The object of the systemic review was to assess the effectiveness of ketamine as an adjuvant therapy in treating cancer pain.

Medline (1996-2002); EMBASE (1980-2002); CancerLit (1966-2002); Cochrane Controlled Trials Registar and Database of Systematic Reviews (Cochrane Library, Issue 1, 2002); Specialized Registar of the Cochrane Pain, Palliative and Supportive Care Group (2001), PARDLARS (inhouse datadase of Pfizer UK, February 2002), hand searching reference lists

Two RCT met inclusion criteria. Two other RCT appeared to meet the criteria but were considered methodologically flawed. There were 32 case reports or open-label uncontrolled trials that could not be included.

Thirty patients, 17 men and 13 women, ages 21-69. Cancers included stomach, cervix, liver, lung, colon, pancreas, bladder, rectum, histiocytoma, and uterus. Study 1 with 20 had patients whose pain had been treated successfully with opioids. Study 2 had 10 whose pain had been unrelieved by their dose of morphine. Study 2 defined the pain as “neuropathic,” and the patients had a Karnofsky of 50 or more.

There was a reduction in pain scores for those receiving the ketamine. Four patients experienced hallucinations (most common adverse effect associated with ketamine). Two of these four patients also experienced a sensation of insobriety. All of these effects were relieved by diazepam.

Treatments evaluated:

• Ketamine 0.25 mg/kg adjuvant to morphine given IV
• Ketamine 0.5 mg/kg adjuvant to morphine given  IV
• Ketamine 1 mg/kg co-administered intrathecally with   morphine (reducing the morphine dose)

Outcomes Measured:

The primary outcome measure was patient-reported pain intensity and pain relief, using validated measures on movement and at rest ( e.g., visual analog scale and verbal rating scale).

Secondary outcomes included: total opioid consumption, rescue medication, adverse events, study withdrawals, and dropouts.

Because of the small number of RCTs , the small sample sizes, and the lack of other acceptable research, there is insufficient evidence for the use of ketamine as an adjuvant to opioids to make a recommendation for practice.

Suggested for research are crossover designs, larger patient groups, comparisons with other opioids, comparisons of routes of administration, and clearly defined outcomes. Research into ketamine’s role as an NMDA antagonist also would be welcomed.

DATABASES USED: MEDLINE (1996–2002); EMBASE (1980–2002); CANCERLIT (1966–2002); Cochrane Controlled Trials Register and Database of Systematic Reviews (Cochrane Library, Issue 1, 2002); Specialized Register of the Cochrane Pain, Palliative and Supportive Care Group (2001); PARDLARS (in-house database of Pfizer UK, February 2002); hand-searching reference lists

EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Two RCTs met inclusion criteria. Two other RCTs appeared to meet the criteria but were considered methodologically flawed. Thirty-two case reports or open-label uncontrolled trials could not be included.

FINAL NUMBER STUDIES INCLUDED = 2

TOTAL PATIENTS INCLUDED IN REVIEW: 30

KEY SAMPLE CHARACTERISTICS: Seventeen men and 13 women aged 21–69 years. Cancers included stomach, cervix, liver, lung, colon, pancreas, bladder, rectum, histiocytoma, and uterus. The first study included 20 patients whose pain had been treated successfully with opioids. The second study included 10 patients whose pain had been unrelieved by their dose of morphine. In the second study, pain was defined as “neuropathic,” and the patients had a Karnofsky score of 50 or more.

Pain scores were reduced in those patients receiving ketamine. Four patients experienced hallucinations (most common adverse effect associated with ketamine). Two of those four patients also experienced a sensation of insobriety. All of these effects were relieved by diazepam.

The following treatments were evaluated.

• Ketamine 0.25 mg/kg adjuvant to morphine given IV
• Ketamine 0.5 mg/kg adjuvant to morphine given  IV
• Ketamine 1 mg/kg co-administered intrathecally with morphine (reducing the morphine dose)

The primary outcome measure was patient-reported pain intensity and pain relief, using validated measures on movement and at rest (e.g., visual analog scale and verbal rating scale). Secondary outcomes included total opioid consumption, rescue medication, adverse events, study withdrawals, and dropouts.

The objective of the systematic review was to assess the effectiveness of ketamine as an adjuvant therapy in treating cancer pain. Because of the small number of RCTs, small sample sizes, and lack of other acceptable research, evidence is insufficient to make the use of ketamine as an adjuvant to opioids a recommendation for practice.

Suggested for research are crossover designs, larger patient groups, comparisons with other opioids, comparisons of routes of administration, and clearly defined outcomes. Research into ketamine’s role as an NMDA antagonist also would be welcomed.

To determine the efficacy and adverse effects of ketamine as an adjuvant to opioids in the treatment of cancer pain

Databases searched were CENTRAL, MEDLINE, EMBASE, PubMed, and the Pfizer Product Information Database.

Studies were included in the review if they

• Were randomized clinical trials (RCTs).
• Involved adult patients with cancer pain being treated with opioids.
• Studied patients receiving ketamine at any dose or route for cancer pain or a placebo or active control.

Studies were excluded if they had fewer than 10 participants.

A total of 120 references were retrieved. Studies were selected based on criteria, assessed independently, reviewed by two reviewers, and chosen for inclusion by three independent reviewers.

• The final number of studies included was two.
• The total number of patients included in the review across studies was 30.
• Of these patients, 20 were hospitalized with cancer pain unrelieved effectively with opioids who received two different doses of IV ketamine (0.25 mg or 0.5 mg) and 10 were patients with neuropathic pain unrelieved by opioids.

• Patients were at the end-of-life phase of care.
• This study has clinical applicability for palliative care.

• For IV ketamine, the 0.5 mg dose demonstrated a significant reduction in pain intensity and the relief was sustained throughout the three-hour measurement period.
• For intrathecal ketamine, pain was controlled on reduced doses of intrathecal opioids or on ketamine alone.

Current evidence is insufficient to assess the benefits and harms of ketamine as an adjuvant to opioids in the relief of cancer pain because of the small number of trials with low sample sizes.

• The sample size was small, with only 30 patients.
• Few RCTs exist on this topic.
• Doses and routes of administration of ketamine were different, measurement of pain was variable, the type of pain was variable (one study was of neuropathic pain but not the other), and the time for measurement was not consistent.

Although studies suggest that ketamine may be a helpful adjuvant therapy to improve pain and decrease opioid requirements in patients with cancer, more studies are needed with larger sample sizes and control groups. Evidence is lacking to recommend ketamine in practice.

• N = 67
• MEAN AGE = 59.6 years
• MALES: 41.5%, FEMALES: 58.5%
• KEY DISEASE CHARACTERISTICS: Patients had hematologic cancer (e.g., leukemia, lymphoma, myelodysplastic syndrome) or other oncologic illness and received care for at least five weeks
• OTHER KEY SAMPLE CHARACTERISTICS: 61.5% were spousal caregivers, and 16.9% were “offspring” caregivers; patients agreed to have their main caregiver involved in the study, and patients had approval for study participation from the doctor/psychological dyad

• SITE: Six acute care units, five different settings  
• SETTING TYPE: Multi-site  
• LOCATION: Clermont-Ferrand, France

• PHASE OF CARE: Active treatment

• Randomized, controlled trial
  • Patient-caregiver dyads were assigned to the experimental or control group using randomization software

• SF-36 health survey (patients and caregivers self-administered)—used to assess eight health dimensions
• Zarit Burden Scale (caregivers self-administered)—used to assess three dimensions of burden
• Questionnaire for satisfaction of hospitalized patients (patient self-administered)—used to assess eight factors related to scope of hospital experience

No difference was seen in quality of life scores between the control (N = 34) and experimental (N = 33) patient-caregiver dyad groups at the first testing. Evaluation (pre- and post-test scores) supported improved quality-of-life scores in the experimental group patient-caregiver dyads as compared to those in the control group. Patients in the experimental group showed significant improvement on two of six dimensions (physical role [p = 0.039] and general health [p = 0.037] on the quality-of-life measure. Experimental group caregivers showed significant improvement on six of eight dimensions (physical role, emotional role, vitality, mental health, social functioning, and general health, all p < 0.05) on the quality-of-life measure. The average score of burden of care in the experimental group (M = 16, SD = 9.9) was significantly lower than that of control group (M = 31.4, SD = 14.9) at last evaluation (p < 0.001). Evolution scores for burden also showed significantly (p = 0.004) less perceived burden among experimental group caregivers as compared to control group caregivers. Patient satisfaction scores of patients in the experimental and control groups showed no difference, except patients in the experimental group showed a significant improvement in relationship with nurses (p = 0.037) because of program involvement.

Nurse-provided educational interventions tailored to caregiver needs and patient expectations may minimize caregiver burden and improve patient and caregiver quality of life. These interventions, if provided during patients’ acute setting care, may pave the way for more effective patient home care by informed and involved caregivers.

• Small sample (less than 100)
• Risk of bias (no blinding)
• Risk of bias (no appropriate attentional control condition)
• Findings not generalizable
• Other limitations/explanation: Authors acknowledge strict inclusion and exclusion criteria that influenced the loss of 110 of 265 participants initially assessed for the study. Author conclusions note a need for a less rigorous program to meet patient and caregiver needs for those who do not meet more stringent criteria found in an RCT used in this study. Whether nurses who were members of the research team delivered the intervention and could connect knowledge of individual patients/caregivers to study results is unclear. Which of the four teaching categories influenced caregiver quality of life and burden the most also is unclear.

Nurses who deliver evidence-based, tailored educational interventions to family cancer caregivers may increase patient-caregiver quality of life and minimize caregiver burden during cancer care. Stronger nurse-patient relationships, based on interaction during caregiver task teaching, may facilitate patient care satisfaction and coping during the cancer experience.

To investigate the effects of acupressure on anxiety in patients with cancer

Patients were randomly assigned to acupressure, sham acupressure, or control groups. Control group patients received usual care. The acupressure group had pressure applied at nine points for two minutes each by a research assistant. Sham acupressure was also given at nine different points on the body. Patients received 10 sessions of sham or actual acupressure. Study measures were obtained at baseline, after session 5, and after session 10.

• N = 85
• MEAN AGE = 48 years
• MALES: 54.1%, FEMALES: 45.9%
• KEY DISEASE CHARACTERISTICS: 51% had stage 4 disease
• OTHER KEY SAMPLE CHARACTERISTICS: The majority had prior surgery and chemotherapy

• SITE: Single site  
• SETTING TYPE: Inpatient  
• LOCATION: Iran

Double-blinded, sham-controlled, randomized trial

• Spielberger State/Trait Anxiety Inventory (STAI)

Mean anxiety scores in the acupressure group declined over the three study measurement periods (p = 0.001). Anxiety scores in the sham group also declined somewhat. Anxiety levels in the control group increased over time. An analysis of variance showed that acupressure was associated with a significant reduction in state anxiety scores and a significant difference in comparison to the control group patients (p < 0.0001). There was no significant difference between acupressure and sham acupressure changes.

Both sham and actual acupressure were associated with reductions in anxiety scores.

• Small sample (< 100)
• Other limitations/explanation: The timing of postintervention anxiety measurements were not clear, but it appears this was done immediately after the sham or acupressure interventions. The actual clinical relevance of an immediate short-term change is not clear.

The findings of this study suggest that acupressure may be of some benefit in the short-term management of anxiety among patients with cancer. The findings regarding the effects of sham acupressure suggest there may be a placebo effect involved. Additional well-designed research would be helpful to demonstrate the role of acupressure in the management of anxiety.

To investigate the effects of adenosine 5'-triphosphate (ATP) infusions on quality-of-life (QOL) parameters in patients with preterminal cancers of mixed tumor types.

Patients were randomized to the usual care control group with standard nutritional advice or to the intervention of usual care, nutritional advice, and ATP infusion. An eight- to 10-hour ATP infusion was given weekly, with a maximum dose of 50 µ/kg/minute.

• In total, 83 patients (23 women, 60 men) (ATP, n = 44; control, n = 39) were included.
• Age ranged from 54 to 78 years.
• Patients were undergoing curative treatment for lung, colon, gastrointestinal, prostate, and other types of cancer.
• Patients reported fatigue and had weight loss greater than 5% or anorexia.

• The study was conducted at multiple sites in The Netherlands.
• The initial dose was given at the daycare centers of participating hospitals and then patients were infused at home.

The study was a randomized, controlled trial.

• Quality of Life Questionnaire
• Groningen Activity Restriction Scale (GARS)
• Dutch Short Fatigue Questionnaire
• Jamar Hydraulic Hand Dynamometer
• MicroFET 2 Dynamometer

• Between the ATP and control groups, no statistically significant differences were observed in QOL, functional status, or fatigue.
• Elbow flexor muscle strength had an almost significant increase in the control group (1.98).

Better survival was observed during the eight-week intervention in the ATP group. The rationale was that palliative cancer drugs cause serious side effects. The authors concluded that that may be an advantage of the ATP treatment.

• The study had a small sample size, with less than 100 patients.
• The increased drop-out may have limited the power of the study.
• Large heterogeneity existed between patients.
• The eight-week intervention was shorter than other studies of 12 weeks.

The study provided little useful information for nurses.

To determine whether an exercise-based intervention was safe and effective for breast cancer survivors

• N = 67  
• AVERAGE AGE = 55.1 years
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: Breast cancer 

• SITE: Single-site    
• SETTING TYPE: Home    
• LOCATION: United States

• PHASE OF CARE: Late effects and survivorship

Quasiexperimental

• Height and weight
• Physical activity outside of weight lifting
• Perometry
• National Cancer Institute's Common Terminology Criteria for Adverse Events–Lymphedema (NCI-CTCAE-L) version 3
• Muscular strength 
• Semistructured interviews 

The number of lymphedema symptoms reduced from baseline to the 12-month follow-up visit (2.6 [SD = 2.6] to 1.7 [SD = 2.1], p = .002), but there was no statistically significant reduction in the severity of lymphedema symptoms from baseline to the 12-month follow up visit (p = .58). In addition, there was no difference in arm volume, measured as a percent of interlimb difference, at the 12-month follow-up visit (p = .98). Within this sample, four patients (8%) had new-onset lymphedema at the 12-month measurement and five (19%) had a flare-up of existing lymphedema.

The PAL intervention reduced the number of lymphedema symptoms but not the severity of symptoms experienced by participants. In addition, the intervention did not reduce the limb volume of participants. Participants were able, however, to complete the intervention, which took place mostly in the home setting, making it a feasible intervention for women with breast cancer.

• Small sample (< 100)
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Unintended interventions or applicable interventions not described that would influence results
• Other limitations/explanation: It is unclear what other exercises participants were doing at home.

When available, home-based exercise interventions like the ones described here may be beneficial for patients who are motivated to participate in and complete exercises at home. Nurses should assess patients for readiness to participate in a home exercise program and help patients find resources for planning an appropriate home-based program.

STUDY PURPOSE: To assess the evidence regarding the use of corticosteroids for fatigue among patients with advanced cancer

• FINAL NUMBER STUDIES INCLUDED = 4
• TOTAL PATIENTS INCLUDED IN REVIEW = Not provided
• SAMPLE RANGE ACROSS STUDIES: Not provided
• KEY SAMPLE CHARACTERISTICS: All studies were of patients with advanced disease with minimal life expectancy.

SAMPLE RANGE ACROSS STUDIES, 

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

All studies reported improvement in patient-reported fatigue. Gaps were noted in information regarding side effects and the specifics of the dosage, etc., of the intervention.

Corticosteroids may improve fatigue in patients with advanced cancer, but potential adverse side effects have not been examined well.

• Limited number of studies
• No details of included studies, such as sample sizes, etc., were provided.

Corticosteroids may improve fatigue in patients with cancer, but insufficient information about adverse effects exists. Steriods should not be used for a long duration—an intervention that may be useful for patients who desire short-term improvement in feelings of fatigue to participate in family events, etc.

 To determine the effect of acupuncture on hot flash (HF) frequency and intensity, quality of life, and sleep quality in patients undergoing hormonal therapy for prostate cancer.

Men with HF scores greater than four who received androgen-depriving therapy underwent acupuncture with electrostimulation biweekly for four weeks then weekly for six weeks using a predefined treatment plan. Patients completed a Hot Flash Diary daily for seven days prior to treatment then daily throughout the study.

• The sample was comprised of 22 males with prostate cancer.  
• Median age was 71 years.
• Patients were undergoing androgen deprivation therapy.

The study enrolled men with prostate cancer who were treated with bilateral orchiectomy, gonadotropin-releasing hormone agonist, or antagonists with or without antiandrogen therapy. The sample group reported at least four HFs per day. They could not be receiving concurrent chemotherapy, estrogens, progesteronal agents, or gabepentin. They had to be off of selective serotonin reuptake inhibitor (SSRI) class antidepressants for at least two weeks; however, the SSRI prohibition was removed after 16 patients were enrolled to speed accrual. Patients with pacemakers or other electrical devices were excluded.

• Single site   
• Outpatient   
• Sweden

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

The study used an open-label, single arm, phase II design.

• Hot Flash Related Daily Interference Scale (HFDIS)
• Pittsburgh Sleep Quality Index (PSQI)
• Short Form 36-item Health Survey (SF-36)
• Blood samples plasma calcitonin gene-related peptide (CGRP)
• Urine samples 5-HIAA
• Hot Flash Diary

Acupuncture treatment was administered twice weekly, with an attempt to use the same practitioner throughout the treatment period. Specific acupuncture sites were used in all patients. The HF score was calculated from the Hot Flash Diary, and each HF was calculated to determine severity. The severity-adjusted HF scores were summed for seven days. Biomarkers were assessed at baseline; 2, 4, 6, and 10 weeks of treatment; and again after 6 weeks. The mean HF score was reduced after four weeks of therapy, then reduced to 52% of baseline at eight weeks. The HFDISs were available for 21 of the improved patients. The PSQI was available for 19 patients, but there was no statistical significance noted from baseline to after 10 weeks of treatment. No improvement in overall vitality was measured by the SF-36. No significant adverse effects were noted. Regarding the biomarkers, no change in the serum serotonin levels was noted for any patient. Urinary 5-HIAA had a nonsignificant trend toward reduced 5-HIAA concentrations, with the nonresponders (two patients) having an increase over time. The nonresponders' 5-HIAA concentrations were 129% of baseline, whereas the responders at week 10 showed 73.3% of baseline concentrations. The CGRP levels baseline sample results were so diverse that subsequent samples obtained during and posttreatment detected no meaningful differences. The variability in the CGRP samples reduced the statistical power of the study to detect differences.

The study suggested that acupuncture may be an active nonpharmacologic option for patients with prostate cancer experiencing HFs while undergoing hormonal treatment.

• The study had a small sample size, with less than 30 patients.
• Hot flash Diaries were incomplete beyond week 8, so the severity of hot flashes was not calculable past the time point proposed.
• The variability in the CGRP samples reduced the statistical power of the study to detect differences.

Further research is needed in the use of acupuncture in reducing HF scores and improving sleep quality in prostate cancer survivors. Further research may also be needed  to determine if differences exist between genders for HF distress/occurrence and sleep quality, which may provide some direction for extrapolating research results with either gender group.

STUDY PURPOSE: To review the evidence for axillary reverse mapping (ARM) and discuss the feasibility, safety, and relevance of this procedure

TYPE OF STUDY: General review/"semi" systematic

• FINAL NUMBER STUDIES INCLUDED = 31 
• TOTAL PATIENTS INCLUDED IN REVIEW = 2,747
• SAMPLE RANGE ACROSS STUDIES: 23–327
• KEY SAMPLE CHARACTERISTICS: All had breast cancer surgery involving ARM

PHASE OF CARE: Active antitumor treatment

Evidence shows a wide range of visualization rates from 20%–90% and notes that rates are lower with sentinel lymph node biopsy (SNLB) than with axillary lymph node dissection (ALND). The definition of successful ARM, the volume of blue dye used, and the experience of the surgeon varied, all of which may affect these rates. Blue dye, flourescent dye, and radioisotopes have been used for visualization. No adverse events from the procedures have been noted. At present, no axillary recurrence has been reported in patients in whom lymph nodes were preserved. ARM may contribute to a reduction in upper extremity lymphedema, although current evidence is not strong enough to draw firm conclusions.

The preservation of lymph nodes with ARM appears to be safe and may contribute to a reduction in the incidence of upper extremity lymphedema.

• No quality evaluation
• Most studies had a relatively short follow-up time frame.

The preservation of axillary lymph nodes in women undergoing surgery for breast cancer with ARM appears to be safe. The evidence suggests that ARM with lymph node preservation may reduce the prevalence of arm lymphedema; however, multiple limitations in the available evidence exist. Ongoing research of the long-term effects on patient outcomes is needed and underway.