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.

• N = 61   
• MEAN AGE = 59.3 years
• MALES: 46.1%, FEMALES: 53.9%
• CURRENT TREATMENT: Chemotherapy, radiation, combination radiation and chemotherapy
• KEY DISEASE CHARACTERISTICS: Multiple tumor types—breast, lung, and gastrointestinal were more prevalent.
• OTHER KEY SAMPLE CHARACTERISTICS: The majority were undergoing current treatment; 35.9% were in the survivorship phase after curative treatment. Baseline fatigue was 4.5; 5.03 was the average across groups.

• SITE: Single site   
• SETTING TYPE: Not specified    
• LOCATION: China

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.

• Small sample (< 100)
• Subject withdrawals ≥ 10% 
• The dropout rate was over 20% but mostly because of disease progression.
• The follow-up period was relatively short.

Laser moxibustion may be another option to combat cancer-related fatigue. This is a painless, noninvasive intervention that warrants further investigation.

STUDY PURPOSE: To systematically review evidence regarding interventions used to prevent chemotherapy-induced oral mucositis (OM)

• FINAL NUMBER STUDIES INCLUDED = 20
• TOTAL PATIENTS INCLUDED IN REVIEW = 1,626
• SAMPLE RANGE ACROSS STUDIES: 16–326 patients
• KEY SAMPLE CHARACTERISTICS: Various patient types

PHASE OF CARE: Active antitumor treatment

• Cryotherapy was evaluated in four studies. Cryotherapy reduced the seriousness and incidence of OM. Three of these were among patients receiving 5-fluorouracil (5-FU).   
• Limited research evidence for oral care in general and lack of consistent definition and components of oral care
• Two palifermin studies were included, showing its effectiveness for the prevention of OM; however, they were of small sample sizes.
• Two studies looked at allopurinol and had mixed results.
• Two studies examined the use of chlorhexidine and had mixed results.

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.

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 consisted of 48 patients.
• All patients were female.
• All patients were being treated for gynecologic cancers and were receiving cisplatin chemotherapy.

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.

• The sample size was small.
• Comparing antiemetics was difficult because the study did not use 5-HT₃ antiemetics.

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.

• The study reported on 68 patients with 46 in the prophylaxis group and 22 in the curative group.
• All patients were treated with chemotherapy and radiation therapy. Most patients were diagnosed with advanced head and neck cancer.

This was an open, nonrandomized, phase II study.

• The National Cancer Institute (NCI) Common Toxicity Criteria for oral mucositis were used.
• The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)–Head and Neck (H&N) 35 was used.

• Duration of mucositis was 8.7 in the prophylaxis group and 11.5 in the curative group (p = 0.089).
• Patients had a lower mean grade of OM on day 3 (p = 0.012) and day 6 (p = 0.007).
• Only 50% of patients in the prophylaxis group developed mucositis.

• The QLQ was only administered to those in the prophylactic arm of study.
• Too many factors could have influenced patient outcomes. No control group was included.
• The  two groups had different sizes.
• Determining significance is difficult to based on the study design.

The integrated treatment consisted of the following components:

1. High polyphenols content (400 mg)
2. Antioxidant treatment (300 mg/d a-lipoic acid + 2.7 g/d carbocisteine lysine salt + 400 mg/d vitamin E + 30,000 IU/d vitamin A + 500 mg/d vitamin C)
3. Pharmaconutritional support enriched with 2 cans per day (n-3) ​polyunsaturated fatty acids (PUFA) (eicosapentaenoic acid and docosahexaenoic acid), 500 mg/d medroxyprogesterone acetate, and 200 mg/d selective cyclooxygenase-2-inhibitor celecoxib.

Patient outcomes were assessed at baseline and one, two, and four months.

• The sample included 39 patients with cancer-related anorexia/cachexia syndrome (CACS).
• Mean age was 58.9 years (range 42–78).
• The majority of patients were male (n = 23).
• Patients had multiple tumor sites, but the most common was head and neck (43.6%); 97.4% were stage IV.

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.

• The study lacked a neutral comparison group.
• The study had a small sample size.

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:

1. Progestational agent medroxyprogesterone acetate (MPA) 500 mg/day or megestrol acetate (MA) 320 mg/day
2. Oral supplementation of eicosapentaenoic acid (EPA)-enriched nutritional supplements, with docosahexaenoic acid, high-calorie, and high-protein content
3. L-carnitine 4 g/day, orally
4. Thalidomide 200 mg/day, orally
5. MPA or MA plus pharmacologic nutritional support, L-carnitine, and thalidomide.

The planned treatment duration was four months. Patient outcomes were evaluated at 4, 8, 16, and 24 weeks.

• The sample was comprised of 125 adult patients with cancer and cancer cachexia (mean age = 69.1 years [range 35–80]).
• The male/female ratio was 74/51.
• A majority (83%) of patients experienced more than 5% weight loss before study entry and were stage IV (94.4%).
• Patients had varied diagnoses, the most common being lung (14.4%) and breast (14.4%) cancer.
• Patients were excluded if they were women of child-bearing age, had significant comorbidities, had a mechanical obstruction to feeding, underwent medical treatments that induced significant changes to body metabolism or weight, or had contradiction to MPA or MA.

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).

• No placebo arm was included because an approved drug for cancer cachexia treatment was available at the time of study (MPA or MA).
• The results were from an interim report.

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:

• 300 mg/day polyphenols
• 300 mg/day lipoic acid
• 2.7g/day carbocysteine
• 400 mg/day vitamin E
• 30,000 IU/day vitamin A
• 500 mg/day vitamin C

Patients were randomly assigned to one of the following five treatment arms:

1. 500 mg/day medroxyprogesterone acetate (MPA) or 320 mg/day megestrol acetate (MA) (considered equivalent)
2. An eicosapentaenoic acid (EPA)-enriched nutritional supplement (2 cartons/day for 2.2 g EPA)
3. 4 g/day L-carnitine
4. 200 mg/day thalidomide
5. Combination of all of the above treatments

Planned treatment duration was four months.

• The study reported on 332 patients. 
• Mean age across all study groups ranged from 60.6 to 62.8 years. There were no differences between groups. All patients were older than 18 years of age.
• The sample was 55% male and 45% female.
• Patients were diagnosed with any type of cancer and experienced loss of more than 5% of their ideal or preillness body weight in the previous three months.
• All patients had stage III or IV disease; 50% had an Eastern Cooperative Oncology Group (ECOG) performance status of 0–1, and 50% had a performance status of 2–3; and 78% were receiving concomitant palliative chemotherapy.

The multisite study was conducted in Italy.

The study was a phase III, prospective, randomized trial.

• Lean body mass (LBM) was assessed by bioelectrical impedance in all patients and by dual-energy x-ray absorptiometry (DEXA) and regional computed tomography (CT) in some patients.
• Resting energy expenditure (REE) was assessed by indirect calorimetry.
• Fatigue was assessed with the Multidimensional Fatigue Symptom Inventory–short form.
• Appetite was assessed via a visual analog scale (VAS).
• Quality of life (QOL) was assessed via the European Oncology Research and Treatment of Cancer Core Quality of Life questionnaire (EORTC QLQ-C30).
• Multiple cytokines (interleukin, tumor necrosis factor) were evaluated.
• Total energy expenditure was calculated as REE plus measured activity expenditure from an electronic armband device.
• ECOG performance status was reported.

• Twelve patients withdrew due to disease progression. The drop-out rate was not significantly different between study arms.
• LBM measured by DEXA (p = 0.015) and CT (p = 0.001) increased in arm 5.
• REE decreased significantly in arm 5 (p = 0.047).
• Appetite increased significantly in arm 5 (p = 0.003).
• Fatigue decreased significantly in arm 5 (p = 0.047).
• ANOVA and post hoc analysis showed a significant difference in REE (p = 0.028) and fatigue (p = 0.035) findings in arm 5 compared to other groups.
• There was a trend toward increased grip strength in arms 3, 4, and 5.
• ECOG performance status increased significantly in arms 3, 4, and 5 (p </= 0.0001), ranging from a 0.2 to 0.05 average score reduction.
• There were no significant changes in overall QOL measurement.
• Arms 4 and 5 showed reduction in cytokines measured.
• Two patients with grade 3 or 4 diarrhea were reported in arms 3 and 5. Toxicity was comparable among treatment arms and was negligible.

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.

• Results may not be readily generalizeable for broad clinical application since the treatment may appear difficult, particularly in cachectic patients who often have an already huge drug burden.
• This study was done in patients with advanced disease and a documented cachexia syndrome. Findings may not be applicable to other patient groups for management of appetite and fatigue.

Combined treatments used here may indicate an additive or synergistic effect of the agents.

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.

• N = 64   
• AGE = Control: 47.78 years (SD = 18.28 years), intervention: 46.25 years (SD = 18.17)
• MALES: 100% 
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: Chemotherapy-induced stomatitis

• SITE: Single site   
• SETTING TYPE: Outpatient    
• LOCATION: Shahid Motahari Clinic

PHASE OF CARE: Active antitumor treatment

Randomized, controlled clinical trial patients were randomly divided into a control and an intervention group.

• World Health Organization stomatitis intensity survey checklist
• Visual analog scale (VAS), a standard tool for measuring pain intensity

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.

• Risk of bias (no blinding)
• Unintended interventions or applicable interventions not described that would influence results
• Study participants were all male.
• No mention of the type of chemotherapy or specific protocols uses
• No information about use of pain medication or oral care procedures

Aloe vera mouthwash can be useful in preventing and treating stomatitis in patients with chemotherapy-induced stomatitis without any side effects.

Evaluate the effect of oral zinc sulfate for prevention of chemotherapy-induced oral mucositis in patients undergoing hematopoietic stem cell transplantation (HSCT).

Zinc sulfate at 440 mg/day provided orally in two doses every 12 hours, or placebo was provided beginning the day before starting the conditioning regimen. The capsules were administered by hospital staff. Patients were followed every day. All patients received the same prophylaxis regimen, which included 20 drops nystatin every three hours, chewable sucralfate 500 mg every eight hours, and mouthwashes such as chlorhexidine, amphotericin, and diluted povidone iodine every three hours.

The study was comprised of 60 patients, with a mean age 30.87 and 27.13 years per group.

Female 30%, Male 70%

All patients were receiving conditioning regimens for HSCT.

Single site, inpatient setting, Tehran, Iran

Randomized, double blind, placebo controlled

WHO mucositis grading scale

There were no significant differences between groups in mucositis grade, time of onset, or duration.

Zinc sulfate did not show any benefit for the prevention and management of oral mucositis.

Small sample <100

Findings suggest that oral zinc sulfate is not beneficial for oral mucositis induced by high-dose chemotherapy for patients undergoing HSCT. Efficacy of zinc sulfate in other patient populations is not clear.

To investigate whether cognitive-behavioral therapy (CBT) can help survivors of breast cancer in effectively managing menopausal symptoms.

The intervention consisted of six 90-minute weekly sessions with group discussions, handouts, weekly homework, and paced breathing and relaxation practice—along with an audio CD to practice paced breathing and relaxation at home daily—in addition to usual care. The control group received usual care and follow-up by an oncologist or clinical nurse specialist every six months. Assessments took place at baseline, nine weeks after randomization (typically two weeks after treatment), and 26 weeks after randomization. All sessions were audio recorded, and a 10% random sample of the tapes was reviewed to evaluate the intervention.

• The study enrolled 88 English-speaking women with breast cancer who were randomized into blocks, stratified by age (younger than 50 years and 50 years or older).
• Patients reported a minimum of 10 problematic episodes of hot flashes per week for a duration of two months or more.

• Mutlisite
• Outpatient
• Breast clinics in London, England

• Patients were undergoing the transition phase of care after initial treatment.
• The study has clinical applicability for palliative and end-of-life care.

This was a triple-blinded, randomized, controlled trial.

• Sternal Skin Conductance (SSC) for physiological symptoms from hot flashes  
• SF-36® health-related quality-of-life ratings
• Women’s Health Questionnaire (WHQ)
• Adherence was measured by the number of sessions attended and the number of times that a patient practiced relaxation or paced breathing each week.

Night sweats problem rating scores at 9 and 26 weeks were lower in the CBT group than they were in the usual care group, with a mean difference between groups of –1.67 (95% confidence interval [CI] [–2.43, –0.91]; p < .0001). These scores also declined over time in the control group. There were no differences between groups in hot flush frequency, night sweats frequency, or SSC measures. Those receiving the CBT intervention reported less sleep problems (adjusted mean difference (AMD) = –0.16; 95% CI [–0.29, –0.02]), anxiety (AMD = –0.16; 95% CI [–0.29, –0.02]), and better memory and concentration (AMD = –0.14; 95% CI [–0.26, –0.02]).

The findings suggest that group CBT improved patients’ perceptions of the degree to which hot flashes were a problem but did not appear to affect the actual frequency or objective measures of hot flashes. Group CBT appeared to have a small size of effect on sleep problems, anxiety, and other self-reported outcomes.

• The study had a small sample size, with less than 100 patients.
• No attentional control was used.
• Specific AMD calculation was not described, so it is not clear how well this represents an effect size. 
• Measures for anxiety and other outcomes were limited.

This study provides some supportive evidence for the benefit of cognitive-behavioral approaches. Group CBT may have a benefit in managing hot flashes and other symptoms through altered perceptions of the degree to which these symptoms are seen as problematic. Health professionals, such as breast cancer nurses or clinical nurse specialists trained in CBT, can improve long-term health outcomes for patients with breast cancer, and CBT could be incorporated into breast cancer survivorship programs.