STUDY PURPOSE: To summarize the results from randomized, controlled trials (RCTs) of the effectiveness of Chinese herbal medicines (CHMs) for managing fatigue, paresthesias, chronic pain, anorexia, edema, and constipation

TYPE OF STUDY: Meta-analysis and systematic review

• FINAL NUMBER STUDIES INCLUDED = 14 
• TOTAL PATIENTS INCLUDED IN REVIEW = 878
• SAMPLE RANGE ACROSS STUDIES: 35–124 patients
• KEY SAMPLE CHARACTERISTICS: Various cancer sites

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

• Fatigue—four RCTs. In three RCTs, no difference existed between CHM and chemotherapy versus chemotherapy alone. In the other RCT, Fu Zheng decoction plus chemotherapy (ellence [epirubicin]/paclitaxel [taxol]) improved fatigue score compared to chemotherapy alone in breast cancer (MD: –18.62, 95% CI [–24.18, –13.16]).
• Pain—three RCTs. CHM plus conventional treatment decreased the pain score compared to conventional treatment alone (WMD: –0.9, 95% CI [–1.69, –0.11]).
• Constipation—seven RCTs. In six RCTs, CHM compared to conventional treatment had a similar effect. In the other RCT, Tong-Tai decoction plus chemotherapy compared to chemotherapy alone showed no difference.
• Anorexia—two RCTs. No difference existed with CHM plus conventional treatment.

Combining CHM with chemotherapy may improve fatigue in patients with breast cancer. Adding CHM to conventional treatment may improve pain control. CHM alone may improve constipation.

• Mostly low quality/high risk of bias studies
• High heterogeneity
• Trials conducted and published in China

Further research needs to be performed on CHM treating cancer- and cancer treatment-related symptoms.

The physical, psychological, physiologic, and behavioral aspects of the patients included in most of the studies were changed significantly by the exercise interventions. Physiotherapy improved range of motion, shoulder function, and pain, regardless of the intervention dosages. The effect of the interventions on lymphedema wasn’t apparent at six months but was visible at 12 months’ follow-up. Eight weeks of aerobic exercise was effective for psychological and behavioral outcomes through 24 weeks postintervention, but no significant long-term physical health effects were apparent. Aqualymphatic therapy affected emotional and social quality of life (QOL) but not physical QOL or limb volume. Dance and movement was not effective for lymphedema or health-related QOL. It only was effective for breast cancer-related QOL. Home-based rehabilitation improved some range of motion but did not affect pain, lymphedema, or strength.

Physical therapy is beneficial for shoulder range of motion when implemented soon after surgery. Any type of structured exercise could improve shoulder mobility, range of motion, and shoulder function in a relatively short period of time. The long-term effects of physiotherapy need to be studied more extensively. Multimodal exercise and comprehensive rehabilitation, including physical therapy, had physical and psychological effects. Aerobic exercise and dance and movement had a positive psychological effect. Exercise is essential to lymphedema treatment and management.

Few of the studies included long-term follow-up to measure the effects of the interventions on lymphedema development and severity.

Informing patients with breast cancer about the importance of exercise after receiving surgery and teaching patients ways to decrease the limitations that may occur after surgery is necessary.

The intervention was a six-week structured psychosocial support group of 90 minutes led by a male psychiatrist and nurses with experience in facilitation cancer groups. Each group member received

• 20 minutes for stress-management method and problem-solving method
• 50 minutes for discussion on coping
• 20 minutes for learning progressive muscle relaxation (PMR) and audiotapes to use twice a day.

Measurements were done at baseline, then immediately following the six-week intervention, then three months and six months later.

Eleven women refused to participate but were interested in group intervention and consented to answering questionnaires. These women were given materials after completion of the survey and the PMR tape.

• The participants were Japanese women with first recurrence of breast cancer (recurrence within three months to one year of initial diagnosis).
• The intervention group consisted of 28 participants (19 finished the trial); 11 women refused to participate.

The study design was quasi-experimental without a control group.

• Profile of Mood States (POMS)
• Impact of Event Scale–Revised
• Mental Adjustment to Cancer Scale
• EORTC Quality of Life Questionnaire—Cancer 30/Breast module 23 (QLQ-C30/Br23)
• Dunnett’s test to examine changes in scores between baseline and at three and six months after the intervention

Results in the intervention group revealed significant changes in scores for tension-anxiety on POMS in the period up to three months after the intervention; no differences were noted at six months after the intervention.

• The study had a nonrandomized design.
• The study had a small sample size.

To determine the effects of music therapy on subjective sensations and physiologic parameters of heart rate variability (HRV) in treated cancer survivors.The hypothesis was that music therapy significantly affects the sensations of fatigue, comfort, and relaxation, as well as the activities of the sympathetic and parasympathetic nervous systems.

Participants were asked to sit and rest for five minutes to stabilize their heart and respiration rates when they first arrived in the group therapy room. An electrocardiogram (ECG) signal then was measured for five minutes, and fatigue, comfort, and relaxation were rated subjectively on the visual analog mood scales (VAMS) as a pretest. After participating in two hours of music therapy, the same procedure was performed again as a posttest.  

The two-hour music therapy intervention consisted of three activities. In the first activity, the program aimed at establishing a rapport between therapists and participants through singing and listening. The song for the first activity was a popular Taiwanese song called ‘‘He is Our Treasure,’’ which had pleasant moderate rhythm and tempo. The second activity was to learn how to play the recorder. This activity used simple musical instrument learning to establish the participants’ self-confidence. The third activity was to perform the main five notes of a familiar melody song, ‘‘Grandfather’s Clock,’’ following the therapist’s electric keyboard accompaniment and conduct. This activity sought to encourage the participants to express themselves through playing the recorder and to create light and joyful emotions.

• The sample was comprised of 23 women with cancer (breast [n = 19], ovary [n = 2], cervical [n = 1], and bone [n = 1]).   
• Mean age was 49.9 years (standard deviation = 9.2 years) (range 30–67).
• Participants were recruited from the Hope Society for Cancer Care in Taipei, Taiwan.

• Single site
• Outpatient
• Taiwan

• Patients were undergoing the posttreatment phase of care.
• The study has clinical applicability for late effects and survivorship.

The study used a pre-/posttest, quasiexperimental design.

• ECG monitoring    
• VAMS
• HRV monitor
• The study assessed whether participants were fatigued, comfortable, and relaxed, but no questionnaire was described.
   

Comparison of the quantitative HRV measures at pre- and posttest revealed that the high frequency (HF) power and normalized HF power were significantly higher, and the low frequency (LF)/HF ratio and normalized LF power of HRV were significantly lower at posttest than at pretest (p < 0.05). The VAMS mean value for the fatigue level was significant lower after music therapy (p < 0.05). The VAMS mean value for relaxation level was significant higher after music therapy (p < 0.05).

In a small sample size including varied cancer diagnoses with limited information about the study participants, the assessment showed changes in fatigue, relaxation, comfort, and HRV.

• The study had a very small sample, with less than 30 participants.
• The study lacked a control group.
• The study included various cancer diagnoses.
• The study used a cross-sectional design.
• Symptom instruments were not multidimensional or psychometrically tested, and no description was given for how the symptom questions were presented to the participants.   

Additional research is needed, including the use of psychometrically tested symptom instruments. Based on the descriptive findings in this very small initial study evaluating HRV, fatigue, and relaxation, it may not be appropriate to include it in PEP topic research. This study was completed by colleagues in a biomedical engineering school. Describing the process of how this was accomplished (e.g., surveys with nurses assisting) might be useful.

To assess the benefits of standard physical therapy (PT) compared to PT with manual lymph drainage (MLD) on lymphedema incidence, shoulder function, pain, and cording in patients with breast cancer with axillary web syndrome (AWS)

• Participants were divided into one of two groups: Participants in group 1 (n = 20) received PT (three times per week for four weeks). Participants in group 2 (n = 21) received PT combined with MLD (five times a week for four weeks), where participants independently performed MLD therapy on their own when not at rehab. All outpatient visits were supervised. All participants were prescribed nonsteroidal anti-inflammatories twice a day.  
• Exercise interventions included 10-minute warm up and 10-minute cool down stretches.  
• Upper extremity strength: Three different pulley exercises (3 sets of 10 repetitions)
• Shoulder flexion, abduction, and elbow flexion strength exercise: Theraband (3 sets of 10 repetitions)  
• MLD: 30 minutes of tissue mobilization of tight tissues of the chest wall, and antecubital fossa with full-hand or two-finger contact. Longitudinal tissue stretches of the cords with the arm in abduction, followed by scapular mobilization

• N = 41   
• AGE = 46.6 years (group 1), 50.7 years (group 2)
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: Patients with breast cancer with postoperative palpable and visible axillary cording in the axilla and the arm, pain rated greater than 3 on a numeric rating scale (NRS)

• SITE: Single site   
• SETTING TYPE: Outpatient    
• LOCATION: South Korea

PHASE OF CARE: Late effects and survivorship

This was a prospective, randomized trial of patients with breast cancer who had undergone surgery and were randomized to two therapy interventions.

• Participants were measured at the start of therapy and again at the end of therapy. The therapist who performed the measurements was blinded to the study groups. 
• Arm volume was measured using a measuring tape. Circumference measurements were taken at 4-cm intervals from the wrist to the axilla, with which volume was calculated.
• Muscular strength: Handheld Dynameter measured three times the average used for shoulder flexion and abduction, elbow flexion
• Active ROM (AROM) measured with a digital inclinometer in the shoulder positions supine flexion and supine abduction; each were performed three times, and the averages were used.
• Quality of life: The European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30), 30 questions with five functional and three symptom areas; the EORTC QLQ-BC, 23 questions, either functional or symptom
• Visible and palpable cording in the arm and the axilla: The presence or absence of the authors' recording was determined by the rehabilitation physician.  
• Arm disability: The 30-item Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire, which is not breast cancer specific, was used to assess upper limb function. High scores indicate greater disability.
• Pain: Patients rated their pain on a scale of 0–10 when performing shoulder abduction.

• Quality of life based on the two questionnaires (EORTC QLQ-C and EORTC QLQ-BC) showed significant improvement in both the physical therapy group and the physical therapy combined with MLD group (p > 0.05).  
• Shoulder flexor strength, shoulder flexion, and abduction range of motion (ROM) improved; DASH score and pain NRS score also improved in both groups (p > 0.05). NRS scores decreased more in the PT and MLD group (p > 0.05). Visible cording: 28.5% continued in the PT and MLD group and 35% in the PT only group.  
• Arm volume significantly increased in the physical therapy group (p > 0.05). Six patients developed lymphedema, which was verified with a lymphoscintigraphy. The typical incidence range of lymphedema is 13%–65%. In this study, 33.3% developed lymphedema. 
• Overall significant changes occurred in all areas in both groups but not between groups except for the PT and MLD group, which did not experience any volume increase. A significant increase of lymphedema was seen in the PT group.

All patients benefited from postoperative PT, but patients who had PT and MLD did not develop lymphedema. Measurements were not taken weekly, so when the changes in arm volume occurred cannot be identified. This study supports wearing compression during therapy. Patients are at risk for lymphedema even when engaging in supervised exercise.

• Small sample (< 100)
• As stated by the authors, a control group would have allowed an observation of the natural course of AWS. NSAIDs were prescribed, but their use was not monitored. Also, patients were not told to perform or not perform exercises on their own. Perhaps the patients with lymphedema were performing more exercises.

Nurses need to vigilantly monitor for symptoms of pain in the ipsilateral limbs of patients with breast cancer to prevent loss of function, chronic pain, and lymphedema. As seen in this study, even pain at level 3 is significant. Patients need early PT referral to prevent arm disability and early lymphedema therapy.

To compare the efficacy of dexamethasone to placebo for prevention of pain flare after palliative radiotherapy

Patients were randomized to receive either 8 mg dexamethasone or placebo at least one hour before the start of radiotherapy and then daily while receiving radiotherapy. Patients completed study assessments at baseline, day 10, and day 42 after radiation treatment.

• N = 298   
• MEDIAN AGE = 69 years
• AGE RANGE = 58–77 years
• MALES: 57%, FEMALES: 43%
• CURRENT TREATMENT: Radiation
• KEY DISEASE CHARACTERISTICS: Multiple tumor types—breast, prostate, and lung were predominant. Single dose of 8 Gy was used to target volumes planned.
• OTHER KEY SAMPLE CHARACTERISTICS: Of the patients, 50% had worst pain at baseline between 7–10 on the numeric scale.

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

• PHASE OF CARE: Late effects and survivorship
• APPLICATIONS: Elder care, palliative care 

• Double-blind, placebo-controlled

• Brief Pain Inventory (BPI)
• Daily pain diary with numeric scale
• EORTC QLQ-C15-PAL for palliative, EORTC QLQ-C30 for quality of life, and EORTC QLQ-BM22 for bone metastases
• Dexamethasone Symptom Questionnaire (DSQ)

Median follow-up ranged from 1-39 months. Ninety-two patients experienced pain flare on days 0–10, 26% in the dexamethasone group and 35% in the placebo group (p = 0.05). The incidence of pain flare was 11.8% lower in the dexamethasone group (p = 0.01). No significant differences were noted between groups in overall pain reduction from radiotherapy or analgesic intake. Three patients on dexamethasone stopped the study medication due to hyperglycemic events. Two of these had preexisting diabetes.

Provision of 8 mg dexamethasone prior to and daily during palliative radiation therapy for bone metastases was effective in the prevention of radiation-associated pain flare compared to placebo.

• High variability in follow-up measurement time frames

This study showed that administration of dexamethasone during palliative radiation therapy for bone metastases was effective in preventing bone flare pain. A few patients developed hyperglycemic episodes while on dexamethasone, so nurses need to be aware of this potential, particularly in patients with preexisting diabetes. The purpose of palliative radiation is pain reduction, so it also makes sense to intervene to prevent pain flare that can occur from that treatment. Further research is warranted to compare prophylactic versus treatment of bone flare pain, and potential efficacy of other adjuvant medications.

To assess two different radiation therapy fractionation approaches in patients with painful bone metastases needing repeat radiation therapy

Patients with radiologically confirmed bone metastases that had previously been treated with radiation were randomized to receive 8 Gy in a single fraction or 20 Gy in multiple fractions. Those getting 20 Gy received treatment in five fractions unless the target field was the spine or whole pelvis. Bone-modifying agents and systemic therapy were allowed at the discretion of the physician. Overall response to treatment was the primary endpoint at two months after beginning treatment. Pain assessments were done at days 7 and 14, monthly for 6 months, and at 9 and 12 months after radiation therapy. A difference of 10% with treatment response was established to determine noninferiority.

• N = 521 per protocol (850 in intention-to-treat [ITT] analysis)
• MEAN AGE = 65 years
• MALES: 58.7%, FEMALES: 41.3%
• KEY DISEASE CHARACTERISTICS: Prostate, breast, and lung were the most frequent diagnoses. Other cancer types were included. 
• OTHER KEY SAMPLE CHARACTERISTICS: Average worst pain at baseline was 7–10. Baseline average morphine equivalent daily dose was 40–47.5 in the 20 Gy and 8 Gy groups, respectively.

• SITE: Multi-site  
• SETTING TYPE: Outpatient  
• LOCATION: International

• PHASE OF CARE: Late-effects, survivorship
• APPLICATIONS: Palliative care

Unblinded, randomized, controlled noninferiority trial

• Brief Pain Inventory (BPI)
• Complete response was defined as a worst pain score of 0 with no increase in daily morphine equivalent.
• Partial response was defined as pain with either a worst pain score reduction of at least two points and no increase in daily morphine equivalents or no increase in pain with a reduction of daily opioid consumption by at least 25%.
• Pain progression was defined as either an increase in worst pain score by two or more points with no change in opioid consumption or no change in worst pain score with increased opioid consumption.

In the ITT analysis, 28% in the 8 Gy group had response, and 32% of those in the 20 Gy group had overall response with a confidence interval that did not meet the noninferiority margin. In the per-protocol analysis, 45% of patients in the 8 Gy group and 51% in the 20 Gy group had overall response with a 95% confidence interval that met the 10% noninferiority margin. Patients in the 20 Gy group had more skin reddening and more frequent and severe anorexia, vomiting, and diarrhea (p < .05).

The per-protocol analysis showed that multiple fractionation was associated with slightly better pain response to treatment, but was also associated with more side effects.

• Unintended interventions or applicable interventions not described that would influence results
• Other limitations/explanation: Differences in use of bone-modifying agents are not reported in this manuscript. This study reports overall pain response but not complete or partial response data.

Radiation therapy to areas of painful bone metastases is effective in reducing pain. Though a higher total dose was slightly more effective, it was also associated with more side effects. Nurses can use this knowledge to educate patients and to monitor appropriate patients for treatment side effects.

STUDY PURPOSE: To summarize evidence from phase I and II trials in which olanzapine was used for the prophylaxis of chemotherapy-induced nausea and vomiting (CINV)

• FINAL NUMBER STUDIES INCLUDED = 7 
• TOTAL PATIENTS INCLUDED IN REVIEW = 201
• SAMPLE RANGE ACROSS STUDIES: 3–40 patients
• KEY SAMPLE CHARACTERISTICS: Multiple tumor types across studies; highly and moderately emetogenic chemotherapy regimens

PHASE OF CARE: Active antitumor treatment

The rate of complete control (no emesis, no rescue medication, and no significant nausea) was only identified in one study. Complete response rates were reported in three studies, and they ranged from 75%–100% in the acute phase and 72%–92.5% in the overall phase. In four trials, olanzapine was used as an adjunct with other antiemetics. One study was a retrospective chart review.

The findings of this study suggest that olanzapine can be beneficial in preventing CINV.

• The sample sizes of the studies were small.
• No information was provided regarding the use of any other antiemetics. 
• How a study using a retrospective chart review constitutes as a phase I or II study for inclusion was unclear.

The potential role of olanzapine in the prevention and management of CINV is unclear. This review provides limited evidence of the effects of olanzapine for CINV. Future studies need to compare olanzapine as an adjuvant to recommended antiemetics or olanzapine as a single agent compared to regimens with clear efficacy for the prevention of CINV.

To test the feasibility of the implementation of a psychoeducational intervention program for patients with gynecologic cancer

This study consisted of a series of interventions consisting of multiple components based on a thematic counseling model for patients with newly diagnosed gynecologic cancers. Blinding was performed at randomization. Quantitative data on sexual functioning, uncertainty, quality of life, anxiety, depression, and support systems were collected at recruitment, following surgery, during hospitalization, and eight weeks following surgery. Both quantitative and qualitative methods were used in the data analysis. The intervention consisted of four psychoeducational sessions. An individual format was used for the first three sessions and a group format was used for the last session. All intervention sessions were conducted by the researcher. The researcher also met with the control group on four occasions during the same period: at recruitment, after surgery, once in-hospital, and once via telephone four weeks following surgery during which participants were invited to attend a support group. The researcher was a registered nurse experienced in gynecologic cancer care.

• N = 26  
• MEAN AGE = 54.5 years
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: Cervical cancer, uterine cancer, and ovarian cancer
• OTHER KEY SAMPLE CHARACTERISTICS: Preoperative for surgical resection of disease

• SITE: Single-site    
• SETTING TYPE: Inpatient    
• LOCATION: Hong Kong

• PHASE OF CARE: Diagnostic
• APPLICATIONS: Elder care, palliative care 

Single-blinded, randomized trial with a mixed-methods design

• Baseline data on outcome variables were measured at the initial intervention for both groups. Both groups were reassessed following surgery, during inpatient stay, and eight weeks after surgery. A Sexual Function-Vaginal Changes Questionnaire (SVQ) was given during the third interview. Interviews were recorded.
• The Traditional Chinese Functional Assessment of Cancer Therapy–General (FACT-G) was used to measure quality of life. 
• Mishel’s Uncertainty in Illness Scale (MUIS) was used to measure perceived uncertainty.
• The Hospital Anxiety and Depression Scale (HADS) was used to assess anxiety and depression.
• The Medical Outcomes Study Support Survey (MOS-SS) was used to measure perceived social supports.
• Nonparametric inferential statistical methods were used in the analysis of quantitative data, including the Mann-Whitney U test and the Kruskal-Wallis test. Qualitative data were analyzed by content analysis based on transcriptions of the recordings.

Thirteen patients were in the intervention group and 13 were in the control group. There were no statistical differences between the populations of the two groups. The compliance rate was 69.2% in the intervention group with the greatest lack of compliance occurring during the final session. The compliance rate for the control group was 46.2%. Statistic significance regarding trends of change in the outcome variables was not obtained. There was no statistic significance in the comparison of baseline outcome variables of the two groups. There was no statistic significance of intervention effects between the two groups, except in the area of uncertainty. The inconsistency subscale showed a statistic significance between the two groups with the intervention group receiving less inconsistent information regarding their illnesses. The intervention group demonstrated better trends for improvement than the control group in all categories although there were contradictory results in the scales measuring quality of life, perceived social support, anxiety, and depression.

This patient population has healthcare needs that currently are not being met. This particular study did not show statistically significant results regarding anxiety, depression, quality of life, and sexual functioning in patients with gynecologic cancer. Further research is indicated.

• Small sample (< 30)
• Risk of bias (sample characteristics)
• Unintended interventions or applicable interventions not described that would influence results 
• Findings not generalizable
• Questionable protocol fidelity
• Other limitations/explanation: Three interventions took place during a relatively short period of time, and one took place two months later. The implementation period was six months long.

Further research is indicated regarding anxiety, depression, quality of life, and sexual functioning in patients with gynecologic cancer, particularly during the postoperative period. This study showed trends for overall improvement, indicating the importance of nursing in this population. Understanding the implications of cultural differences regarding the effects of gynecologic therapies is an important nursing responsibility.

To evaluate the use of electroacupuncture in preventing anthracycline-based chemotherapy-related nausea and vomiting (CINV) refractory to combination 5-HT₃-antagonist and dexamethasone

Patients received electroacupuncture in addition to standard antiemetic prophylaxis. Acupuncture was started 10 minutes prior to start of chemotherapy infusion and then continued for an additional 20 minutes. The P6 acupuncture point was used, a second needle was inserted at a different point, and electrical stimulation was delivered. 

• The study consisted of 27 patients with breast cancer.
• All patients were receiving their second cycles of doxorubicin and cyclophosphamide; cyclophosphamide, doxorubicin, and prednisone; or doxorubicin only.
• Patients were defined as having refractory emesis (defined as vomiting three or more times, 24-48 hours after cycle one).
• Patients received standard antemetic prophylaxis.

This was a prospective trial.

• Patients completed a questionnaire assessing their attitudes toward acupuncture. 
• Patients recorded frequency of vomiting in diaries.
• A trained doctor interviewed patients via telephone 24-48 hours after chemotherapy to grade nausea and vomiting using the National Cancer Institute Common Toxicity Criteria (NCI-CTC).

• Ten patients (37%) reported no vomiting after the second cycle of chemotherapy with the addition of electroacupuncture.
• The majority of patients (96%) reported significantly less nausea and vomiting, but one patient experienced increased vomiting after electroacupuncture.
• Overall, mean emetic episodes decreased from 7 to 3 after the intervention (p < 0.0001).
• NCI grade of vomiting decreased significantly (p = 0.0120).
• The number of patients reporting grade 3-4 vomiting dropped from 14 prior to the electroacupuncture to 5 after the electroacupuncture.
• NCI grade of nausea improved as well after the intervention (p < 0.0001).
• Most patients (93%) reported that they thought that electroacupuncture was an acceptable procedure and helpful in reducing emesis.

• All patients participated in the intervention group; no control group was provided.
• Two subjects complained of severe headaches after the electroacupuncture, lasting for several days; otherwise it was well-tolerated.
• The intervention was delivered by trained acupuncturists.