessments were done at baseline, after eight weeks, and at week 12.
At week 8 and week 12, the EA group had a greater reduction in pain severity and pain interference compared to the wait-list control group (p < .001). The EA group also had greater improvement in DASH scores and outcomes, as measured by the WOMAC index compared to controls. The SA group also had a significantly greater reduction in pain severity and interference compared to controls at week 8 and week 12 (p < .005). No significant differences were seen between the SA and EA groups.
EA and SA were associated with reduction in arthralgia pain severity and interference and improvement in joint disability measures.
Findings suggest that EA and placebo acupuncture resulted in reduced pain from arthralgia in patients receiving aromatase inhibitors. Although this study was well designed, the sample size was small, and a substantial number of participants dropped out. Placebo effects of acupuncture or SA may help to alleviate arthralgia pain in these patients, and this approach may be acceptable or preferred by some patients.
Mao, H., Mao, J.J., Guo, M., Cheng, K., Wei, J., Shen, X., & Shen, X. (2016). Effects of infrared laser moxibustion on cancer-related fatigue: A randomized, double-blind, placebo-controlled trial. Cancer, 122, 3667–3672.
To evaluate the safety and efficacy of laser moxibustion for cancer-related fatigue
Moxibustion is a modality of acupuncture that involves burning the herb Artemisia vulgaris on or above the skin at acupoints. This provides heat stimulation instead of stimulation by needles. Infrared laser moxibustion is an approach using laser devices to irradiate acupoints at about 2 cm away from the skin's surface. Patients were randomly assigned to receive real or sham laser moxibustion for 20 minutes three times per week for four weeks. The laser operator was blinded; because the infrared laser is colorless, neither the operator nor the patient could see it. For the sham group, the laser source was turned off. Fatigue was measured at baseline and at weeks 2, 4, and 8.
PHASE OF CARE: Multiple phases of care
Double-blind, sham-controlled, randomized, controlled trial
Brief Fatigue Inventory (BFI), Chinese version
At week 2, the fatigue score in the moxibustion group was lower (3.8 versus 4.7, Cohen’s d = 0.685, p = 0.044). At week 4, fatigue was also lower in the moxibustion group (3.01 versus 4.40, Cohen's d = 1.14, p = 0.002), and at week 8, the moxibustion group had lower fatigue as well (3.03 versus 4.26, Cohen's d = 0.886, p = 0.006). No serious adverse events were reported.
The findings suggest that laser moxibustion may be helpful in relieving cancer-related fatigue.
Laser moxibustion may be another option to combat cancer-related fatigue. This is a painless, noninvasive intervention that warrants further investigation.
de Melo Manzi, N., de Campos Pereira Silveira, R.C., & dos Reis, P.E. (2015). Prophylaxis for mucositis induced by ambulatory chemotherapy: Systematic review. Journal of Advanced Nursing, 72, 735–746.
STUDY PURPOSE: To systematically review evidence regarding interventions used to prevent chemotherapy-induced oral mucositis (OM)
PHASE OF CARE: Active antitumor treatment
Based on this review, the strongest evidence was in favor of cryotherapy in patients receiving 5-FU. The evidence was insufficient in other interventions to demonstrate a benefit.
Very few studies were included, and why this search did not yield a larger number of studies for some of these interventions was unclear. Exclusion criteria may have eliminated many. Most included studies had small sample sizes.
The findings support the use of cryotherapy for the prevention of OM in patients receiving 5-FU. Although not studied extensively, this intervention should have benefit in patients receiving any agent with a short half-life. The amount of ice chips, etc. used and the duration of the cryotherapy varied. Multinational Association of Supportive Care in Cancer guidelines recommend a 30-minute duration and an amount of ice that can easily be moved around in the mouth.
Manusirivithaya, S., Sripramote, M., Tangjitgamol, S., Sheanakul, C., Leelahakorn, S., Thavaramara, T., et al. (2004). Antiemetic effect of ginger in gynecologic oncology patients receiving cisplatin. International Journal of Gynecologic Cancer, 14, 1063-1069.
To determine the potential antiemetic effect of ginger in cisplatin-induced emesis
Patients were randomized to one of two groups. In regimen A, patients received 1 g of ginger per day for five days starting on the first day of chemotherapy. In regimen B, patients received a placebo on day one and metoclopramide on days two through five.
The study was conducted in Bangkok, Thailand.
Investigators assessed nausea and vomiting on day one. On days 2-5, patients recorded the presence and intensity of emetic episodes on diary cards.
In regimen A, no effect was found in acute or delayed treatment. In regimen B, ginger had the same control as 40 mg metoclopramide for delayed nausea.
Mantovani, G., Massa, E., Astara, G., Murgia, V., Gramignano, G., Lusso, M.R., … Maccio, A. (2003). Phase II clinical trial of local use of GM-CSF for prevention and treatment of chemotherapy and concomitant chemoradiotherapy-induced severe oral mucositis in advanced head and neck cancer patients: An evaluation of effectiveness, safety and costs. Oncology Reports, 10, 197-206.
To evaluate a granulocyte-macrophage colony-stimulating factor (GM-CSF) mouthwash in the prophylactic and curative settings of oral mucositis (OM)
All patients were given 300 mcg of granulocyte-macrophage colony-stimulating factor (GM-CSF) in 300 ml of water; patients were instructed to rinse and gargle with the mouthwash for as long as possible, three times daily (morning, midday, and before bedtime). Patients were instructed to not eat, drink, or rinse with another mouthwash for at least one hour afterward. Patients in the prophylactic group also received amifostine (500 mg IV). Patients in the curative group were treated from the appearance of mucositis until two days after clinical resolution.
This was an open, nonrandomized, phase II study.
Mantovani, G., Macciò, A., Madeddu, C., Gramignano, G., Lusso, M. R., Serpe, R., . . . Deiana, L. (2006). A phase II study with antioxidants, both in the diet and supplemented, pharmaconutritional support, progestagen, and anti-cyclooxygenase-2 showing efficacy and safety in patients with cancer-related anorexia/cachexia and oxidative stress. Cancer Epidemiology, Biomarkers and Prevention, 15, 1030–1034.
The integrated treatment consisted of the following components:
Patient outcomes were assessed at baseline and one, two, and four months.
Not identified
Patients were undergoing the active treatment phase of care.
This was an open, early-phase II study.
Multidimensional Fatigue Symptom Inventory–Short Form (MFSI-SF)
Compared to baseline scores, fatigue outcomes improved at two months (p = 0.22) and more so at four months (p = 0.004). No correlation existed between changes in fatigue and changes in any other variable studied.
Mantovani, G., Macciò, A., Madeddu, C., Gramignano, G., Serpe, R., Massa, E., . . . Floris, C. (2008). Randomized phase III clinical trial of five different arms of treatment for patients with cancer cachexia: interim results. Nutrition, 24, 305–313.
All patients received basic treatment with polyphenols (300 mg/day) from alimentary sources (e.g., onions, apples, oranges, red wine, and green tea) or supplementary tablets. Patients also received antioxidant agents (a-lipoic acid and carbocisteine), as well as vitamins A, C, and E, orally. All patients then were randomized to one of the following five treatment arm interventions:
The planned treatment duration was four months. Patient outcomes were evaluated at 4, 8, 16, and 24 weeks.
Policlinico Universitario and Ospedale Oncologico Regionale, Cagliari, Italy
The study was a randomized, phase II, two-center clinical trial with five treatment arms.
Multidimensional Fatigue Symptom Inventory–Short Form (MFSI-SF)
When comparing baseline and posttreatment measures, statistically significant improvements in fatigue outcomes were observed in the L-carnitine treatment arm (p = 0.039) and the MPA/MA plus pharmacologic nutritional support, L-carnitine, and thalidomide arm (p = 0.015). Fatigue worsened significantly in patients receiving EPA-enriched oral supplementation treatment (p = 0.051).
Mantovani, G., Maccio, A., Madeddu, C., Serpe, R., Massa, E., Dessi, M., . . . Contu, P. (2010). Randomized phase III clinical trial of five different arms of treatment in 332 patients with cancer cachexia. Oncologist, 15, 200–211.
To determine the most effective and safest treatment to improve primary endpoints of lean body mass, resting energy expenditure, and fatigue in patients with cancer-related anorexia-cachexia syndrome
To determine the effects on secondary endpoints of appetite, quality of life, grip strength, Glasgow Prognostic Score, and proinflammatory cytokines
All patients were given the following standard treatment orally via pills or dietary intake:
Patients were randomly assigned to one of the following five treatment arms:
Planned treatment duration was four months.
The multisite study was conducted in Italy.
The study was a phase III, prospective, randomized trial.
Results demonstrate efficacy of a combined treatment approach in cancer cachexia syndrome.
Results seem to confirm that cancer cachexia, as a multidimensional syndrome, is likely to yield success with a multifactorial approach.
Results appear to confirm thinking that cachexia is driven by inflammatory cytokines and that drugs that down-regulate the production and/or release of proinflammatory cytokines can be effective in reversing the symptoms of the syndrome.
It is noted that the drugs and dietary supplements used are low cost.
Combined treatments used here may indicate an additive or synergistic effect of the agents.
Mansouri, P., Haghighi, M., Beheshtipour, N., & Ramzi, M. (2016). The effect of aloe vera solution on chemotherapy-induced stomatitis in clients with lymphoma and leukemia: A randomized controlled clinical trial. International Journal of Community Based Nursing and Midwifery, 4, 119–126. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4876780
To assess the effect of aloe vera solution on stomatitis and its pain intensity in patients undergoing chemotherapeutic procedures
In a randomized, controlled clinical trial, 64 patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) undergoing chemotherapy were randomly divided into a control and intervention group. The intervention group was asked to wash their mouths with 5 mls of aloe vera solution for two minutes twice a day for 14 days. The control group used the ordinary mouthwashes recommended in hematologic centers.
PHASE OF CARE: Active antitumor treatment
Randomized, controlled clinical trial patients were randomly divided into a control and an intervention group.
Aloe vera solution mouthwash significantly reduced the intensity of stomatitis and its pain in the intervention group compared to the control group. On day one, no difference existed; on the other days, there was a significant difference (days 3–14: p = 0.001 for stomatitis intensity, p = 0.001 for pain).
Aloe vera solution might improve patients’ nutritional status, reduce stomatitis and its pain intensity, and lead to satisfaction.
Aloe vera mouthwash can be useful in preventing and treating stomatitis in patients with chemotherapy-induced stomatitis without any side effects.