To review the evidence regarding the effects of Chinese herbal medicine on side effects of chemotherapy in women with breast cancer.

Databases searched were Cochrane Library, EMBASE, LILACS, SIGLE, and Chinese Biomedical Disk. Handsearching of key medical journals and references lists of retrieved articles was also performed.

Search keywords were Chinese medicine, plants, drugs, botanical, herbal medicine, and additional search terms related to herbal medicine as well as breast cancer treatments. A full listing of search terms was provided.

Studies were included if they included

• Women with breast cancer receiving chemotherapy as adjuvant or palliative treatment. 
• Single and compound herbal treatments. 
• Randomized clinical trials with chemotherapy-induced side effects.

Patients were excluded if they had other cancers as well as breast cancer (except for skin cancer).

In total, 88 references were retrieved. The authors allocated trials to quality categories described in the Cochrane Reviewers' Handbook and assessed quality according to criteria from Schultz (1995); studies were categorized as having a low, moderate, or high risk of bias.

• The final number of studies included was seven.  
• The sample range across studies was 48 to 120 patients (N = 541).
• All patients had breast cancer and were receiving chemotherapy. 
• All studies were performed on Chinese patients in a mix of settings.

Patients were undergoing multiple phases of care.

Trial duration ranged from 14 to 84 days. Treatments were varied with different herbal concoctions; most included radix ginseng along with other substances. The authors did not provide the findings for all outcomes of interest. A few studies measured quality of life, and several attempted to evaluate the effect on thrombocytopenia and white blood cell volumes and types. Some studies used inappropriate statistical methods. The quality of the included trials was poor.

The nature of the evidence in use of Chinese herbal medicine was not sufficient to draw any conclusions.

The study included a small number of studies with relatively small samples and poor quality.

The evidence reviewed did not provide clear implications for the incorporation of findings into practice. Further well-designed research is needed.

STUDY PURPOSE: To compare the effects of different regimens of NK₁-based antiemetic treatment for patients receiving highly emetogenic chemotherapy (HEC) or moderately emetogenic chemotherapy (MEC)

TYPE OF STUDY: Meta-analysis and systematic review

TOTAL REFERENCES RETRIEVED: 1,796

• FINAL NUMBER STUDIES INCLUDED = 35 
• TOTAL PATIENTS INCLUDED IN REVIEW = 18, 889
• SAMPLE RANGE ACROSS STUDIES: 16–1438
• KEY SAMPLE CHARACTERISTICS: All were receiving moderately emetogenic chemotherapy (MEC) or highly emetogenic chemotherapy (HEC) treatment regimens.

PHASE OF CARE: Active antitumor treatment

Regimens using various NK₁s showed equivalent antiemetic effect in the overall, acute, and delayed phases. In patients receiving HEC, almost all triple-drug regimens showed significantly higher complete response rates when compared to duplex antiemetic regimens. In patients with MEC, the only NK₁ that showed better antiemetic effect than duplex regimens was aprepitant. Palonosetron-based regimens did not show any difference from first generation 5-HT₃s for CINV complete response rate. No differences in outcomes were observed with differing doses of dexamethasone as part of a triple-drug regimen.

This analysis provides some key information regarding the specific selection of agents and regimens used for CINV control among patients receiving MEC and HEC. Consistent with other evidence, CINV was best controlled with a triple-drug regimen rather than a duplex regimen. The findings suggest that varied doses of dexamethasone do not reduce efficacy.

No quality evaluation

The findings suggest that a standard triple drug regimen is more effective for CINV control with HEC regimens compared to duplex regimens. The findings also suggest that differences in dexamethasone dosing does not appear to alter antiemetic effectiveness. Regimens with reduced use of corticosteroid may be needed for patients with diabetes or low tolerance for side effects of steroids.

To evaluate transcutaneous electroacupuncture (TEA) on chemotherapy-induced nausea and vomiting (CINV) as well as serotonin and dopamine levels among patients with cancer

• N = 72
• AGE = Not stated
• MALES: 60% (43), FEMALES: 40% (29)
• KEY DISEASE CHARACTERISTICS: Not stated
• OTHER KEY SAMPLE CHARACTERISTICS: All were naïve to chemotherapy or received only moderate to highly emetogenic chemotherapy; scheduled to receive moderate or highly emetogenic chemotherapy (cisplatin > 50 mg/m², cyclophosphamide > 1,500 mg/m², or carmustine > 250 mg/m²)

• SITE: Single site
• SETTING TYPE: Inpatient
• LOCATION: Zhejiang Provincial Hospital of Traditional Chinese Medicine

• PHASE OF CARE: Active antitumor treatment

Randomized, controlled trial

• Nausea and vomiting: Patients recorded the date and time of emesis or retching, the degree of nausea (none, mild, moderate, or severe), and the use of rescue medications (name, dose, and time) in a diary.
• Serotonin and dopamine
• Safety measures: Vital signs, 12-lead electrocardiogram (EKG), blood tests (white blood cell count, aspartate transaminase, alanine transaminase, and creatinine clearance), and urinalysis

Vomiting was significantly improved in the treatment group compared to the control group at 48 hours only (p = 0.046). No difference was noted at 24 hours (p = 0.9) or 72 hours (p = 0.68). Nausea was significantly better for the treatment group than the control group at 48 hours (p = 0.001) and 72 hours (p = 0.025) but not at 24 hours. Serotonin and dopamine were not different at baseline but were significantly reduced in the treatment group when compared to the control group at 48 hours (p = 0.03) and 72 hours (p = 0.02). No safety issues were noted in any patients. Laboratory results and EKG tests were normal.

Transcutaneous electroacupuncture was effective at improving delayed nausea and vomiting and had no significant safety issues.

• Small sample (< 100)
• Other limitations/explanation: Sample characteristics were not adequately reported, and no differences between the groups were noted. The authors did not report if any subjects withdrew from the study.

The needleless system of transcutaneous electroacupuncture made administration easy and compliance rates high.

To test the effects of a nurse-led, self-efficacy-enhancing intervention for patients with colorectal cancer compared to routine care over a six-month follow-up period

Verbal and written information on self-efficacy and techniques to increase self-efficacy were distributed, and 20–40 minute coaching follow-up sessions were conducted via telephone. The control group received routine care, which included information provided by the nurse on knowledge of chemotherapy and side effects before patients started treatment (about 30 minutes). The intervention was based on Bandura’s (1977, 1986) self-efficacy theory. The self-efficacy intervention was complex and included an hour-long, face-to-face education session conducted by an oncology nurse, an educational handbook that contained information on the core components of self-efficacy, a 30-minute audiotape on relaxation, and four monthly health-coaching telephone follow-up sessions (20–30 minutes each) with an oncology nurse.

• N = 121  
• MEAN AGE = 53 years (SD = 11.3 years)
• MALES: 64.5%, FEMALES: 35.5%
• KEY DISEASE CHARACTERISTICS: Colorectal cancer
• OTHER KEY SAMPLE CHARACTERISTICS: Adult Chinese patients diagnosed within the past six months; access to a telephone; could understand and communicate in Chinese; at least 18 years old; patients understood they were diagnosed with cancer and were scheduled to receive chemotherapy after cancer-related surgery

• SITE: Multi-site    
• SETTING TYPE: Multiple settings    
• LOCATION: Asia

Randomized, controlled trial with repeated measures and a two-group design

• Self-efficacy was assessed using the Stanford Inventory of Cancer Patient Adjustment (SICPA).
• Symptom distress was evaluated using the Chinese version of the MD Anderson symptom Inventory (MDASI).
• Anxiety and depression were measured using the Chinese version of the Hospital Anxiety and Depression Scale (HADS).
• Quality of life was measured using the Functional Assessment of Cancer Treatment–General (FACT-G).

The intervention group experienced a significant improvement in self-efficacy (f = 7.26, p = .003), a reduction in symptom severity (f = 5.30, p = .01), symptom interference (f = 4.06, p = .025), anxiety (f = 6.04, p = .006), and depression (f = 6.96, p = .003) at three and six months compared to the control group. No statistically-significant main effect was observed in quality of life perception between the two groups.

A nurse-led, self-efficacy-enhancing intervention was effective in promoting self-efficacy and psychological well being for three and six months compared to the control group. The findings of this study suggest that the intervention is feasible, and improvements could be sustained for six months after the intervention.

• Risk of bias (no blinding)
• Findings not generalizable
• Other limitations/explanation: Conducted in one cancer center and two affiliated hospitals in southern China; findings might not reflect situations of patients living in other areas of China; only monitored patients up to six months

Self-efficacy-enhancing interventions that are lead by nurses may improve the psychological well-being of patients with colorectal cancer.

PHASE OF CARE: Active antitumor treatment

The meta-analysis supported the efficacy of mindfulness-based therapies in the improvement of anxiety and depression levels for people with cancer. The authors note that previous meta-analysis of MBSR studies included only 2 of 9 studies that were RCTs. All seven studies included in this analysis were RCTs. MBSR and mindfulness-based art therapy were the most frequently used mindfulness therapies (5 of 7), and all studies reported anxiety and depression scores. Subgroup analysis of the data further supported the effectiveness of mindfulness-based intervention in relieving anxiety and depression across cancer type and stage.

• Lack of consistency in type of mindfulness-based intervention between studies.
• The subgroup analysis indicated that some interventions may be more effective in specific cancer types.
• None of the studies in the this meta-analysis indicated where participants were receiving concurrent medical or somatic treatment for anxiety or depression at the same time as the mindfulness-based interventions.  
• Small number of studies and different forms of cancer in the studies

This meta-analysis supports the effectiveness of mindfulness-based interventions for management of cancer-related anxiety and depression.

STUDY PURPOSE: To evaluate the effects of yoga in women with breast cancer

TYPE OF STUDY: Meta-analysis and systematic review

DATABASES USED: PubMed, EMBASE, Cochrane Library, Chinese Biomedical Literature Database, and Chinese Digital Journals Database

KEYWORDS: Yoga or asana and breast cancer, and additional breast cancer terms

INCLUSION CRITERIA: Randomized controlled trial (RCT) comparing yoga or yoga-based intervention with a control group

EXCLUSION CRITERIA: Studies that included yoga as part of a larger intervention

TOTAL REFERENCES RETRIEVED: N = 86

EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Cochrane handbook was used for evaluation of methodological quality. Randomization was unclear in all but one study, and only one study blinded investigators. Three studies did not report complete outcome data, and dropouts were substantial percentages of the sample in all studies

• FINAL NUMBER STUDIES INCLUDED: N = 6 included in meta-analysis  
• SAMPLE RANGE ACROSS STUDIES: Range = 18-164
• TOTAL PATIENTS INCLUDED IN REVIEW: N = 382
• KEY SAMPLE CHARACTERISTICS: All were women with breast cancer aged ≥ 30 years.

Anxiety was measured in two studies, and meta-analysis showed no significant effect. Depression was measured in two studies, and meta-analysis showed no significant effect of yoga on depression. Fatigue was examined in five studies with no significant effect shown in meta-analysis. Sleep was measured in two studies with no significant effect shown in meta-analysis. Overall, quality of life was the only outcome measure in which a significant effect was seen from meta-analysis (SMD = 0.27, p = .03).

Insufficient evidence exists to advocate for the use of yoga in patients with breast cancer. No significant effects were seen related to anxiety, depression, sleep disturbance, or fatigue in these patients.

A small number of studies were included, and all had methodological limitations. Yoga interventions differed and varied in frequency and duration.

Insufficient evidence exists to show a benefit of yoga for women with breast cancer. High quality research is needed to evaluate the effects of yoga for symptom management.

STUDY PURPOSE: To identify the relative value of current approved medications for breakthrough pain

TYPE OF STUDY: Meta-analysis and systematic review

• FINAL NUMBER STUDIES INCLUDED = 10
• TOTAL PATIENTS INCLUDED IN REVIEW = 892
• SAMPLE RANGE ACROSS STUDIES: 66–139 patients
• KEY SAMPLE CHARACTERISTICS: None specified

APPLICATIONS: Palliative care

Intranasal fentanyl spray (INFS), fentanyl pectin nasal spray, fentanyl buccal soluble film, fentanyl sublingual tablets, fentanyl buccal tablets, oral transmucosal fentanyl citrate, and immediate-release morphine sulfate were all superior to a placebo. All medications other than morphine sulfate were superior at 15 minutes, and INFS provided the greatest effect in this timeframe. There was evidence that INFS was most effective compared to others at five minutes. However, these data were of lower quality. Overall, the studies were of high quality.

All of the current approved medications for breakthrough pain were effective. Transmucosal agents and INFS were effective more quickly than immediate-release oral morphine.

None identified

The findings of this meta-analysis suggest that transmucosal and intranasal medication for breakthrough pain are effective more rapidly than immediate-release oral morphine. These should be considered for the management of breakthrough pain, according to patient tolerance and preferences. INFS could be considered the treatment of choice for patients with rapid-onset and short-duration breakthrough pain.

To explore and assess evidence regarding the use of opioids in the management of breakthrough pain in patients with cancer

Databases searched were Cochrane Pain, Palliative & Supportive Care Register, Cochrane Controlled Trials Register, MEDLINE, EMBASE, CANCERLIT, Science Citation Index, CINAHL, System for Information on Grey Literature in Europe (SIGLE), LILACS, and databases related to these journals: European Journal of Palliative Care, International Journal of Palliative Nursing, Progress in Palliative Care, The Hospice Journal, Journal of Palliative Medicine, and American Journal of Hospice and Palliative Care.

Authors analyzed four randomized controlled trials that involved opioids used as rescue medication. Each trial compared the action of an opiod to an active or placebo comparator in patients with cancer pain. All studies were conducted in an outpatient setting in the United States. In each study, oral transmucosal fentanyl citrate (OTFC) was the subject of the investigation.Two studies examined dose titration of OTFC, one study compared OTFC to placebo, and one study compared OTFC to normal-release morphine. All studies were divided into two phases.

In the two studies assessing the effectiveness of OTFC, investigators evaluated the performance of the rescue drug in phase 1. In phase 2, participants were randomized to two groups: one started drug therapy at 200 mcg OFTC; the other, at 400 mcg OTFC. Clinicians titrated to the effective dose and then evaluated the performance of the drug. 

In the study assessing OTFC to placebo, in phase 1 drug therapy started at 200 mcg OTFC and the dose was titrated for effective relief. After adequate pain control, patients entered phase 2 and received OTFC equal to the amount effective in phase 1 plus placebo.

In fourth study, which compared OTFC with normal-release morphine, participants started drug therapy at 200 mcg OTFC and titrated up for effective pain relief. Once obtaining effective pain relief, participants entered phase 2, where they received equal amounts of OTFC versus their pretrial dose of normal-release morphine.

All studies recruited adults who experienced at least one episode but no more than four episodes of breakthrough pain daily. Each participant was taking a stable dose of opioid that consisted of either an oral opioid (at least the equivalent of 60 mg oral morphine per day) or transdermal opioid (at least 50 mcg/hour transdermal fentanyl). Two studies recruited 129 patients and identified the dose of OTFC adequate to treat one episode of breakthrough pain. One study of 130 participants compared OTFC to placebo. Another study, with 134 participants, compared OTFC and normal-release morphine. Across all four studies the sample consisted of 393 participants.

The studies identified in this review were specific to the use of OTFC for breakthrough pain in patients with cancer. All studies included similar outcome measures and were of high quality. This review shows that, compared to usual rescue medication or placebo, OTFC is an effective treatment for breakthrough cancer pain and is associated with a greater analgesic effect, better satisfaction, and a more rapid onset.

The evidence base relates to OTFC only. An increasing number of opioids are in use; these opioids (morphine, oxycodone, hydromorphone, and oxycodone) should be studied and compared in regard to effectiveness in the treatment of breakthrough pain. Such studies should be performed using the OTFC template.

Nebulized morphine 20 mg mixed with 2 mL of saline was administered using a face mask every four hours for 48 hours.

• The sample was comprised of 17 patients in hospice care with nonreversible dyspnea, either at rest or on exertion, associated with primary or secondary malignant intrathoracic disease; six patients also had chronic obstructive pulmonary disease (COPD).
• Mean age was 68 years.
• Of the patients, 12 (71%) were male.
• Thirteen patients were already taking opioids.
• Fourteen patients completed the trial.

Unknown but assumed to be in a hospital

The study used an open, uncontrolled, nonrandomized design.

The Dyspnea Assessment Questionnaire (DAQ) and a recalled 24-hour visual analog scale (VAS) were used. Three subscales of the DAQ—Total Severity Score, Percentage Total Severity Score (PTSS), and Dyspnea Quality-Quantity Score (DQQS)—were also analyzed. DQQS was the primary outcome measure. Measurements were taken at baseline (one hour before the first dose of nebulized medication) and were repeated at 24 and 48 hours.

Sixteen patients (94%) reported significantly lower (p = 0.0005) DQQS scores at 24 hours. The four opioid-naïve patients showed no significant benefit from the nebulized treatment. (The theory is that the prevalence of binding receptors in airways is influenced by systemic use of opioids.) Improvement appeared greater in the qualitative aspect of dyspnea as shown by PTTS versus VAS. Benefits were noted at 24 hours and did not improve from there. Change in DQQS scores from 24 to 48 hours was not significant (p-value not given).

Qualitative aspects of dyspnea improved more than quantitative aspects.

• The study had a small sample size.
• Due to the uncontrolled nature of the study, the placebo effect cannot be ruled out.
• One patient refused to participate after the first dose, reporting claustrophobia.
• Fourteen patients completed the trial. Three patients dropped out after 24 hours (two because of a dislike for the nebulizer and one because of weakness); otherwise, no significant side effects were reported.
• Six patients who discontinued nebulized treatments after 24 hours did so because of weakness. Weakness appeared to reduce the acceptability of the nebulized intervention.

STUDY PURPOSE: To examine the effects of cognitive training and cognitive rehabilitation interventions on cognitive function in adults with non-central nervous system cancers

TYPE OF STUDY: Meta-analysis and systematic review

• FINAL NUMBER STUDIES INCLUDED = 9 included in the meta-analysis
• TOTAL PATIENTS INCLUDED IN REVIEW = 410 included in the meta-analysis
• SAMPLE RANGE ACROSS STUDIES: 22–98 patients 
• KEY SAMPLE CHARACTERISTICS: The mean age in studies ranged from 45–75 years. Cancer diagnoses were breast (n = 4) or mixed non-CNS (n = 5) cancers. Two studies were not randomized. Five studies had sample sizes of less than 40.

PHASE OF CARE: Multiple phases of care
 
APPLICATIONS: Elder care

Three studies tested cognitive training, and six studies tested cognitive rehabilitation. Most studies used waitlist control groups, with intervention durations of one to six months. Outcomes included verbal and/or visual memory (n = 8), executive function (n = 4), attention (n = 6), processing speed (n = 2), language (n = 1), and self-reported cognitive function (n = 9). A moderate-to-high risk of bias was found across studies. Statistical heterogeneity ranged from 0% to 96%. By outcome measure, the number of studies included in each part of the meta-analysis ranged from two to five. Cognitive training and cognitive rehabilitation interventions improved immediate (n = 2, WMD = 7.58, 95% confidence interval [CI] = [0.07, 15.09], p < 0.05) and delayed (n = 2, WMD = 10.85, 95% CI [4.19, 17.51], p = 0.001) memory at post intervention. Both types of interventions improved verbal learning at post intervention (n = 5, SMD = 0.5, 95% CI [0.19, 0.81], p = 0.001) and follow-up (n = 3, SMD = 0.58, 95% CI [0.19, 0.98], p = 0.004). Cognitive training interventions improved self-reported cognitive function at post intervention (n = 2, SMD = 0.52, 95% CI [0.06, 0.98], p = 0.03) and follow-up (n = 2, SMD = 0.54, 95% CI [0.08, 1], p = 0.02).

The meta-analysis indicated that both cognitive training and cognitive rehabilitation interventions may improve objectively measured memory and verbal learning, whereas cognitive training interventions may improve self-reported cognitive function. No treatment effects were found for executive function, attention, processing speed, or language. The weaknesses of this meta-analysis limit its usefulness in determining the effects of these types of interventions on cognitive function.

• Limited number of studies included
• High heterogeneity
• Low sample sizes

Individual-based cognitive training and group-based cognitive rehabilitation may improve objectively measured memory and verbal learning, as well as self-reported cognitive function, in adult survivors of cancer. Because of the small number and weaknesses of included studies, the benefits of these interventions are unclear.