The study was conducted to investigate post-hoc the potential impact of erythropoietin on cognitive function following chemotherapy for breast cancer.

Patients were randomized when their hemoglobin (Hgb) level decreased to ≤ 12 g/dL. Depending on the remaining duration of chemotherapy, erythropoietin was administered for a period of time between 16 or 28 weeks. Patients were randomized to receive either 40,000 units of erythropoietin weekly or the standard of care.

• All participants were female and had breast cancer.
• Participants were selected from a primary study group receiving adjuvant chemotherapy.
• The number of participants was 87.
• The number of participants in the treatment group (erythropoietin arm) was 45.
• The number of participants in the control group (standard care) was 42.
• Participants spent an average of 23 months in the intervention group and 24 months in the standard-of-care group. 

This multi-site study took place in Canada.

The study was a randomized, controlled trial.

• Primary Cognitive Endpoint: Proportion with moderate-severe cognitive impairment at 12–30 months following completion of chemotherapy as measured by High Sensitivity Cognitive Screen (HSCS) for memory, language, attention, concentration, visual motor, spatial, and self-regulation
• Secondary Cognitive Endpoint: Proportion that scored in lowest quartile of any of four variables in the Hopkins Verbal Learning test–Revised (HVLT-R) for total recall, delayed recall percent retained, and discrimination index
• Functional Assessment of Cancer Therapy (FACT)-F for cancer-related quality of life specific to symptoms of fatigue
• Hospital Anxiety and Depression Scale (HADS) for anxiety and depression.

Participants showed no improvement in cognitive function or fatigue, as measured by the HSCS or HVLT-R. There was reported improvement in quality of life.

The study failed to demonstrate a protective effect of erythropoietin on cognitive dysfunction after chemotherapy in survivors of breast cancer.

• The study had a small sample size, given the variability in chemotherapy regimens and use of hormonal therapy.
• No baseline testing of cognitive function was conducted.
• The study lacked a control group.
• There were significant differences between groups in overall quality-of-life, anxiety, and depression scores.
• The selection of the delayed 12–30 month time frame may not have been the ideal time for assessment of the impact of erythropoietin on cognitive function.
• HSCS has not been shown to be a very sensitive test for detecting subtle cognitive impairments in the sample population. 

To evaluate the effects of electroacupuncture (EA) versus gabapentin (GP) for hot flashes among survivors of breast cancer, with a specific focus on the placebo, using sham acupuncture (SA) and placebo pills (PP), and monitoring nocebo effects.

• N = 120  
• AGE RANGE: 31–79 years
• MEAN AGE = 52.3 years (SD = 8.5 years)
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: The study included women with breast cancer (stages I–III) who were free of disease and who have at least two hot flashes each day. Women could not be receiving active chemotherapy/radiation therapy and could be on hormonal therapy; however, the hormonal therapy could not have been initiated or changed within four weeks of starting the study.
• OTHER KEY SAMPLE CHARACTERISTICS: Women who were pregnant, breastfeeding, or anticipated a change in hormonal therapy were not included, neither were women receiving coumadin, women who had a bleeding disorder, women who were receiving an anticonvulsant, women who had taken gabapentin in the past for hot flashes, or women who had renal failure in the prior 12 months. 74.2% of women were Caucasian; 22.5% were African American; 87.5% were postmenopausal; 25% had surgically induced menopause; 39.2% had chemotherapy-induced menopause; 67.5% were receiving hormonal therapy; and 25% were receiving an antidepressant.

• SITE: Single site    
• SETTING TYPE: Outpatient    
• LOCATION: Abramson Cancer Center of the University of Pennsylvania in Philadelphia

• PHASE OF CARE: Transition phase after active treatment

• Randomized, placebo, controlled trial

• Daily hot flash diary

By week eight, SA produced significantly greater reduction in HFCS than did PP (-2.39; 95% CI [-4.6, -0.17]). Among all treatment groups, the mean reduction of HFCS was greater in the EA group, followed by SA, GP, and PP (-7.4 vs -5.9 vs -5.2 vs -3.4; p = < 0.001). The pill groups had more treatment-related adverse effects than did the acupuncture groups; GP (39.3%), PP (20%), EA (16.7%), and SA (3.1 %), with p = 0.005. By week 24, HFCS reduction was greatest in the EA group, followed by SA, PP, and GP (-8.5 vs -6 vs -4.6 vs -2.8; p = 0.002).

EA resulted in the greatest reduction in hot flashes both at the end of the treatment and four months after the treatment. GP had similar effects while women received treatment, but not off treatment. Acupuncture (both SA and EA) elicited greater placebo and smaller nocebo effects than did GP or PPs for the management of hot flashes.

• Intervention expensive, impractical, or training needs
• The training required to accurately administer EA is of concern and was not thoroughly addressed.
• The sample size was small for a four-group study.

The EA group was found to have enhanced effects of reducing hot flashes in breast cancer survivors; however, SA also had better effects in reducing hot flashes than either GP or PPs. GP was associated with the most adverse effects, and the PP group reported more nocebo effects than did SA. This might be important information for nurses to be aware of as they provide education to patients.

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.

• N = 67 (159 were screened; 76 were enrolled; 9 were excluded during the next round of evaluations; 4 were lost to follow-up by time 2 [4 weeks] and 4 more were lost to follow-up by time 3 [12 weeks])  
• MEAN AGE: 59.7 years (range = 41–76 years)
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: Breast cancer survivors being treated with aromatase inhibitors (AIs) for 3–56 months. 66% of participants were being treated with an AI at the time of the study. At baseline, there were significant correlations between baseline pain (as measured by the Brief Pain Inventory) and fatigue, sleep, and depression, but there was no correlation with anxiety. Most participants (71.6%) were white and 23.9% were black; greater than 75% reported college education. Disease: 48%–50% were at disease stage I, 30–36 % were at disease stage II, and 14%–22 % were at disease stage III.  
• OTHER KEY SAMPLE CHARACTERISTICS: Most participants (71.6%) were white and 23.9% were black; greater than 75% held some college education. Inclusion criteria: Women with histories of stages I–III breast cancer currently taking an AI, current complaints of joint pain times three months, attributes pain to AI, current-week pain rating of 4 or greater on an 11-point rating (0–10), complaints of pain at least 15 days within the last 30 days. 

• SITE: Single-site    
• SETTING TYPE: Not specified    
• LOCATION: The Abramson Cancer Center of the Hospital of the University of Pennsylvania

• PHASE OF CARE: Active antitumor treatment
• APPLICATIONS:  Elder care, palliative care 

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.

• Small sample (< 100)
• Risk of bias (no blinding). There was no blinding but the risk of bias is low because each arm of the study required specific treatment limited to administration by just two acupuncturists.

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.

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.

• N = 36
• MEAN AGE = 59.67 years
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: All received aromatase inhibitors ranging from 19.5–31.1 months across groups. Duration of joint pain ranged from 43.4–62.9 on average. Duration was highly variable across groups.

• SITE: Single site 
• SETTING TYPE: Outpatient 
• LOCATION: Pennsylvania

• PHASE OF CARE: Active antitumor treatment

• Double-blind, placebo-controlled RCT

• Brief Pain Inventory (BPI)
• Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)
• Quick Disability of Arm Shoulder Hand (DASH)
• Physical Performance Test (PPT)

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.

• Small sample (less than 100)
• Subject withdrawals 10% ore more
• No information is provided regarding pain medication use.
• Withdrawals were high, suggesting that the intervention may not be acceptable or practical for many patients.

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.

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.