To evaluate whether a topical menthol product has clinical benefit for pain of peripheral neuropathy

Patients were given a 1% menthol in aqueous cream and were instructed how to apply it to the affected area and corresponding dermatome region of the spine twice daily. Patients were followed for four to six weeks.

• N = 40  
• MEAN AGE = 61 years
• AGE RANGE = 20–89 years
• MALES: 37%, FEMALES: 63%
• KEY DISEASE CHARACTERISTICS: Patients had chronic neuropathic pain: 80% had chemotherapy-induced peripheral neuropathy diagnosed by a physician, and 20% had scar pain related to treatment for breast cancer. Breast and colon cancers were the most common. 
• OTHER KEY SAMPLE CHARACTERISTICS: Median of 11 months since chemotherapy treatment

• SITE: Single site   
• SETTING TYPE: Outpatient    
• LOCATION: United Kingdom

PHASE OF CARE: Late effects and survivorship

Open-label

• Brief Pain Inventory-Short Form (BPI-SF)
• Hospital Anxiety and Depression Scale (HADS)
• Leeds Assessment of Neuropathic Symptoms and Signs (LANSS)
• Walking ability: GAITRite mat to measure velocity and cadence
• Hand dexterity
• Quantitative sensory testing (QST)

Eighty-two percent showed an improvement in pain scores (p < 0.001). Significant improvements were observed in some aspects of quantitative sensory testing for mechanical detection threshold, cool stimulus, and warm stimulus. Both walking velocity and cadence improved. No significant changes in hand dexterity or LANSS scores were reported.

The findings suggest that the topical application of menthol can improve symptoms of chronic chemotherapy-induced peripheral neuropathy.

• Small sample (< 100)
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Subject withdrawals ≥ 10%

This study is limited by its small sample size and study design, but shows promising proof of concept results related to molecular receptors in sensory nerves that appear to respond to topical menthol. Very few interventions have been shown to prevent or effectively treat chemotherapy-induced peripheral neuropathy, so further research on the use of topical menthol is warranted. Further well designed studies are needed.

To determine the effectiveness of pregabalin in conjunction with radiotherapy to treat patients with cancer-induced bone pain (CIBP)

This double-blind randomized study examined the concurrent use of pregabalin with palliative radiotherapy (versus placebo with radiotherapy) to prove the efficacy of use for treatment of CIBP. Patients were given 75 mg pregabalin or placebo twice daily for 35 days. Assessment of analgesia was done every seven days from baseline. If adequate analgesia was not achieved, trial medication was increased incrementally up to 300 mg twice daily. Radiotherapy was given in either one fraction of 8 GY or 20 Gy in five fractions.

• N = 233   
• AGE:18 years or older; more than 95% of participants were 45 years or older
• MALES: 50.9% pregabalin, 60.7% placebo; FEMALES: 49.1% pregabalin, 39.3% placebo
• CURRENT TREATMENT: Radiation 
• KEY DISEASE CHARACTERISTICS: Those with radiologically proven bone metastases who were scheduled to receive radiotherapy as pain treatment and who had pain scores equal to or greater than 4 on the 0–10 pain scale
• OTHER KEY SAMPLE CHARACTERISTICS: Participants had a life expectancy greater than two months, one or more sites of CIBP being treated with radiotherapy, the ability to provide informed consent to participate in the trial, and did not currently use gabapentin and/or pregabalin in therapeutic regimen (in other words, participation in this study would be the introduction of pregabalin in those participants, not in the placebo arm). Patients who had any change in cancer treatment therapy before entering the study (with the potential to influence pain perception) were excluded.

• SITE: Multicenter
• SETTING TYPE: Outpatient
• LOCATION: Five cancer centers in the UK

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

• Multicenter, double-blinded randomized trial

• 0-10 Numeric Rating Scale
• Brief Pain Inventory (BPI) for worst pain and pain interference
• Hospital Anxiety and Depression Scale (HADS)

No statistically significant differences in average pain, pain intereference, or quality of life were discovered. However, differences in mood and breakthrough pain duration, which was lesser in the pregabalin arm (p = 0.037), were present.

These findings do not support use of pregabalin in patients with CIBP receiving palliative radiotherapy.

• Optimal dose of pregabalin was not determined prior to the study.
• No subgroup analysis based on fractionation/schedule of radiotherapy
• No information regarding any use of bone-modifying agents

Nurses providing care to patients in the outpatient setting are in prime position to conduct further research to determine the efficacy of adjunct medications and/or other treatment modalities used for treatment of CIBP and chronic cancer pain in general. Nurses may serve as principal investigators or coinvestigators in further research to determine the most effective interventions. Nurses may also serve to make recommendations for Putting Evidence into Practice (PEP) in outpatient cancer treatment settings, and in doing so serve as patient advocates. Findings do not support the use of pregabalin for metastatic bone pain in patients with cancer.

To compare the efficacy and tolerability of fentanyl-pectin spray (FPNS) with that of immediate-release morphine sulfate (IRMS) in the treatment of breakthrough cancer pain (BTCP)

Patients in the study were experiencing 1–4 episodes of BTCP per day while taking at least 60 mg/day of oral morphine or equivalent for BTCP. Patients completing the titration phase continued to the double-blind, double-dummy phase: 10 episodes of BTCP were randomly treated with FPNS and oral capsule placebo (5 episodes) or IRMS and nasal spray placebo (5 episodes). The primary end point was pain intensity (PI) difference from baseline at 15 minutes. Secondary end points were onset PI decrease (≥ 1 point) and time to clinically meaningful pain relief. Safety and tolerability were evaluated by means of adverse events (AEs) and nasal assessments. By-patient and by-episode analysis were completed. Duration of follow-up was a maximum of 14 days in the open-label period.

• The sample was composed of 110 patients.   
• Mean patient age at baseline was 55.9 years (SD = 12.3 years). Of all patients, 65.1% were 60 years old or younger.
• Of all patients, 53.8% were male and 46.2% were female.
• All patients received fixed-schedule opioid regimens consisting of a total dose equal to or greater than 60 mg/day oral morphine for BTCP. All patients had 1-4 episodes per day of BTCP.
• Exclusion criteria barred participation of patients
  • With uncontrolled or rapidly escalating background pain.
  • Who were medically unstable.
  • Who had breakthrough pain unrelated to cancer.
  • With a past inability to tolerate fentanyl or other opioids.
  • Who anticipated receiving therapy with any pain-affecting treatment (i.e., radiotherapy, chemotherapy) during the study or who had received treatment with another investigational drug within 30 days.
  • With any disorder or using any medication likely to adversely affect normal functioning of the nasal mucosa.

• Multicenter (35 oncology centers)
• Europe and India
   

• Phase of care: active treatment
• Clinical application: palliative care

Randomized, controlled, double-blind, double-dummy, multiple crossover trial

• 11-point numeric scale (0 = no pain, 10 = worst possible pain), to measure pain intensity.
• Nasal assessments performed by the study physician.
• Four-point scale (0 = absent, 3 = severe) of subjective nasal assessment by the patient, who completed a 10-item questionnaire before the first use of the study drug, one hour after each dose of the study medication, and at the final study visit. Items rated included stuffy/blocked nose, runny nose, itching/sneezing, crusting/dryness, burning/discomfort, nosebleed, cough, postnasal drip, sore throat, and taste disturbance.
   

• Analysis of pain intensity difference pre- and post-treatment showed that FPNS provided a greater reduction in pain intensity than did IRMS, with mean ± SE 3.02 ± 0.21 for FPNS doses and 2.69 ± 0.18 for IRMS (p < 0.05). Statistical superiority of FPNS compared with IRMS, on patient-averaged PID scores, continued at each point 15–60 minutes (p < 0.05).
• After treatment, from 10 minutes onward, mean PI scores were lower for FPNS-treated episodes than for IRMS-treated episodes.
• More treatment-emergent AEs occurred after FPNS than after IRMS treatment. A higher percentage of treatment-emergent AEs occurred after 400 mcg and 800 mcg doses of FPNS. Treatment-emergent AEs were mainly mild to moderate in severity and included vomiting, somnolence, dehydration, and nausea. Of all patients, 4.7% of patients withdrew from titration due to AEs.
   

The pain intensity difference associated with FPNS was greater than that associated with IRMS. The difference between the two measures of pain intensity was statistically significant (p < 0.05).

• The study was of short duration, only 14 days. This period is not long enough to evaluate potential long-term effects on the nasal mucosa.
• The study design did not include titration to an effective dose of IRMS.

For patients receiving around-the-clock opioid treatment for chronic cancer-related breakthrough pain, FPNS appears to be effective, safe, and well tolerated. The early reduction of pain that FPNS provided either matched or exceeded that provided by IRMS. Compared to IRMS, FPNS provided more complete pain relief. The effects of long-term use of FPNS have not been evaluated; nurses must be aware that long-term effects of FPNS on the nasal mucosa are unknown.

To determine if sucralfate has a role in the prevention of radiodermatitis. A 1% concentration of sucralfate in lotion was tested.

Several zones on the breast were laid out by the investigators, with one zone in the irradiated field left untreated, one with sucralfate, and one that was not within the field of radiation therapy (RT). All patients were instructed to apply sucralfate lotion twice a day, one to two hours prior to treatment and within two hours after RT.

• The sample was comprised of 21 women with breast cancer.
• Median age was 58.3 years.
• Patients were receiving no concomitant chemotherapy treatment.
• The treatment dose was 45 Gy.

Unspecified

The study used a quasiexperimental design—patients were used as their own controls.

• Spectrophotometry was used to measure the response of skin on all zones compared to the zone that was not within the field of RT. Differences between the control radiated zone and the control zone that was not within the field of RT were analyzed. Changes in brightness and skin tonality were used to indicate the degree of erythema.
• Radiation Therapy Oncology Group (RTOG) acute skin toxicity scale
• Patients were evaluated once a week at 10 Gy, 20 Gy, 30 Gy, 40 Gy, and 50 Gy.
• Additional variables included prior surgery, tumor location, prior chemotherapy, skin phototype, other cutaneous diseases, and systemic diseases.

• Skin became darker and redder by spectrophotometry with irradiation for all patients, with maximum skin response at weeks 4 and 5.
• No differences existed in redness between sucralfate-treated and untreated areas.
• Six patients had skin reactions between weeks 4 and 5 that were graded I and II on the RTOG scale.
• Researchers suggested that the use of spectrophotometry was more effective than the RTOG scale for evaluation of skin changes.

No radioprotective effect was demonstrated with sucralfate.

• The study had a small sample size.
• The authors did not state who did the rating/skin examination, and actual RTOG scale results were not reported.
• Other studies have used a higher concentration of sucralfate (7%).

To evaluate whether paravertebral block use affected opioid use, antiemetic use, and length of stay in patients receiving mastectomies

Patient data were collected from medical records from the time periods before and after the use of paravertebral blocks (PVBs). Patients receiving unilateral mastectomies had unilateral PVBs, and those receiving bilateral mastectomies had bilateral PVBs. Blocks were placed preoperatively. All patients had general anesthesia. Prophylactic opioids and antiemetics were given intraoperatively at the discretion of the anesthesia team. Pain scores were documented with vital sign monitoring postoperatively. The results of those who had PVBs were compared to a cohort of patients who did not have PVBs.

• N = 526  
• MEAN AGE = 56.5 years (range = 20–97 years)
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: All had breast cancer, and slightly less than half had unilateral mastectomy; about half had immediate reconstruction
• OTHER KEY SAMPLE CHARACTERISTICS: 75% did not have axillary lymph nodes removed

• SITE: Single site  
• SETTING TYPE: Inpatient    
• LOCATION: Rochester, NY

• PHASE OF CARE: Active antitumor treatment

Retrospective cohort comparison

• Total postoperative opioid consumption
• Length of stay less than or greater than 36 hours
• Length of time in the postanesthesia care unit

In a multivariate analysis that was controlled for age and surgeon, there was no significant difference between groups in length of stay. The percentage of patients requiring antiemetics was higher in the no-PVB group (57 versus 39%, respectively, p < 0.00001). The amount of opioids required was higher in the no-PVB group on the day of surgery (47.6 versus 40.1 morphine equivalents, respectively, p < 0.0001). Despite differences in opioid consumption, there were no significant differences between groups in pain scores. The greatest difference in opioid consumption was seen in patients receiving immediate bilateral reconstructions.

The use of PVBs in patients receiving mastectomies was associated with lower antiemetic and opioid consumption on the day of surgery.

• Risk of bias (no random assignment)
• Key sample group differences that could influence results 
• Measurement/methods not well described 
• Other limitations/explanation: The method of pain measurement and the actual timing of measurement was not described. It appeared that the analysis was done in terms of opioid consumption for only the day of surgery. The analysis did not take into account any prophylactic antiemetics or opioids given intraoperatively. No description or standardization of all relevant postoperative medications was given.

The findings of this study suggested that among patients receiving mastectomies, PVBs may reduce the need for postoperative antiemetics and opioids. However, it was not clear that the procedure actually reduced postoperative pain. This procedure appeared to be most beneficial for women having the most extensive surgical procedures. Additional well-designed research is warranted to determine the clinical benefits of PVB and its role in improving perioperative pain control.

Evaluate effectiveness of pyridoxine for treating PPE in patients with metastatic colon cancer who are receiving continuous 5-FU

Patients were treated with 5-FU 200 mg/m² by continuous infusion (CI) until moderate to severe toxicity developed.

Five previously untreated patients who developed PPE were given oral pyridoxine (50 or 150 mg every day) when moderate PPE changes were noted.

Study conducted between September 1984 and July 1986.

N: 25

KEY DISEASE CHARACTERISTICS: Patients with metastatic colon cancer receiving continuous 5-FU infusion (200–300 mg/m²/day).

SITE: Multi-site

LOCATION: University of Kansas Medical Center; Fred Hutchinson Cancer Research Center

• Non-randomized, non–double-blinded, uncontrolled study

Skin toxicity was graded as follows.

• 0 = Normal
• 1 = Numbness, nail changes, painless swelling, or erythema
• 2 = Painful erythema with or without swelling
• 3 = Moist desquamation

PPE developed in 16 of the 25 patients. The five previously untreated patients who developed PPE received 50 or 150 mg of oral pyridoxine per day when moderate PPE changes were noted. Reversal of PPE without interruption of 5-FU was seen in four out of five patients, and these patients continued 5-FU for a median of six months after developing PPE.

Oral pyridoxine may reduce incidence and severity of PPE symptoms associated with 5-FU continuous infusion.

• Small sample size
• Not randomized and not double-blinded
• Inadequate description of measurement tool/method to grade PPE symptoms

To test the efficacy and safety of two different schedules of ondansetron as rescue antiemetic treatment in patients who were refractory to standard antiemetic prophylaxis for delayed emesis following moderately emetogenic chemotherapy (MEC)

Patients were randomly allocated to one of two treatment groups for rescue antiemetic treatment: intramuscular ondansetron 8 mg or oral ondansetron 16 mg for days two to six (antiemetic prophylaxis was provided by ondansetron 8 mg IV plus dexamethasone 8 mg IV for acute emesis and dexamethasone 8 mg for four days for delayed emesis).

• The sample consisted of 89 participants.
• In the intramuscular ondansetrong group, the average patient age was 58 years with a range of 27–83 years. In the oral ondansetron group, the average age was 61 years with a range of 28–79).
• The sample was 85.4% female and 14.6% male.
• The majority had breast, lung, and gynecologic cancers.
• Patients received either an anthracycline chemotherapy regimen (highly emetogenic chemotherapy [HEC], MEC), a carboplatin regimen, or an irinotecan/oxaliplatin regimen.

The study was conducted at a single site, outpatient setting.

All patients were in active treatment.

The study design was a prospective trial (open label, phase II, randomly assigned to treatment group).

• Participants recorded in diaries the dates and times of emetic episodes, severity of nausea or vomiting, use of rescue treatment, and efficacy of treatment (absence or presence of further emetic events).
• Participants also rated their personal satisfaction with the assigned rescue medication (satisfied, partially satisfied, unsatisfied).
• The Common Terminology Criteria for Adverse Events (NCI-CTCAE. V. 3.0) was used.

Oral ondansetron 16 mg was significantly superior to intramuscular ondansetron 8 mg for nausea and vomiting control during days two to six (p < 0.01). The two arms had a similar adverse event profile. A higher degree of personal satisfaction was found with oral ondansetron.

Because of its high efficacy and excellent tolerability, oral ondansetron is an important option in the management of MEC-related delayed emesis refractory to standard antiemetic prophylaxis.

• The sample was small with fewer than 100 participants.
• No control group was included.
• The frequency of the use of rescue medication was not reported, which may have contributed to the study results (ease of access to phone orders may have contributed to better efficacy and more satisfaction.)
• Interpretation of results as a pure difference between orodispersible ondansetron and intramuscular ondansetron is difficult.

The oral form of ondansetron could provide satisfactory rescue for breakthrough delayed emesis when compared to the Intramuscular form of ondansetron, with a similar adverse event profile.

Patients were randomly assigned to the control group (usual antiemetic protocol) or experimental group (usual antiemetic protocol plus music intervention during the 48 hours of high-dose cyclophosphamide administered as part of the preparative regimen for autologous or allogeneic bone marrow transplantation). The experimental group listened to self-selected music (by portable compact disc players and headphones) for 45 minutes at 6, 9, and 12 hours after the start of each infusion as an adjunct to antiemetic therapy.

• The sample consisted of 39 patients, but 33 were included in data analysis.
• The experimental group had 11 males and 5 females; the control group had 8 males and 9 females.
• The median age was 40.3 years for males and 36.9 years for females.
• Race and ethnicity were not reported.
• Treatment was autologous or allogeneic bone marrow transplantation, with high-dose preparative regimens. Participants were inpatients.

The study was conducted at a comprehensive cancer center in the midwestern United States.

The study design was a randomized, controlled clinical trial.

• Nausea was measured at baseline and every eight hours using a visual analog scale (VAS) in the form of a thermometer (0–100 in five-degree increments).
• Nausea was measured the with “feel bad” scale, a five-point, Likert-type scale describing how bad the nausea felt or how sick to the stomach the patient was. Subjective feelings of nausea and all episodes of vomiting were recorded.

Significant differences were found between scores on the VAS for nausea and number of episodes of vomiting; less nausea and fewer instances of vomiting were reported in the experimental group.

Music as an adjunct to antiemetic therapy for chemotherapy-induced nausea and vomiting with high-dose chemotherapy can be effective.

• Only bone marrow transplant recipients were included, one site was used, and the sample size was small.
• The study was a longitudinal study; therefore, problems existed with multiple data collection points, resulting in some missing data.
• Compliance issues existed regarding the music intervention. Patients did not always want to listen to music at designated times because they did not feel well or visitors were present.

• FINAL NUMBER STUDIES INCLUDED = 6
• TOTAL PATIENTS INCLUDED IN REVIEW = 208
• KEY SAMPLE CHARACTERISTICS: All trials included MLD with some form of compression. These were placed into three categories, (a) MLD with standard physiotherapy versus standard physiotherapy, (b) MLD with compression bandaging versus compression bandaging, or (c) MLD with compression therapy versus nonmanual lymphatic drainage treatment with compression therapy 

PHASE OF CARE: Late effects and survivorship

1. MLD with standard physiotherapy versus physiotherapy: This method demonstrated improvements in both groups, but no significant differences were seen between the two.
2. MLD with compression bandaging versus compression bandaging alone: A significant percentage in reductions were seen for bandaging alone with an additional 7.11% reduction with MLD. Significant analyses showed that participants with mild to moderate BCRL responded better to MLD than participants with more severe swelling.
3. MLD with compression therapy versus nonmanual lymphatic drainage treatment with compression therapy: Too varied

1. Volumetric changes in arm, hand, or trunk indicated that more research should be done to identify the most clinically meaningful volumetric measurement.
2. The functional outcome of range of motion showed contradictory results.
3. Quality of life outcomes were inconclusive or not measured in all, and in two trials that measured this outcome, one did not report the results. Future research should use a lymphedema-specific quality of life tool.

• MLD is safe and may offer an additional benefit to bandaging for fluid reduction.
• More studies are needed to confirm which stage of lymphedema benefits most from the addition of MLD.
• Studies should include a lymphedema-specific quality of life tool and functional outcomes.

• Trials were limited in size and participants
• Potential bias in four trials as person measuring swelling knew what treatment participants were receiving
• All trials assessed phase 1 decongestion, but only one also looked at phase 2 maintenance.

Nurses need to provide early identification and education to affect patients' lymphedema treatment. MLD is a safe component of lymphedema therapy. Long-term adherence to treatment and garments are needed maintain reductions in swelling.

Database searched was MEDLINE (1966-Dec 2003).

Search keywords were acupuncture, alternative medicine, electroacupuncture, moxibustion, “injections, intramuscular”, “Medicine, Traditional Chinese”, acupressure, transcutaneous electrical nerve stimulation (TENS), and TENS. These were combined with nausea, vomiting, emesis, antiemetic therapy, and antineoplastic agents/adverse effects.

Studies were included in the review if they

• Were randomized.
• Involved patients receiving chemotherapy.
• Included an intervention that stimulated acupuncture points.
• Reported on nausea or vomiting as outcomes.

Studies were excluded from the review if they had a high possibility of bias.

In all, 14 studies were identified and reviewed.

In the nine studies that evaluated acute vomiting management via acupuncture-point stimulation, acute vomiting was reduced but nausea severity was not.

In the seven studies that assessed acute nausea via acupressure, acute nausea severity was reduced.

Three studies that evaluated delayed vomiting did not support the intervention.

In the five studies using acupuncture-point stimulation, the intervention did not reduce delayed vomiting.

The pooled results of 11 studies using acupuncture-point stimulation plus antiemetics for chemotherapy-induced nausea and vomiting (CINV) showed significant reduction in acute vomiting and marginal statistical significance for reducing acute nausea.

Electroacupuncture provided protective effects for acute vomiting, but acupuncture did not. Acupressure was effective for acute nausea in patients using “state-of-the-art” antiemetics. However, placebo effects may have influenced results.