To evaluate the effect of indigowood root on acute mucositis induced by radiation

Patients gargled with 30 mL of double distilled water with 0.5g indigowood root (IR) powder for three minutes and then swallowed before meals daily. Control group did same with 30 mL of NS.

The study was comprised of 20 patients; tx group N = 11, control group N = 9

Age Information: IR group mean age was 56.45 (SD = 10.57).

Control group mean was 57.89 (SD+ 13.11) P = 0.789. There were two females in the IR group and 0 in the control group. There were nine males in the IR group and nine in the control group.

Diagnosis Information: Nasopharyngeal cancer

Oropharyngeal, salivary gland

Single site Outpatient Tian Sheng Memorial Hospital Taiwan

Randomized controlled trial

• NCI-CTC version 3
• Body weight
• Serum interleukin 1-beta; IL-6

IR group had reduced severity of mucositis (p = 0.01). anorexia (p = 0.002), and swallowing difficulty (p = 0.002). Serum interleukin-6 was significantly lower in the IR group during the first, fifth, and seventh weeks. Resting days were fewer in the IR group but not statistically significant; body weight decreased less in IR group (p = 0.06).

IR may be effective to reduce the severity of maximal mucositis and improved anorexia and swallowing ability. Indirubin may play a pharmaceutical role in improvement of radiation mucositis, anorexia, and difficulty in swallowing.

Small sample <30

Did not look at pain outcomes.

No information regarding adherence.

While this treatment may have some effect, the authors did not explore how the treatment was tolerated; patient adherence and side effects or medication interactions. Further research with this agent is warranted.

To evaluate the feasibility of therapeutic touch (TT) in preventing radiation-induced dermatitis in patients with breast cancer who are receiving radiation treatment

Women with stage I and II breast cancer who had received conservative surgery and were receiving adjuvant radiation therapy were recruited for the study. TT treatment was administered three times a week following radiation therapy. Feasibility was defined as a threshold of 15 of 17 patients completing all TT treatment. The preventive effectiveness evaluation was conducted by documenting the “time to develop” and “worst grade of radiodermatitis.” Patients were followed weekly while on treatment and for one week post-treatment.

• N = 49   
• AGE = 18–80 years
• FEMALES: 100%
• CURRENT TREATMENT: Radiation
• KEY DISEASE CHARACTERISTICS: Breast cancer
• OTHER KEY SAMPLE CHARACTERISTICS: Patient who had completed lumpectomy, sentinel lymph node biopsy, or axillary lymph node dissection

• SITE: Single site   
• SETTING TYPE: Outpatient    
• LOCATION: London Regional Cancer Program, London

PHASE OF CARE: Active antitumor treatment

Prospective case cohort study with two arms: The control arm received the TT treatment and the experimental arm received no treatment.

• Common Terminology Criteria for Adverse Events (CTCAE), version 3.0
• European Organization for Research and Treatment of Cancer (EORTC) cosmetic rating system
• EORTC Quality of Life Questionnaire Core-30 (EORTC QLQ-C30)
• Profile of Mood Status (POMS)
• Brief Fatigue Inventory (BFI)

Forty-nine patients participated in the study (17 in the TT and 32 in the control). A comparison of the two groups for the worst grade of radiodermatitis showed no difference (p = 0.661). The control group median time to develop the worst toxicity was 31 days (95% confidence interval [CI] [23, 35], standard error = 1.3767); in the TT group, it took 22 days to develop the worst toxicity (95% CI [18, 24], standard error = 1.769, p < 0.001). In the control cohort, the worst grade of radiation dermatitis was grade 3 noted in one patient; in the TT cohort, the worst grade was grade 2 noted in nine patients (53%). The most common toxicity grade in 15 patients was grade 2, and three patients did not develop toxicity. There was no difference between the cohort for overall EORTC cosmetic score and no significant difference before or after the study in quality of life, mood, or fatigue scores.

This study was the first evaluation of TT in patients with breast cancer using objective measures and, although it was feasible for the management of radiation induced dermatitis, it was not able to detect any significant benefit on the CTCAE toxicity grade. It also did not show any improvement in outcomes for fatigue, quality of life, or mood.

• Small sample (< 100)
• Risk of bias (no blinding)
• Risk of bias (no appropriate attentional control condition)
• Key sample group differences that could influence results
• Feasibility for radiation-induced dermatitis management but not for prevention

The primary purpose was to observe the effect of hypnosis on hot flashes and overall QOL in symptomatic patients. A secondary objective was to observe the effect of hypnosis on fatigue.

Each participant had four, one-hour per week sessions of hypnosis. The same physician, with the help of a nurse, conducted every session.

Ten healthy volunteers and four patients with breast cancer (total 14 patients) with hot flashes were enrolled.

All participants recorded frequency, duration, and severity of hot flashes in a hot flash diary.

The frequency (p < 0.0001), duration (p < 0.0001), and severity (p < 0.0001) of hot flashes were significantly reduced. The overall QOL was also improved (p < 0.05). The participants enjoyed better sleep and had less insomnia (p < 0.012). There was a significant improvement on current fatigue level (p = 0.017), but reduction in the total fatigue level was not statistically significant.

Study limitations included pilot study nature with a very small sample size; mixed healthy participants and people with breast cancer.

Patients met twice a week for 12 weeks for exercise and education. Outcomes were exercise tolerance, activity, sleep, and quality of life (QOL).

• The sample was comprised of 62 patients (31 men, 31 women).
• Mean age was 55 years.
• Patients had mixed ethnicity and varying cancer diagnoses and stages.
• Therapy included surgery, chemotherapy, radiotherapy, immunotherapy, and endocrine and hormonal therapy.

• Two major military medical centers
• Inpatient and outpatient
• Southwestern United States

Patients were either undergoing the active treatment or long-term follow-up phase of care.

This was a prospective, feasibility study with repeated measures.

• Wrist actigraphy to measure the duration of sleep, percentage of night spent asleep, average length of a sleep episode, and number of awakenings.
• Cancer Rehabilitation Evaluation System–Short Form (CARES-SF) sleep item

No improvement was found in sleep patterns per actigraphy; improved subjective rating was noted.

• This was a feasibility study; therefore, no control group was used.
• The study had a small sample size.
• Actigraphy data were missing.
• Cost is incurred for actigraphs.
• Staff must be trained in the exercise measurement.

To review research and guidelines regarding the use and potential benefits of exercise for patients with cancer undergoing treatment

Databases searched were Ovid, MEDLINE, and CINAHL (1980–2007).

• Studies involved male and female patients with cancer undergoing treatments. The majority of studies involved women with breast cancer. Other cancers included prostate, colon, lung, stomach, endometrial, head and neck, lymphoma, multiple myeloma, and melanoma. Patients undergoing bone marrow or stem cell transplant also were represented.
• Most studies involved patients with stage I or II disease, and some studies involved patients with metastatic disease. In patients with metastatic disease, as high as two-thirds were able to complete a 12-week program.
• Most exercise intervention studies with patients with cancer followed the American College of Sports Medicine recommendations.  

Stage of Disease:

• Evidence suggests that, although most studies recruited from patient populations with early stage I or II disease, even patients with metastatic disease have been able to exercise successfully.
• Stage of disease may influence exercise program completion rates.  In one study, however, almost two-thirds of the participants with stage III or IV disease were able to complete the 12-week intervention study. Patients appear to be able to safely and successfully exercise.

Types of exercise programs:

Most studies involved aerobic exercise, 11 studies included strength training, and 8 studies examined a combination of aerobic with strength training. None evaluated flexibility exclusively. 

Outcomes:

Compared to controls, the exercise groups improved cardiovascular and muscular fitness, experienced less fatigue, and slept longer. Exercise has been shown to improve almost all aspects of physiologic and psychologic functioning, including immune status. Of all the measures affected, cancer fatigue was the most improved. Although cancer fatigue has been thought to prevent patients with cancer from exercising, evidence has demonstrated that those who exercise experience less fatigue.

Frequency, intensity and adherence to exercise programs:

Participants exercised anywhere from 3–7 days a week for 2–52 weeks, for 10–45 minutes per session at 50%–85% of heart rate reserve. Adherence to the exercise prescription of frequency, intensity, time, and type ranged from 66%–78%. Typically, subjects in control groups started their own exercise programs (39%), such that diffusion of treatment effects can be an issue.

Interest:

In 2005, 63% of 187 participants agreed to join an exercise study, whereas in 2003, only 19% agreed to participate. Many hospital, clinics, and health clubs now offer programs specifically for cancer survivors. 

Concerns:

Concerns about exercise when undergoing cancer treatment have included bone metastasis, cardiac toxicities of therapies, and lymphedema. However, studies have shown that

• Patients with bone metastasis in nonweight-bearing bones safely can exercise.
• Exercise programs have been successfully tested to increase exercise tolerance in childhood cancer survivors who have received therapies with cardiac toxicities (e.g., anthracyclines, high-dose chemotherapy). In view of the paucity of information, one recommendation might be no exercise. However, based on the benefits of exercises in other patients with congestive heart failure symptoms, another recommendation would be to exercise as tolerated, reducing exercise intensity for symptoms, such as unusual fatigue, muscular weakness, shortness of breath, dizziness, faintness, or other unusual symptoms. 
• Exercise has been blamed for exacerbating or triggering lymphedema, theoretically because of increased blood flow and increased metabolic waste that could trigger an increase lymphatic flow and load on an already compromised system.  However, at least three clinical trials of women with breast cancer have shown no increased risk for or exacerbation of LE from either aerobic or resistance exercise.  The recommendation is to start lymphedema patients with exercise slowly, gradually increasing the time and intensity of the exercise sessions.

Because of lack of research, the best mode of exercise for patients with cancer has not been determined. At the same time, no mode in any of the studies reviewed here have been determined to be harmful. Of all the nonpharmacologic interventions for cancer-related fatigue recommended by the National Comprehensive Cancer Network (NCCN), exercise has the strongest evidence.  Any exercise prescription should include the components of frequency, intensity, time, type, and progression.  Issues regarding exercise prescription in patients with cancer relate more to the treatment side effects than to the cancer itself.  Since recovery from cancer treatment is unpredictable and side effects are individual in nature, collaboration between experts in cancer care and experts in exercise physiology is essential. In general, however, frequency and duration goals should be met before intensity goals and progression should be slower and more gradual for the deconditioned patient or those who are experiencing severe side effects of treatment.

Nurses can encourage exercise as part of a patient’s therapy and guide the patient to a safe program.

To assess the impact of prophylactic pyridoxine on hand-foot syndrome (HFS). The impact of urea ointment on HFS also was assessed.

Patients who were prescribed capecitabine at two hospitals between November 1, 2006, and October 30, 2007, received prophylactic pyridoxine 60 mg per day. The results were compared to those of a control group that did not receive prophylactic pyridoxine when the patients were prescribed capecitabine. Information on the prescription of urea ointment was available for the research group; 18 were prescribed urea ointment before HFS occurred.

• The study reported on a sample of 38 patients in the research group and 40 patients in the control group.
• Mean patient age was 55 years (range 31–88) for both groups.
• All patients in the research group were women. Gender in the control group is unknown.
• All patients had a cancer diagnosis.
• In the research group, capecitabine was given either as monotherapy or in combination with cyclophosphamide. This was the same in the control group, except some patients also received epirubicin.

• Multi-site
• Outpatient
   

Patients were undergoing the active treatment phase of care.

This was a retrospective study on patients treated with capecitabine with or without prophylactic pyridoxine.

• HFS was graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0.
• Standard response criteria
• Time to HFS was estimated using the Kaplan-Meier method and compared with the same historical data using the log-rank test.

• Twenty of the 38 patients receiving prophylactic pyridoxine (53%) developed HFS, compared with 83% of the 40 historical control patients who received no pyridoxine. 
• Pyridoxine did not appear to reduce the severity of HFS, but a nonsignificant trend toward delayed onset of HFS existed among patients receiving pyridoxine prophylaxis versus those without.
• A nonsignificant trend toward less-severe HFS also existed among patients who were prescribed urea ointment. 

Study findings did not support the effectiveness of pyridoxine in preventing HFS. Application of urea ointment may reduce the likelihood of developing HFS and prevent exacerbation to more severe HFS.  

•  The sample size was small (fewer than 100).
• The research group was all women. The authors proposed this may have affected the results, as women generally tend to care more about the condition of their skin on their hands and feet than men.
• The study had a retrospective design.
• Different chemotherapies were used in the study and control groups.
• Very limited sample demographic information was provided to determine key group differences that may have affected outcomes.
   

Because the data regarding prophylactic use of pyridoxine from this study contrasted with prospective data from a randomized phase 3 trial in patients with gastrointestinal disease, strongly recommending this approach is difficult. Evidence in this study is weak, and numerous limitations exist.

To test the feasibility of a new nonpharmacologic intervention to manage the symptom cluster of respiratory distress including breathlessness, cough, and fatigue in patients with lung cancer

Participants received psychoeducational counseling, which consisted of controlled breathing techniques, cough-easing techniques, acupressure, and supplementary information. Participants attended two one-hour face-to-face teaching sessions, the second session given one week after the first, and then received a telephone call two weeks after the second session. The interventions were delivered by a complementary therapy team. The training for the team consisted of one three-hour face-to-face session and a follow-up refresher at the half point of the trial. Participants were asked to complete a daily diary for the first four weeks and then weekly until week 12. Participants were also asked to assess and document the usefulness of each core component or intervention; and to practice breathing and calming techniques twice a day, use education for identifying warning signs of a cough, use a modified swallow technique and relaxed throat breathing, apply pressure to identified acupressure points for one minute at least twice a day, and review information in an information packet.

• N = 101   
• AGE = 67.7 years
• MALES: 47%, FEMALES: 53%
• CURRENT TREATMENT: Not applicable
• KEY DISEASE CHARACTERISTICS: Primary lung cancer
• OTHER KEY SAMPLE CHARACTERISTICS: Participants with an expected prognosis of at least three months, a World Health Organization (WHO) performance status of 0–2, and who were bothered with two of the cluster symptoms (breathlessness, cough, fatigue)

• SITE: Multi-site   
• SETTING TYPE: Outpatient    
• LOCATION: Two specialist cancer settings and two general hospitals in northern England

• PHASE OF CARE: Multiple phases of care
• APPLICATIONS: Palliative care 

• Randomized, controlled trial comparing the intervention group and the control group

Participants were randomized to either the control arm or intervention (RDSI) arm. Outcome assessments were collected at baseline, week 4, and week 12 at the end of the study. Breathlessness was measured using numerical rating scales and the dyspnea-12 scale, cough was assessed using the Manchester Cough in Lung Cancer scale (MCLC), and fatigue was assessed using Functional Assessment of Cancer Therapy–Fatigue (FACIT-F). In addition, the EQ-5D-3L was used to describe the value of quality of life (QOL), and the Hospital Anxiety and Depression Scale (HADS) was used to measure anxiety and depression.

Numerical rating scales were scored lowest for ease of use and relevance, and EQ-5D-3L was scored best for ease of use and relevance. Patients rated dyspnea-12 better for ease of completion and relevance, and EQ-5D-3L and HADS demonstrated a positive pattern in improvement for the intervention group. Participants reported a high adherence to interventions with breathing exercises and acupressure, and the lower use of cough-easing techniques was likely related to the lower number of participants bothered by cough in the intervention group. The majority of participants responded favorably to breathing exercises in responses, stating that it was useful at least a little bit, and cough and acupuncture responses also were favorable but had a higher number of responses saying that it was not useful at all. No significant difference existed in breathlessness between groups.

This study demonstrated the feasibility and acceptability of nonpharmacologic interventions to manage symptoms of breathlessness, cough, and fatigue in patients with lung cancer. The study gave insight to the best tools/instruments to measure outcomes for larger trials that will determine improved patient outcomes with interventions. This study also revealed patients' willingness to learn new strategies and complete study requirements for data collection. The results trended better outcomes in the treatment group, but the trial was not large enough to draw conclusions.

• Small sample (< 100)
• Risk of bias (no blinding)
• Findings not generalizable
• Subject withdrawals ≥ 10% 
• The sample size calculation indicated that a larger sample size is needed to determine whether or not the intervention resulted in improved patient outcomes and is cost-effective compared to the control group.

Nurses play an important role in identifying and managing patients with the respiratory distress symptom cluster. The study suggests the potential role for nurses to educate patients or to refer patients to complementary practioners who will instruct them on breathing techniques, cough-easing techniques, and acupressure.

Pilot the use of sweet bee venom pharmacopuncture to assess preliminary efficacy data

Six treatments were given by one certified oriental medicine doctor to patients over a three-week period. All patients were given skin tests prior to treatment. Adverse events were recorded after each session. The bee venom used incorporated melittin, an active extract from bee venom with allergens removed. The substance was injected into acupuncture points that were chosen in relation to the patients’ symptoms based on oriental medicine theory. Study measures were obtained at baseline; after two, four, and six treatments; and three weeks after treatments were completed.

• N = 8
• MEAN AGE = 49 years
• MALES = 25%, FEMALES = 75%
• KEY DISEASE CHARACTERISTICS: Various tumor types existed. Patients had received taxanes, cisplatin, carboplatin, or oxaliplatin.
• OTHER KEY SAMPLE CHARACTERISTICS: All had diagnosed peripheral neuropathy.

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

PHASE OF CARE: Late effects and survivorship

Prospective trial—case series

• World Health Organization (WHO) common toxicity criteria for peripheral neuropathy
• Peripheral neuropathy questionnaire
• Functional Assessment of Cancer Therapy—General (FACT-G)
• Common Terminology Criteria for Adverse Events
• Health-related quality-of-life questionnaire
• Visual analog scale (VAS)

Three patients who initially entered dropped out of the study—two due to symptoms that may have been associated with the injections, such as swelling and pain at the injection site and fever. Other therapies used by patients included red ginseng, herbal tonics, massage, foot/hand soaks, and pressure bands. All measures showed a decline in symptoms of peripheral neuropathy, and quality-of-life scores improved. VAS measures and WHO grade of peripheral neuropathy showed significant improvement (p ≤ .01).

Findings provide minimal evidence that sweet bee venom pharmacopuncture may have some benefit for treatment of chemotherapy-induced peripheral neuropathy. Half of the patients dropped out of the study, and 30% had probably adverse events from injections.

• Small sample of < 30
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Measurement/methods were not well described.
• Measurement validity/reliability were questionable.
• Subject withdrawals ≥ 10%
• All study measures used are not fully described.
• Multiple other herbal and other remedies also were used.
• Timing of the intervention related to antitumor therapy is not described.
• Follow-up period is short.

This pilot study provides some evidence to suggest that pharmacoacupuncture with sweet bee venom derivative is appropriate for further research to determine its potential efficacy and safety in larger well-designed trials.

To assess the noninferiority of 1 mg granisetron injection to 3 mg granisetron injection for the treatment of acute chemotherapy-induced nausea and vomiting (CINV)

Patients were randomly assigned to two treatment arms. All patients also received dexamethasone. Researchers asked the patients directly or via phone if they experienced any emetic events within 24–36 hours following the start of administration of highly emetogenic chemotherapy (HEC) or moderately emetogenic chemotherapy (MEC). Patients recorded their symptoms, along with use of rescue antiemetics, for six days on diary cards, which were collected at each visit.

• The sample consisted of 182 participants.
• Median age was 56 years, with a range of 23–80 years.
• The sample was 96% female and 4% male.
• Participants were patients with cancer who were scheduled to undergo chemotherapy and were stratified into the high- or moderate-emetic risk groups for CINV according to the American Society for Clinical Oncology (ASCO) guidelines for antiemetic treatment.
• The most commonly reported primary cancers were breast (n = 94), gynecologic (n = 64), primary unknown (n = 16), urothelial (n = 4), and sarcoma (n = 3). 

The setting was a single site in Tokyo, Japan.

Study participants were in active treatment.

This was a single-blind, randomized parallel group trial.

• Episodes of nausea were recorded by the patients on diary cards, along with the severity of the episodes according to the following 4-point scale: 0 = none (no nausea), 1 = mild (able to take meals as usual), 2 = moderate (reduced intake of food), and 3 = severe (unable to take either food or water).
• Patients also recorded any type or doses of antiemetic agents (i.e., rescue medications).
• Adverse events were evaluated based on the Common Terminology Criteria for Adverse Events (CTAE v3.0, Japanese version).

• Complete protection was achieved in 78% of the patients in the 1-mg group and 81% of the 3-mg group.
• The one-sided test did not reveal noninferiority of either dose of granisetron to the other at the 5% significance level.
• No significant differences were found between the groups for rate of complete response.

The rate of complete protection from nausea and vomiting was similar in both the 1-mg and 3-mg granisetron groups.

Nausea was measured as ability or inability to take meals as usual, rather than the symptom of nausea.

Granisetron dosed at 1 mg is appropriate for treatment of acute CINV in patients with cancer.

All patients received initial tooth brushing with a dental brush by a dentist and scaling to teeth with an ultrasonic scaler.

Special care group:
Dentist performed oral care with irrigation and suctioning for 15 minutes three days per week for two to four weeks between 7:00 pm and 8:00 pm after dinner. 20 ml of 0.5% povidone-iodine was ejected through the e-brush, then suctioned. This was done in the mouth, sides of the teeth, tongue, and mucosal surfaces. Patients rinsed with 0.5% povidone-iodine to clean the oral cavity. A combination of physical and chemical cleaning was used.
 

Patients with newly diagnosed esophageal squamous cell carcinoma (SCC) treated with chemoradiotherapy

The study was comprised of 40 patients (20 in the regular oral care group and 20 in the e-brush group).

The mean patient age was 66.2 years (SD = +/– 7.9 years) and 58.0 years (SD = +/– 6.3 years), respectively.
 

October 2003–January 2005

RCT

Oral mucositis was diagnosed by a dentist, assessed every Monday, Wednesday, and Friday.

Japan clinical oncology group criteria-based on NCI-CTC

Bacterial analysis
 

Incidence of oral mucositis was significantly lower in the special care group (4 of 20 [20%] versus 11 of 20 [55%] [p = 0.048]).

Induced stable microflora consisting of oral streptococci
 

Small study; labor intensive intervention; unclear about costs