To observe functional and symptomatic changes related to quality of life in patients with advanced gastric cancer with administration of Jinlongshe granule (JLSG, a Chinese herbal medicine)

Patients were randomized into a JLSG group or a placebo group. All patients received Chinese medicinal herbs prescribed individually. The intervention arm additionally received JLSG, and the other arm received a placebo three times daily. Patients were followed biweekly in clinic visits. Study measures were obtained at enrollment and at 3, 6, 9, 12, and 15 months after treatment.

• N = 39  
• AGE: Mean and range not determinable
• MALES: 66.7%, FEMALES: 33.3%
• KEY DISEASE CHARACTERISTICS: All patients had advanced gastric cancer and most had liver metastasis.
• OTHER KEY SAMPLE CHARACTERISTICS: Inclusion criteria included expected three-month survival.

• SITE: Single-site    
• SETTING TYPE: Outpatient    
• LOCATION: China

• PHASE OF CARE: End-of-life care
• APPLICATIONS: Palliative care 

Double-blind, placebo-controlled, randomized clinical trial

• European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ–C30)

There were statistically significant group-by-time effects for multiple symptoms including cognitive function, fatigue, pain, dyspnea, insomnia, appetite loss, constipation, and and general quality of life (p < .05). For some symptoms, differences were due to increased symptoms in the placebo group. No information regarding any adverse effects is reported. The direction of change in symptom scores is not always clear in this manuscript.

This study has several limitations that make it difficult to assess the potential efficacy of JLSG for symptom management.

• Small sample (< 100)
• Unintended interventions or applicable interventions not described that would influence results
• Measurement validity/reliability questionable
• Findings not generalizable
• Subject withdrawals ≥ 10%  
• Other limitations/explanation: All patients received a variety of Chinese herbal medications that were not described and were not standardized; therefore, it is not possible to determine the actual effect of the JLSG. No other interventions aimed at symptoms are described. Repeated measures of the same instrument may produce testing effect.

This study provides minimal evidence in support of a specific Chinese herbal medicine in patients with advanced gastric cancer. Further well-designed studies are needed for clinically meaningful evaluation of efficacy.

This intervention was a 30-minute, full-body massage delivered by the first author after completing pre-test. After the intervention, the participant was instructed to lie quietly for 30 minutes before completing the post-test.

• N = 30
• KEY SAMPLE CHARACTERISTICS: Taiwanese hospitalized patients with metastatic bone pain

• Quasi-experimental design

• Pre-test/post-test measures
• Repeated to examine the time effects of massage

Massage was shown to have effective, immediate, short-term (20–30 minutes; a 61% reduction in anxiety), intermediate (1–2.5 hours), and long-term benefits (16–18 hours) on present pain intensity and anxiety. The most significant reduction in anxiety occurred 15–20 minutes after the intervention. The results from ANOVA revealed a time effect of massage on anxiety visual analog score across time at a statistically significant level (F [10, 20] = 10.3, p < 0.001).

• Convenience sampling
• Small sample size
• Quasi-experimental design
• Lack of a control condition and possible response bias
• Well designed but not randomized

To evaluate the effects of pericardium 6 (P6) acupressure and nurse-provided counseling on chemotherapy-induced nausea and vomiting (CINV) in patients with breast cancer

Participants were randomized to one of four treatment groups. The control group received sham acupressure on SI3 point—the ulnar side of the metacarpophalangeal joint of the little finger of both hands. The three experimental groups consisted of counseling only, P6 acupressure-only, and P6 acupressure and counseling.

Counseling consisted of a one-hour cognitive behavioral session which included an introduction, cognitive preparation, symptom acceptance, the use of available resources, and question and answer session. Participants were instructed to perform the cognitive-behavioral session daily for 5 days (C2, D 1-5). 

The P6 acupressure groups wore Sea-Band® bands on both wrists for 5 days.

All participants completed baseline data then received a booklet of instruments and a daily log. They were asked to check their gastrointestinal (GI) distress level nine different times the evening of the first day of cycle 2 of chemotherapy and then once in the morning and once in the evening of days 2–5. Patients were asked to keep a daily log of the antiemetic medications taken and the overall status of their GI symptoms. The research assistants called each participant once and sent two text messages during the 5-day period to increase adherence.

• The study consisted of 105 patients.
• The mean age of patients was 45 years (SD = 8.661). To be included, patients must have been older than 20 years.
• All of the patients were female and had been diagnosed with stage I-III breast cancer.                                                       
• Participants had previously received definitive breast surgery and were currently undergoing the second cycle of adjuvant chemotherapy with either the FAC (5-fluorouracil, Adriamycin, and cyclophosphamide) or ACT (Adriamycin, cyclophosphamide, and paclitaxel) regimen. All participants had experienced more than mild levels of nausea and vomiting with the first cycle of chemotherapy.  
• Patients who agreed to participate had their level of acute and delayed nausea measured on the 5th day of the first cycle, and only those with an average nausea level of more than 4 on a scale of 1–10 were included in the study.
• More than half of the participants had at least some college education, claimed a religion, were married at the time of the data collection, had stage II breast cancer, and had received the FAC regimen.
• Antiemetics used were granisetron (39%), aprepitant plus dexamethasone (30%), aprepitant only (20%), and ondansetron (9%).
   

This study was conducted at a single outpatient setting in Seoul, South Korea.

All patients were in active treatment.

This was a randomized, controlled trial.

• The Index of Nausea, Vomiting and Retching (INVR, Rhodes & McDaniel) self-report instrument was translated into Korean to measure frequency, distress, and duration of nausea, vomiting, and retching.
• Antiemetic medications taken and the severity of GI distress were reported daily in logs.

• CINV levels were significantly different among the groups from day 2 to day 5.
• These differences were attributed mainly to the difference between the control group and the group with P6 acupressure plus nurse-provided counseling (p = 0.01).
• The effects of acupressure were proven from day 2 to day 5 (p = 0.005, 0.002, 0.001, 0.001 respectively), and the effects of the nurse-provided counseling were proven on day 4 (p = 0.025) and close to significance on day 5.

Synergic effects of P6 acupressure with nurse-provided counseling appeared to be effective in reducing CINV in patients with breast cancer.

• Generalizability is limited because the study involved only women in one cancer center.
• The relatively small sample size of each treatment group may have limited that ability to measure the isolated effect of either P6 acupressure or counseling.  
• Substantially different antiemetics were used in the different study groups. 
• Overall, 17% of patients dropped out before completing the study.

The addition of P6 acupressure and nurse-provided counseling focused on cognitive awareness, affective readiness, symptom acceptance, and the use of available resources both appear to be effective as adjuncts to antiemetic medicine for the control of CINV in patients with breast cancer.

To assess the efficacy of caffeine infusion as an adjuvant analgesic for patients with advanced cancer on opioids for chronic pain

Patients were randomly assigned to either a caffeine group or a placebo group. The caffeine group was given 200 mg of caffeine intravenously over one hour daily for two days. The placebo group was given normal saline. Pain was assessed before the intervention, one hour after the infusion on day 1, before the intervention on day 2, and one hour after the intervention on day 2.  Adverse events were assessed during interventions and two hours later.

• The study reported on a sample of 38 patients.
• Mean patient age was 65.67 years (SD = 10.88 years).
• The sample was 51.2% female and 48.8% male.
• All patients were receiving palliative care and were not undergoing current treatment. Multiple tumor sites were represented.
• All patients had pain levels of 6 or less on a numeric rating scale.

• Single site 
• Inpatient setting
• South Korea

• Patients were undergoing end-of-life care.
• The study has clinical applicability for palliative care.

A randomized, double-blind, placebo-controlled design was used.

A numeric rating scale (0–10) was used to measure pain and adverse effects.

Pain was significantly lower after the second trial, day 2, in those receiving caffeine (p = 0.038); however, the difference between groups in pain severity decline was extremely small. In those receiving caffeine, the decline in pain scores pre-post day 2 infusion was 0.83 (mean) and in those on placebo, the change was 0.81 (mean).

This study does not provide strong support for efficacy of caffeine infusion as an adjuvant analgesic compared to placebo for patients with pain associated with advanced cancer.

• The study had a small sample, with less than 100 participants.
• There was no analysis of differences in any rescue medication use.

This study does not provide strong evidence for or against the use of caffeine infusions as adjuvant analgesia in patients with pain associated with advanced cancer.

To assess the efficacy of folinic acid administration post-methotrexate treatment for graft-versus-host disease (GVHD) prophyllaxis on the incidence of oral mucositis and acute GVHD

A retrospective analysis of 118 consecutive patients who underwent allogeneic hematopoietic stem cell transplant (HSCT) and received methotrexate (MTX) for GVHD prophylaxis between March 2006 and December 2009. Systemic folinic acid (given at the same dose as used for methotrexate administration on additional days of treatment) and folinic acid mouthwash (13% folinic acid 4 times per day on days 1–7) were given according to physician discretion.

• The sample consisted of 118 patients with an age range of 17–68 years.
• The sample was 52% male and 48% female.
• Patient diagnoses were acute myelogenous leukemia (AML), acute lymphocytic leukemia (ALL), myelodysplastic syndrome (MDS), chronic myelogenous leukemia (CML), Hodgkin lymphoma (HL), non-Hodgkin lymphoma (NHL), adult t-cell leukemia/lymphoma (ATLL), multiple myeloma (MM), AA amyloidosis, and mycosis fungoides (MF) undergoing HSCT.

The study was conducted at a single site in the Stem Cell Transplant Center of Hokkaido University Hospital in Japan.

Patients were underoing the active treatment phase of care.

The study was a retrospective analysis of 118 consecutive patients between March 2006 and December 2009.

The National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was used.

The incidence of oral mucositis (p = 0.00063) and severe oral mucositis (grade 3 or 4) was significantly lower in patients who received systemic folinic acid than in those that did not (p = 0.0005). Oral mucositis occurred in 77.1% of patients, and grade 3-4 mucositits occurred in 31.4%. No significant difference was found in the incidence of acute GVHD on day 100 post-transplant between the systemic folinic acid and non-folinic groups. Oral mucositis did not correlate with the development of severe GVHD, and no significant differences were found in the incidence of relapse between the two groups. Multivariate analysis showed that the odds of developing severe oral mucositis was significantly associated with a longer duration of severe neutropenia (> 21 days) (OR 4.78, p = 0.0019) and systemic folinic acid administration (OR 0.13, p = 0.014).

Folinic acid administration reduced the incidence of severe oral mucositis. The strongest association with the development of severe oral mucositis was longer duration of severe neutropenia.

• No appropriate control group was included.
• Use of systemic folinic acid was random, based on physician preference.
• Use of folinic acid mouthwash was also random (approximately 50%), and it was not known if it was used with the systemic or not.

Further randomized controlled studies are needed to assess the efficacy of systemic folinic acid plus or minus folinic acid mouthwash. Further studies are also needed to clarify the cost effectiveness of this treatment regimen. Findings suggest that prolonged severe neutropenia is an important factor in the development of severe oral mucositis.

Immediate-release methylphenidate was given at a dose ranging from 5 to 30 mg per day; 11 of 16 patients were given 10 mg per day. The study was based on the hypothesis that methylphenidate may improve fatigue by counteracting the adverse effects of opiates or relieving depression.

Posttreatment assessment was conducted as soon as two days after the initiation of therapy (median of seven days after initiation of methylphenidate).

• In total, 16 patients (6 females, 10 males) were included.
• Five patients had lung cancer and 11 had a mixed group of solid tumor diagnoses.
• Half of the sample was experiencing pain, and nine were taking corticosteroids.
• Four patients had been diagnosed with major depression before the initiation of the study.

• Inpatient and outpatient
• One of two large comprehensive cancer centers

Patients were undergoing the end of life phase of care.

This was a prospective, open-label, pilot study.

A visual analog scale (VAS) was used to assess fatigue before premethylphenidate and after a median of seven days.

A statistically significant difference was found between the mean fatigue score before treatment with methylphenidate and the fatigue score after treatment. Following treatment with methylphenidate, patients reported lower fatigue scores, and six patients were classified by the investigators as having responded (defined by the investigators as a 30% improvement in fatigue severity score from pre- to posttreatment) to treatment with methylphenidate. Concomitant depression and the use of opioids did not predict methylphenidate efficacy. Two patients discontinued because of insomnia, and one reported mild palpitations but opted to continue methylphenidate. Adverse reactions reported generally were limited.

• This was a small, convenience sample, with an open-label design and no comparison group that used only one fatigue measure.
• Patients received different dosages of methylphenidate.

To investigate the safety and efficacy of a novel arm sleeve composed of a conventional arm sleeve extending to a wider area of the body

Subjects who already used their own arm sleeves used a new conventional arm sleeve during the daytime for two weeks, followed by a novel sleeve during the daytime for two weeks. The characteristics of the arm part of the novel sleeve are the same as those of the arm part of the conventional sleeve. A large elastic body piece to cover the shoulder and the body trunk was attached to the novel sleeve. During the study, the subjects were allowed to use their own mittens or gloves.

• N = 5
• MEDIAN AGE = 70 years (range = 48–78 years)
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: Postmastectomy upper extremity lymphedema; stage 2 lymphedema; and in the maintenance phase of complex physical therapy (i.e., all subjects used their own sleeves prior to enrolling in the study)

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

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

Pre- and post-test design with repeated measures

• Arm circumference
• Questionnaire for arm-related symptoms
• Interface pressure measured using an air pack-type analyzer
• Subcutaneous fluid distribution measured by magnetic resonance imaging

When a new conventional arm sleeve was provided to participants, total arm volume (p < 0.05) and percentage of arm volume (p < 0.05) was reduced. When participants were given the novel sleeve, arm volume and percentage volume were reduced, but these changes were not statistically significant.

The novel arm sleeve was associated with some additional reduction in arm volume, but these changes were not significant. The conventional arm sleeve, however, did produce a significant reduction in arm volume when a new sleeve was provided to participants.

• Small sample (< 30)
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Risk of bias (no appropriate attentional control condition) 
• Findings not generalizable

The sample for this study was extremely small, making the results difficult to generalize. Although the study showed that the novel arm sleeve provided some benefits for the management of arm lymphedema, well-designed studies with larger sample sizes are needed to replicate and examine the effectiveness of this intervention.

DATABASES USED: MEDLINE, EMBASE

• FINAL NUMBER STUDIES INCLUDED = 4
• TOTAL PATIENTS INCLUDED IN REVIEW = 917
• KEY SAMPLE CHARACTERISTICS: Chitapanarux et al. study—63 female patients receiving RT and cisplatin chemotherapy for cervical cancer; Delia et al. study—490 patients receiving RT for colon, rectal, or cervical cancer; Germain et al. study—246 patients receiving RT for rectal, cervical, endometrial or prostate cancer; Giralt et al. study—118 patients receiving RT and cisplatin chemotherapy for cervical or endometrial cancer

PHASE OF CARE: Active antitumor treatment

The Chitapanarux and Delia studies were most robust and the Giralt study was least robust. The Germain study could not be determined. There were no adverse events reported in the studies. The Chitapanarux and Delia studies determined that probiotics were beneficial and produced statistically significant results in the study population. The Germain study reported benefits that were statistically significant at standard dose and at high dose, which was not statistically significant. Studies revealed high clinical significance.

Evidence supporting contention that probiotics are beneficial is low quality.

• Scope
• Objectivity
• No second reviewer

More research is needed on the use of probiotics with rigorous randomized placebo controlled studies.

Patients were given 20 mL aloe vera solution or placebo to swish and swallow four times per day beginning on the first day of radiation therapy (RT) and continuing throughout the treatment course. The  solution consisted of 94.5% aloe juice, 5.0% pear juice concentrate, 0.4% lemon-lime flavor, and 0.1% citric acid. The placebo solution was taste-matched with identical astringency, consistency, and ingredients, except that the aloe vera juice was replaced with water.

The study reported on 58 patients with stage II-IV M0 head and neck cancer who were scheduled to receive radiation of at least 50 Gy to at least one site; 28 patients were given aloe vera, and 30 were given placebo.

The study was conducted from February 1999 through March 2002.

This was a double-blind, placebo-controlled, randomized trial.

• Researchers recorded incidence and duration of mucositis.
• Secondary endpoints were quality of life (QOL), weight loss, use of pain medications, need for IV hydration, oral infections, and duration of treatment interruptions.
• The toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and patient-completed QOL questionnaires were completed every two weeks.

• The aloe vera arm recorded a lower maximal mucositis severity grade; however, the difference was not statistically significant.
• Incidence of grade 2 or worse mucositis was not statistically significant between the groups. The treatment group had lower QOL scores, but the differences were not significant.
• Both arms had similar outcomes for other dimensions.
• The authors concluded that the addition of aloe vera did not improve tolerance to head-and-neck RT; decrease objective measurements of mucositis; or improve QOL ratings of health, soreness, or well-being.

Findings were not significant.

This study did not accrue adequate patients according to statistical analysis.

PHASE OF CARE: Active antitumor treatment
 
APPLICATIONS: Palliative care

CHM used alone or in combination with chemotherapy or supportive care showed significant relief in CRF compared to placebo, chemotherapy, and supportive care based on single trials. CHM plus chemotherapy or supportive care was superior to chemotherapy or supportive care in improving quality of life. Data from one trial demonstrated that CHM exerted a greater beneficial effect on relieving anxiety but no difference in alleviating depression. Seven trials reported adverse events, and no severe adverse effects were found in CHM groups.

The work suggests that CHM may be effective and safe in the treatment of CRF. However, the current evidence is insufficient to draw a confirmatory conclusion due to the poor methodological quality of included trials.

Quality of methods:

• Lack of information about randomization
• No blinding of participants or providers
• Few adequate allocation concealment
• Short-term interventions (approximately four weeks)

It is necessary to conduct rigorously designed trials on potential CHM.