Evaluate the impact on chemotherapy-induced peripheral neuropathy (CIPN) associated with the MC5-A Calmare^® therapy device.

Participants were recruited from the clinical oncology practice by physician referral and advertisements in the waiting rooms. The MC5-A device was applied daily to areas of CIPN determined and assigned to dermatomes. The treatment time was 60 minutes for 10 days. The MC5-A device is intended to induce modulation of pain responses with low frequency simulation to nerves with surface electrodes, raising the “gate” threshold for pain at the spinal cord. Patients were evaluated at baseline and at the end of weeks 1 and 2 of treatment, and then at the end of weeks 4, 8, and 12. Subjects rated their pain immediately before and after treatment.

• N = 16 (were evaluable)
• MEAN AGE = 58.6 years (SD = 10.6 years)
• MALES = 22%, FEMALES = 77%
• KEY DISEASE CHARACTERISTICS: The most frequent diagnoses were breast and colon cancer. The most common chemotherapy drugs that were used were taxanes, platinum, and bortezomib. All subjects had unstable CIPN for at least three months.
• OTHER KEY SAMPLE CHARACTERISTICS: Ten subjects were Caucasian, 6 were African American, 1 was Native American, and 1 reported \"other.\" Ten patients were previously treated for pain with opioids; 4 were treated with gabapentin monotherapy; and others were treated with various drug combinations.

• SITE: Single site
• SETTING TYPE: Outpatient
• LOCATION: Massey Cancer Center, Virginia Commonwealth University, in Richmond, VA

• PHASE OF CARE: Active treatment
• CLINICAL APPLICATIONS: Late effects and survivorship

Prospective study

• Pain numeric rating scale (for pain right now) 
• Quality of life measured by The Uniscale
• Change in use of pain drugs
• Toxicity measured by the Cancer Therapy Evaluation Program, North Central Cancer Treatment Group Symptom Experience Diary

Fifteen of the 16 subjects reported a 20% reduction in their pain score by the end of the study. The pain score was reduced 59% from 5.81 pre-treatment to 2.38 at the end of the 10 days ( P < 0.0001 by paired t-test ). The daily reduction in pain score was 1.02 during the 10 days of treatment. After treatment was discontinued, pain scores returned to pretreatment levels. No changes in opioid doses occurred during the course of the study, with patients on average receiving 110-150 oral morphine equivalents per day. There were no changes in quality of life or symptoms (as evaluated by the Symptom Assessment Diary).

Although 15 of 16 patients experienced a reduction in their pain, drawing any significant conclusions is difficult with such a small sample in a prospective study.

• Small sample of less than 30
• Single site
• Not a randomized, double-blind study
• Short-term follow up period
• There was no discussion of changes in any non-opioid or coanalgesic medications for pain.
• Although the authors reported no changes in daily opioid intake during the study, it is not clear how this was determined.
• Changes in pain were measured only immediately pre- and post-intervention, so it is not clear if any effect occurred during the day other than immediately after the treatment.

MCA-5 therapy required patients to return to the clinic daily for 10 days post-treatment. This expectation may be impractical for many patients. Also, not all facilities would have someone available and skilled to do the procedure. The cost of the therapy could be an issue as well. Further research is needed to evaluate the potential benefits of this type of therapy, and longer term follow-up is needed. Consideration of background medications for pain in analysis of results is important for subgroup analysis. Research in this area using a sham-controlled procedure would be helpful to rule out placebo effect.

To examine the effects of therapeutic massage on pain, sleep quality, symptom distress, and anxiety in patients hospitalized for treatment of cancer

Patients who received massage had 15–20 minutes of light Swedish massage techniques of effleurage and petrissage three times during one week of hospitalization. Each session was given at least 24 hours apart. The control condition was 20 minutes of deliberate focused communication from a nurse. Discussions involved patient teaching, relaxation techniques, questions about cancer and treatment, life challenges, and stress reduction.

• The sample was 40 hospitalized patients with cancer.
• Mean patient age was 62 years; range was not provided.
• The sample was 95% male and 5% female.
• Various cancer diagnoses were included: lymph, lung, gastrointestinal, genitourinary, head and neck, leukemia, breast, and skin.
• The majority of patients were Caucasian, married or partnered, and not working.

• Single site
• Inpatient setting
• Colorado

Active treatment phase

A quasi-experimental design was used.

• Numeric Pain Rating Scale
• Verran and Snyder-Halpern Sleep Scale
• McCorkle Symptom Distress Scale
• Spielberger State-Trait Anxiety Inventory

• Analysis of variance showed changes in pain and symptom distress in the group receiving massage (p < 0.10), and in sleep in the control group (p < 0.10).
• There was no difference in anxiety.

Provision of therapeutic massage in hospitalized patients with cancer may have a positive effect on pain and symptom distress.

• The study had a small sample, with less than 100 participants.
• Because the study had no random assignment and no blinding, there is associated risk of bias.
• No information was provided on differences in use of pain medication or other interventions to control symptoms and relevant distress.
• The sample was biased, being mostly male and Caucasian.
• No information was provided about severity of illness.
• It is not clear whether the hospitalized patients were currently receiving chemotherapy or radiation therapy during hospitalization.

This study did not provide any strong support for the use of therapeutic massage in hospitalized patients with cancer.

A trained registered nurse (RN) provided 15 to 30 minutes of the light Swedish technique of effleurage and petrissage three times per week in the patients' hospital beds; sessions were 24 hours apart and at different times of the day and evening. The control group received 20 minutes of deliberate, focused communication. Outcomes were pain, sleep, symptom distress, and anxiety.

• The sample was comprised of 41 patients with cancer.
• Patients had leukemia, lymphoma, lung, gastrointestinal, genitourinary, head and neck, breast, and skin cancers.

• Inpatient
• Veteran’s administration hospital
• Midwestern United States

Patients were undergoing the active treatment phase of care.

The study used a quasiexperimental design, with pre- and postintervention comparison groups:  one arm received massage and the other was the control arm.

Verran and Snyder-Halpern Sleep Scale (VSH)

Sleep quality remained the same.

• The study had a small sample size and lacked random assignment to groups. Cohorts were treated sequentially.
• The sleep scale was not tested for validity and reliability with polysomnography.
• The RN must be trained in massage techniques.

To evaluate whether implantable drug delivery systems (IDDS) could help the most refractory patients failed by expert comprehensive medical management (CMM)

This was an RCT of IDDS (starting with morphine, but changing to a different drug if ineffective) plus CMM versus CMM alone in 200 patients with refractory cancer pain. Patients were randomized to CMM or IDDS. Clinical success was defined as a 20% reduction of pain regardless of toxicity or a 20% reduction of toxicity without a resulting increase in pain. A more stringent measure was a 20% reduction in both pain and toxicity. Results were obtained from weeks 4 and 12.

• N = 99 patients in the group (66 CMM only, 30 CMM plus IDDS)
• AGE: CMM only = 44–72 years; CMM plus IDDS = 32–69 years
• MALES: CMM only = 62.3 % males; CMM plus IDDS = 53.3% male
• KEY DISEASE CHARACTERISTICS: Patients had cancer. Cancers include lung, breast, prostate, colon, and pancreas.
• OTHER KEY SAMPLE CHARACTERISTICS: Patients had a visual analog scale (VAS) score of 5 or more despite pain management, were taking at least 200 mg oral morphine or equivalent, and had at least three months to live.

• RCT with crossover for clinical failure (pain 5 or more, limiting side effects, approved by investigator)

• VAS and National Cancer Institute Cancer Therapy Evaluation Program (CTEP) scales
• Composite drug toxicity score
• CMM measured by “Management of cancer pain: A quick reference guide for clinicians” (Agency for Health Care Policy and Research, 1994)

CMM patients who crossed to IDDS for the most refractory pain had a significant reduction in pain and drug toxicity. Patients who failed CMM and crossed to IDDS had a 27% reduction in pain scores and a 51% reduction in toxicity. Patients who failed CMM had a 20% reduction in pain, but pain was moderate to severe, while their opioid toxicity increased by 22%. Survival was improved in patients who received IDDS much earlier. Side effects and complications of IDDS were minimal, and there were no pump removals or infections.

Even the most refractory patients can have clinically important reductions in pain scores and drug side effects by crossing to IDDS. IDDS are shown to be comparable to other high-cost but effective cancer interventions. With refractory pain, the addition of IDDS to CMM can significantly improve pain management. A survival time of three months may be long enough for IDDS implant to be cost-effective.

• Small number of patients
• Question if improvement could be related to patients changing therapy when symptoms worsened, the Hawthorne effect, or placebo effect (implantation of a technological advanced device)
• Results may not be applicable to other centers with less experienced CMM or IDDS.

Studies need to look at the reason for improved survival with better pain control.

Determine the effect of duloxetine on pain severity

Patients were randomized to two study groups: group A subjects received 60 mg of duloxetine initially and then were crossed over to receive placebo and group B subjects initially received placebo and then were crossed over to duloxetine. The initial study period was five weeks. This was followed by a two-week washout period and then a final study period of an additional five weeks. Patients were assessed weekly. Use of other drugs that affect serotonin levels was not allowed. Concomitant use of other analgesics was allowed.

• N = 141
• MEAN AGE = 59 years (SD = 10.5 years)
• MALES = 37%, FEMALES = 63%
• KEY DISEASE CHARACTERISTICS: The majority of patients had gastrointestinal or breast cancer. All had received neurotoxic chemotherapy with taxanes or platinum compounds. 44% were considered high risk for peripheral neuropathic pain due to other conditions such as diabetes. All had at least grade 1 sensory pain on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v 3.0) and reported at least level 4 neuropathic pain on a 10-point scale for three or more months after completing chemotherapy.
• OTHER KEY SAMPLE CHARACTERISTICS: 81% were Caucasian; 14% were black.

• SITE: Multi-site 
• SETTING TYPE: Outpatient 
• LOCATION: United States

PHASE OF CARE: Transition phase after active treatment

Double-blind, placebo-controlled, crossover, randomized controlled trial

• Breif Pain Inventory (Short Form): Average pain severity was used as outcome.
• Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (Fact/GOG-Ntx)
• National Cancer Institute Common Terminology Criteria for Adverse Events (v 3.0)

Among patients who received duloxetine first, 59% reported some decrease in pain, 30% reported no change in pain, and 10% reported increased pain. Compared with placebo, there was a significant chance of receiving a 30% reduction in pain score (RR = 1.96, 95% CI 1.15-3.35) and a 50% reduction in average pain (RR = 2.43, 95% CI 1.11-5.30) with duloxetine. Analysis suggested a greater benefit in patients receiving platinums compared to those who received taxanes. Patients who received duloxetine in the second study period appeared to show greater reduction in average pain scores. Overall duloxetine treatment effect on pain was significant (p < .001). After initial treatment, 41% on duloxetine reported decrease in numbness and tingling in the feet versus 23% on placebo (p ≤ .05). This trend continued through the crossover period. In the duloxetine group, 11% dropped out due to adverse events, compared to 1% receiving placebo. More patients on duloxetine experienced nausea. Other adverse effects were similar between treatments. The most common adverse effects were fatigue and insomnia.

Compared to placebo, duloxetine treatment had a significant effect on pain from chemotherapy-induced peripheral neuropathy. Duloxetine also had some positive effect on numbness and tingling symptoms in the feet but not in upper extremities.

• Measurement validity/reliability was questionable.
• Subject withdrawals were ≥ 10%.
• Concomitant analgesics and changes in analgesics were not described.
• It is unclear why an apparent greater effect on average pain with duloxetine occurred in the second study period for group B. 
• There was an overall 19% drop-out rate.
• A higher proportion of grade 3 toxicities occurred with duloxetine.
• Only average pain, and pain interference during the initial study period, were compared, rather than comparison between the two study conditions. Why this was done is not clear..

Findings show that duloxetine can be effective in reducing pain from chemotherapy-induced peripheral neuropathy. Duloxetine also was associated with more adverse events. Nurses will need to monitor for adverse events, particularly for patients who may already be experiencing sleep wake disturbance and fatigue.

• FINAL NUMBER STUDIES INCLUDED = 13
• TOTAL PATIENTS INCLUDED IN REVIEW = 590
• KEY SAMPLE CHARACTERISTICS: The majority of the studies were of patients with diabetic neuropathy (7 of 13 were exclusively diabetic neuropathy; 8 of 13 were randomized, controlled trials; and 5 of 13 were quasiexperimental).

PHASE OF CARE: Late effects and survivorship

The variety of interventions and outcome measures made the pooling of data in this literature review difficult. Overall, very few randomized, controlled trials exist in this field. The authors described single study results throughout the study but did not pool the results; rather, they placed them in table. Each study was evaluated separately.

Some evidence supports the use of exercise to improve function in those with peripheral neuropathy. Exercise can improve function, balance, and gait for individuals with polyneuropathies and may delay the onset of peripheral neuropathy when administered long-term. For maximum effect, exercises or interval training were to be performed for 2–3 sessions per week with a minimum of 100 minutes of activity. Some of the exercise regimens may not be feasible in patients with cancer because of other side effects of therapy.

Study inclusion was stated but not exclusion. Only 13 studied were evaluated. No pooled data existed—too much heterogeneity. The information may not be useful in oncology because the majority of studies were of patients with diabetes or autoimmune neuropathy.

Nurses should focus further research on exercise in chemotherapy-induced peripheral neuropathy and should educate patients on symptoms and possible interventions for this side effect.

To describe the management of lymphedema in patients treated for head and neck cancer using complete decongestive therapy

This was a retrospective medical record review of patents evaluated and treated for lymphedema with head and neck cancer. Documented results were obtained at baseline and at the first evaluation after complete decongestive therapy (CDT). Patients had at least one training session for self-administration of manual lymph drainage, compression garments, skin care, and exercises for the face, neck,and oral cavity. Patients with severe lymphedema received two to five sessions of CDT with a therapist for two to four weeks as well as a daily self-administered home session, which was continued for as many as three months.

• N = 733  
• MEDIAN AGE = 61 years (range = 21–91 years)
• MALES: 79%, FEMALES: 21%
• KEY DISEASE CHARACTERISTICS: The most common tumor sites were the oropharynx, oral cavity, and larynx. The most common primary surgery prior to referral was total laryngectomy, and 54% of participants received lymph node dissections. The most common sites of edema were the neck and submental regions. Sixty-eight percent of patients had difficulty swallowing, 39% had difficulty breathing, and the majority had cosmetic concerns.

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

Retrospective, descriptive study

• Clinical evaluation using Foldi's Stages of Lymphedema Scale
• Measurements were summed to create a composite score.

The median time from the baseline assessment to follow-up was 69 days with a range of 9–371 days. Eighty-seven percent of patients reported at least partial adherence to self-administered home management. Overall, 60% of patients showed an improvement in lymphedema. Those who received therapist-administered sessions were more likely to show improvement at follow-up (72%) compared to those who only received the self-administered program (58%, p = 0.014). Those with the worst lymphedema demonstrated the most improvement.

CDT can be beneficial for the treatment of lymphedema in patients with head and neck cancer.

• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Measurement/methods not well described
• Measurement validity/reliability questionable
• Other limitations/explanation: There was no standard timing for the follow-up assessment and lymphedema measurement. The method of measurement was not sensitive or responsive enough to identify anything other than gross changes.

The measurement of lymphedema associated with head and neck cancer treatment is difficult. CDT has been shown to be effective in the management of lymphedema of the extremities, and this study suggests that it also is helpful for head and neck lymphedema. The differences among those who received therapist-delivered CDT versus those who did self-administered therapy are not clear because of measurement limitations, patient adherence, and other factors.

To determine the feasibility, acceptability, and safety of acupuncture to treat arm lymphedema in women following treatment for breast cancer

This was a randomized, controlled trial of acupuncture compared to usual treatment. Twenty women with stable, unilateral, intransient lymphedema that was present for at least six months prior were recruited. Ten participants were in the control group. The remaining 10 received 12 acupuncture treatments administered to body and arm points on the nonlymphedematous limb over eight weeks, twice weekly for four weeks then once weekly for four weeks. Clinical outcomes were assessed at baseline and again after eight weeks.

• N = 17  
• MEAN AGE = 57 years (control, SD = 8.4 years), 63.4 years (acupuncture, SD = 7.4 years)
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: Breast cancer-related lymphedema
• OTHER KEY SAMPLE CHARACTERISTICS: Had lymphedema for at least six months

• SITE: Single-site    
• SETTING TYPE: Outpatient    
• LOCATION: Clinic in Sydney, Australia

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

Randomized, controlled trial

• Bioimpedance spectroscopy (BIS) and arm circumference measure (SFB7 instrument)
• Lymphoedema Symptom Intensity and Distress Survey–Arm and Trunk (LSIDS-AT)
• Measure Yourself Medical Outcome Profile (MYMOP)

Compliance with the treatment protocol was high; 37 women were recruited and 20 were included in the trial. Three women withdrew from the trial. Participants reported an average of two symptoms associated with treatment. Acupuncture did not worsen lymphedema in the intervention group. The change in BIS measurements ranged from a 0.01 increase to a 0.3 decrease in the control group. The intervention group’s BIS measurements saw an increase of 0.28 and a decrease or 0.43. No increases in swelling greater than 10% occurred. No changes in quality of life or other patient-reported outcome measures related to lymphedema were reported.

Acupuncture did not cause any significant changes in limb volume for women with arm lymphedema. It may stabilize lymphedema symptoms. No major safety concerns were identified.

• Small sample (< 30)
• Key sample group differences that could influence results
• Subject withdrawals ≥ 10%
• Other limitations/explanation: The control and intervention groups were chosen randomly, but the women in the acupuncture group had symptoms for a significantly longer period of time.

Acupuncture did not improve or exacerbate lymphedema in women who were breast cancer survivors. At this time, there is not enough research to promote the use of acupuncture as an effective intervention for the reduction of arm volume in this population.

RESOURCE TYPE: Evidence-based guideline

PHASE OF CARE: Active antitumor treatment

Sixty-six publications formed the evidence base for the recommendations. Forty-one were randomized, controlled trials.

• Secondary CSF prophylaxis is recommended for patients who have a neutropenic complication from a prior cycle of chemotherapy.
• CSFs should be administered after an autologous HCT (strong recommendation) and may be administered after allogeneic hematopoietic cell transplantation (HCT) (weak recommendation).
• The use of CSFs as primary prophylaxis in children is reasonable.
• Prophylactic CSF for patients with aggressive lymphoma aged 65 and older undergoing curative treatment should be provided (moderate strength recommendation).

The guidelines provide general recommendations for the primary and secondary prophylactic use of CSFs in patients being treated for cancer, and also outlines concerns regarding cost and the potential overuse of CSFs. The determination of a 20% risk for febrile neutropenia was not straightforward given patient variation and regimen alterations according to individual patient responses. Further work is needed to develop and evaluate clear individualized risk-based models for CSF use in a variety of patients with cancer.

To evaluate the feasibility and acceptability of acupuncture in managing fatigue and well-being in women with breast cancer.

Patients were randomized to acupuncture, sham control, or wait-list control groups. Six acupuncturists provided the interventions. All needles were inserted with a Park device for both the sham and actual groups. Treatments were performed twice weekly for three weeks and then weekly for another three weeks. Acupuncture was administered at five points, and the needles were stimulated manually. Needles were retained for a maximum of 20 minutes, and sessions lasted 45 minutes. Women in the wait-list control were contacted every four days during the study. Women in the acupuncture group were also interviewed to explore the perceived impact of the intervention.

• In total, 30 patients (100% female) were included.
• Mean age was 55 years.
• All patients had breast cancer.
• No patients were receiving treatment during the study.
• Prior treatments received were not described.
• All patients had fatigue scores between 4 and 6, which were considered moderate levels at baseline.

• Single site  
• Outpatient 
• Australia

• Patients were undergoing the transition phase after active treatment.
• The study has clinical applicability for palliative care.

The study used a randomized, sham-controlled trial, with a mixed method.

• Brief Fatigue Inventory (BFI)
• Well-Being Questionnaire (W-BQ12)
• Measure Yourself Concerns and Wellbeing Questionnaire (MyCaW)

Fatigue declined over time in all three groups. It was reported that fatigue declined significantly in the acupuncture group after two weeks; however, no statistical results were provided. Almost half of the women recruited declined participation, mainly due to the travel distance required. Well-being scores improved in all women, with no differences between groups. Findings from interviews showed that women who received acupuncture experienced improved sleep and relaxation with treatments and improved mood.

Findings suggested that acupuncture treatment is feasible in this group of patients and may be of benefit in improving fatigue.

The study had a small sample size, with less than 100 patients.

The study suggested that acupuncture was feasible as provided and might have benefit in the management of fatigue; however, the study did not provide strong evidence to support the efficacy of acupuncture to improve fatigue.