To evaluate the safety and initial efficacy of acupuncture for the treatment of thalidomide and bortezomib-induced chronic peripheral neuropathy (PN)

Standardized acupuncture medication and equipment was used by two licensed acupuncturists three times per week for four weeks (one week of rest; two times per week for four weeks). Both upper extremities and both lower extremities had the same point sites of treatment. After participants experienced a sensation of numbness, tingling, or warmth at the needle insertion site, an electrical stimulation was applied bilaterally for 20 minutes after completion of 80% of treatment sessions.

• N = 19  
• AGE RANGE = 46–79 years
• MALES: 74%, FEMALES: 26%
• KEY DISEASE CHARACTERISTICS: Multiple myeloma 95%; amyloidosis 5%; for peripheral neuropathy (PN), all patients had symptoms in upper and lower extremities
• OTHER KEY SAMPLE CHARACTERISTICS: PN treatment, pain management, and prior therapy were allowed. Dose ranges and the number of months since last dose were recorded. Participants had Eastern Cooperative Oncology Group statuses < 2. Patients were allowed to remain on the same medication regimens for PN and pain. Minor adjustments to medications were allowed.

• SITE: Single-site
• SETTING TYPE: Outpatient
• LOCATION: MD Anderson Cancer Center in Houston, TX, United States

• PHASE OF CARE: Active antitumor treatment
• APPLICATIONS: Elder care, palliative care

Nonrandomized, pilot feasibility, safety and efficacy study with a quasi-experimental design

The National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) were used to evaluate for PN prior to beginning the study. The General Functional Assessment of Cancer Therapy (FACT-G) and the Brief Pain Inventory Short Form (BPI-SF) were used to evaluate patient-reported outcomes and baseline and at weeks 4, 9, and 13 during the study. Objective measurements (coin test, button test, walking test, postural stability/fall risk) and bilateral tibial and sural sensory nerve conduction tests were conducted at baseline and at week 13. The FACT and Gynecologic Oncology Group-Neurotoxicity (GOG-NTX) scales were used to assess the primary thee endpoints for PN at baseline and at weeks 4, 9, and 13. Evaluable patients completed 80% of the study medication.

BPI-SF scores significantly improved in regard to pain severity with the worst pain occurring at 24 hours at all time points with large effect sizes in weeks 9 and 13. There was a significant improvement in BPI-SF pain interference in weeks 9 and 13 with a moderate effect size. FACT and GOG-NTX scores showed significant improvement in weeks 4, 9, and 13. Timed motor function tests from baseline to one month after the beginning of the study showed significant improvement. There was no statistically significant difference for fall risk, and nerve conduction studies demonstrated no change.

This feasibility, safety, and efficacy trial of electroacupuncture in 19 patients experiencing bortezomib- or thalidomide-induced PN demonstrated significant improvements in patient-reported outcomes for pain severity and interference according to the BPI-SF, FACT and GOG-NTX scores, and objective timed motor function tests from baseline to 13 weeks. No safety issues were reported.

• Small sample (< 30)
• Baseline sample/group differences of import
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Risk of bias (sample characteristics)
• Unintended interventions or applicable interventions not described that would influence results
• Key sample group differences that could influence results
• Measurement/methods not well described
• Measurement validity/reliability questionable
• Findings not generalizable
• Treatment group differences: Previous medications were 84% bortezomib versus 16% thalidomide. 68% of patients experienced grade 2 PN while 32% experienced grade 3 PN. At baseline, PN occurrences were 74% male and 26% female. 58% of patients were taking pregabalin and 32% were taking gabapentin; 41% of patients were taking opioids. The frequency of pain medication use during treatment was not measured. The nerve conduction studies that were performed were not reported. The method of assessment was not well described. The reliability and validity of tools was not reported.

The use of electroacupuncture requires additional study in large, randomized, controlled trials to establish safety, benefits, the duration and sustainability of benefits, and treatment recommendations as an adjunct therapy for bortezomib- and thalidomide-induced PN.

To evaluate the effectiveness of acupuncture for symptom control in patients with cancer.

Databases searched were MEDLINE, EMBASE, CINAHL, Cochrane Collaboration, Scopus, and PubMed through December 2011.

Search keywords were acupuncture, electroacupuncture, moxibustion, Chinese medicine, Asian medicine, and keywords that included cancer and cancer symptoms.

Studies were included in the review if they

• Were randomized, clinical trials (RCTs)
• Involved acupuncture with needle insertion
• Compared acupuncture to control, placebo, or sham acupuncture.

Studies were excluded from the review if they

• Compared two active acupuncture forms, acupressure, or other interventions similar to acupuncture that did not involve needle insertion
• Did not measure the effect of acupuncture on symptoms
• Were considered gray literature (i.e., not generally accessible).

In total, 3,494 references were retrieved and evaluated according to the Cochrane Handbook for Systematic Reviews of Interventions.

• The final number of studies included was 41.
• The authors did not provide the sample range across studies, total number of patients, disease types, or characteristics.

Studies addressed potential management of the following symptoms:

• Pain:  Eleven RCTs met the criteria for analysis. No large trials reported positive results or were of good quality.
• Chemotherapy-Induced Nausea and Vomiting (CINV):  Eleven RCTs met the criteria for analysis. One large study with a low risk of bias showed between-group effect sizes for acupuncture versus sham (0.80) and for acupuncture versus usual care (1.10).
• Fatigue:  Three RCTs met the criteria for analysis. All had high risks of bias, and two had negative outcomes.
• Hot Flashes:  Seven RCTs met the criteria for analysis. None had a low risk of bias.
• Anxiety or Depression:  Five of the six RCTs analyzed showed positive results. All five had high risks of bias.
• Sleep:  Three RCTs met the criteria for analysis, and all three reported positive outcomes and had high risks of bias.

The strongest evidence that the study produced showed that acupuncture may be effective for the management of CINV. The study did not show acupuncture to be efficacious in the treatment of other symptoms.

The studies included were of low quality.

Available evidence, which was limited, did not support the claim that acupuncture is effective in alleviating various adverse symptoms in adults with cancer. Additional research is needed to determine the efficacy. The findings of this analysis suggested that patients with uncontrolled CINV may be appropriate candidates for acupuncture referral. For the treatment of other symptoms, the efficacy is undetermined.

To test the hypotheses that acupuncture would be feasible, safe, and effective adjunct for pain management

Patients were recruited from referrals to a pain management center. Patients received individualized acupuncture treatments one to three times per week. Treatments were provided by two licensed and experienced acupuncturists. The points used in the treatments are described, and standard techniques for point location were used. Needles were left in place for about 25 minutes. Electrical stimulation was added at the discretion of the practitioner. Study measures were obtained at baseline and after the last acupuncture session. Patients were dropped from the analysis if pain control medications were changed during the course of the study.

• N = 41  
• MEAN AGE = 54 years (range = 33–88 years)
• MALES: 29%, FEMALES: 71%
• KEY DISEASE CHARACTERISTICS: Multiple tumor types (breast was most common); patients had varied stages of disease
• OTHER KEY SAMPLE CHARACTERISTICS: Pain scores were > 4 on a numeric rating scale at study entry, and mean duration of pain management we 31 months. There were varied locations of pain with low back, neck, and shoulder being the most common. Most patients had multiple locations of pain.

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

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

Single-arm prospective trial

• Brief Pain Inventory (BPI)
• MD Anderson Symptom Inventory (MASI)

The average number of treatments was eight (range = 2–10) over five weeks excluding drop-outs. 71% of patients received auricular acupuncture and 71% received electroacupuncture. Pain severity and interference scores declined significantly (p < .0011) using the BPI. A significant reduction in both of these aspects was also seen with the MASI (p < .002). Intent-to-treat analysis using the replacement of missing values with group means showed the same results. For 44% of patients, pain medications remained the same as those at baseline. Fewer patients required opioids at follow-up compared to baseline, and the prevalence of use of other medications for pain such as nonopioid analgesics, antidepressants, and other adjuvant medications declined. 87% of patients stated that the course of acupuncture treatment met their expectations very or extremely well. There were no adverse effects of acupuncture reported.

Findings suggest that the use of acupuncture as an adjunctive therapy for chronic pain management is feasible, is safe, and can be beneficial in reducing pain.

• Small sample (< 100)
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Unintended interventions or applicable interventions not described that would influence results
• Subject withdrawals ≥ 10%  
• Other limitations/explanation: Although it was stated that patients were not to have pain medication changed during the study, substantial changes in various medications occurred and were reported. There was a 21% drop-out rate with about 40% of these due to changes in pain medication.

Findings suggest that acupuncture treatment as an adjunctive pain management approach can be beneficial for some patients. Interpretation of findings is difficult due to the individualization of the treatment regimen, study design limitations, and the likelihood that there is a placebo effect with acupuncture. For those patients who wish to try acupuncture for pain management, it appears to be feasible and safe when provided by appropriate practitioners.

PURPOSE: To synthesize evidence regarding the effectiveness of education for decreasing anxiety in patients receiving chemotherapy for the first time

• FINAL NUMBER STUDIES INCLUDED = 10 articles
• TOTAL PATIENTS INCLUDED IN REVIEW = N/A (not all resources included were research studies or systematic reviews)
• SAMPLE RANGE ACROSS STUDIES: N/A
• KEY SAMPLE CHARACTERISTICS: Three references were related to patients receiving chemotherapy for the first time. Other references included general practice guidelines and expert opinions.

PHASE OF CARE: Active antitumor treatment

Three sources were guidelines, two were pilot studies, one was an evidence summary review, one was a systematic review, and one was an expert opinion. Most sources were of poor or fair quality. Not all the studies actually measured anxiety; some measured patient satisfaction. There was no differentiation made between the provision of educational and informational written materials and the provision of psychoeducation or cognitive behavioral therapy interventions.

This review provides minimal actual evidence regarding the effectiveness of educational interventions.

A limited number of actual studies were included, and those included did not all address or measure anxiety.

Patient education prior to receiving chemotherapy is an essential aspect of patient care in providing an informed and empowered patient. The impact of education alone on anxiety is not clear, and this article does not provide substantial evidence or synthesis to clarify this potential effect of educational interventions.

To evaluate the effects of anamorelin in patients with cancer-related cachexia

Patients received anamorelin 50 mg/day or placebo for a three-day treatment period. This was followed by a seven-day washout period. After the washout, patients were switched to the opposite intervention. Assessments were done at baseline and at the end of each study period. Patients were stratified according to level of weight loss prior to random assignment to the treatment condition sequence.

• The study reported on 16 patients.
• Mean patient age was 62 years.
• The sample was 75% male and 25% female.
• Patients had various tumor types.
• Most patients had an Eastern Cooperative Oncology Group performance status of 1.
• All patients had experienced at least a 5% weight loss in the past six months.

• Multisite
• Inpatient setting 
• United States

• Patients were undergoing palliative care.
• The study has clinical applicability for late effects and survivorship.

The study was a double-blind, placebo-controlled, crossover, randomized controlled trial.

• Body weight
• Appetite scored on a 100 mm visual analog scale
• Anderson Symptom Assessment Scale (ASAS)
• Edmonton Symptom Assessment Scale
• Functional Assessment of Chronic Illness Therapy–Fatigue Scale (FACIT-F)
• Bristol-Myers Anorexia/Cachexia Recovery Instrument
• Caloric intake

There was no treatment effect on caloric intake. Growth hormone levels were significantly greater when patients received anamorelin compared to placebo (p = 0.005). ASAS total scores improved after three days of anamorelin (p < 0.002). Among individual symptom items, patients reported improved appetite (2.67 points with anamorelin and 0.5 points with placebo, p = 0.011). FACIT-F scores improved after anamorelin  compared to placebo (p = 0.018).

Anamorelin was shown to have some positive effects on patients’ symptoms in this small pilot study. Further research is needed to evaluate efficacy.

The study had a small sample size, with less than 30 participants.

This study was too small to enable any conclusions about the efficacy and safety of anamorelin. Further research with a larger sample is needed.

To update the 2005 Spanish Society of Medical Oncology (SEOM) clinical guidelines for the treatment of chemotherapy-induced emesis and to continue to improve the supportive care of patients with cancer

The Clinical Guideline Working Group, on behalf of the Spanish Society of Medical Oncology (SEOM) Executive Committee, provided expert opinion based on a review of the literature covering patients with cancer receiving chemotherapy.

All patients were in active treatment. This paper has application to antiemetic drugs.

• For highly emetogenic chemotherapy, one-day regimen, the following is recommended.
  • Day 1:  5-HT₃ receptor antagonist (preferably palonosetron); 125 mg oral aprepitant; and 12 mg IV or oral dexamethasone
  • Days 2-3: 80 mg oral aprepitant per day
  • Days 2-4: 4 mg oral dexamethasone every 12 hours
• For moderately emetogenic chemotherapy, one-day regimen, the following is recommended.
  • Day 1:  5-HT₃ receptor antagonist and 8 mg IV or oral dexamethasone
  • Days 2-3: 4 mg oral dexamethasone every 12 hours
• For low-emetogenic chemotherapy, the recommendation is day 1, 12 mg IV or oral dexamethasone or, alternatively, 0.5 mg/kg IV or oral metochlopromide.
• For minimally emetogenic chemotherapy, no prophylactic antiemetics are recommended.
• For multiple-day chemotherapy, the recommendation is day 1, 5-HT₃ receptor antagonist (palonosetron) and dexamethasone.
• For delayed emesis, dexamethasone is recommended.
• For refractory emesis and rescue treatment, metoclopromide, benzodiazepines, and/or phenothiazines, butyrophenones, or olanzapine are recommended.
• For acute and delayed emesis, three recommendations are made.
  • Palonosetron, a second-generation serotonin receptor antagonist, has been shown to be at least equally effective as first-generation antagonists when controlling acute emesis and more effective than first-generation antagonists when controlling delayed emesis.
  • Aprepitant, a neurokinin 1 receptor antagonist, with serotonin receptor antagonists and steroids are recommended.
  • Combining dexamethasone with other antiemetics is more effective at controlling chemotherapy-induced nausea and vomiting (CINV) than using dexamethasone alone. 
• For anticipatory nausea and emesis, use benzodiazepines, such as lorazepam.
• The authors cautioned that the use of metoclopramide as an antiemetic is limited by the presence of serious side effects such as akathisia, extrapyramidal reactions, and dose dependency.
   

Prevention of CINV can be accomplished through pharmacologic interventions, increasing patients' quality of life. The use of 5-HT₃, along with dexamethasone and aprepitant, seems to be the most effective regimen. Although these recommendations are helpful, no insight into cost implications and little discussion of potential side effects of antiemetic treatment were provided. Additionally, the recommendations offered are purely pharmacologic and, thus, only aimed at those with prescriptive authority.

PHASE OF CARE: Active antitumor treatment

The authors provide tables summarizing the emetogenic potential of common chemotherapy agents, the National Cancer Institute's classification of emesis by intensity and severity, and an algorithm of chemotherapy-induced nausea and vomiting (CINV) prophylaxis. Recommended schedules for the administration of palonosetron and dexamethasone are also provided.

No succinct list of recommendations was provided by the authors. The definition of nausea is also inconsistent with the National Comprehensive Cancer Network's definition. The article describes the different types of CINV, describes the emetogenic potential of agents, and supports an algorithm to select appropriate interventions. The authors do not state their intention outright; however, this document appears to present treatment guidelines for the Spanish Society of Medical Oncology. This guide is written in a clear style and offers straightforward recommendations for the prevention and treatment of CINV. The recommendations are grounded in the evidence, although no explanation of how the evidence was retrieved is provided. It is not possible to tell if research is drawn from a suitable representation of sources to be deemed comprehensive. Forty-three references were cited ranging from 1993 to 2013. It is assumed that the recommendations are applicable towards adults and not pediatrics but this was not stated. Recommendations for refractory and salvage antiemetic therapy are provided, but it is unclear how consensus was reached for these recommendations.

• Limitations were not explicated by the authors.
• Explanation of article retrieval is not provided.
• Procedure for reaching recommendation is not provided.
• To what degree was a consensus reached and how members resolved issues when consensus could not be reached are examples of this report’s limitations.

CINV continues to be a serious and debilitating side effect of chemotherapy for patients with cancer. Nurses should be well informed of current recommendations and guidelines for the use of 5HT3s in the prevention and treatment of CINV.

To evaluate the use of colchicine solution in the treatment of mucositis in patients with hematologic malignancies undergoing chemotherapy

Group A (control) used a 9% sodium chloride (NaCl) and water solution. Group B used a colchicine solution of 2 mg dissolved in 500 cc of sterile water starting the first day of symptoms of oral mucositis until the fifth day of the disease (inflammatory phase). Following the fifth day, patients in group B received same as group A. The solution for both groups was prepared fresh every morning. Both groups gargled for two minutes, four times a day while being supervised by a researcher. Twice a day, patients brushed with a soft toothbrush, if possible. During the study, patients were allowed concomitant interventions for oral mucositis (OM), such as systemic antibiotics, antimycotics, antivirials, antiemetics, analgesics, and granulocyte colony-stimulating factor (G-CSF) support. Cryotherapy and other oral mouthwashes were not permitted.

• The study reported on 82 patients, with a median age of 42 years in group A and 50 years in group B.
• The sample had 37 females and 45 males.
• Patients had OM and had been diagnosed with lymphoma or acute leukemia treated with high-risk chemotherapy.

The study was conducted in an inpatient cancer center in Bogota, Columbia.

This study used a single arm, nonrandomized, sequentially enrolled, historical control group.

• Oral assessments were done once a day until resolution using the World Health Organization (WHO) Oral Toxicity Scale.
• Oral pain was evaluated twice a day using a visual analog scale (VAS).
• Tolerability of mouthwash was evaluated by the patient once daily using a VAS.
• Maximum daily body temperature was recorded until OM was resolved.
• The characteristics, severity, and duration of OM, length of inpatient hospitalization, severity of OM-related pain, days of opioid consumption, tolerability of mouthwashes, change in oral pH (using pH meter), and occurrence of infection were evaluated using the Mann-Whitney test and Fisher’s exact test.
• Statistical analyses were performed using the SPSS 12.0 Statistical package.

• Patients in the treatment group experienced significantly lower median duration of OM (6 days versus 9 days) (p = 0.028).
• Patients in the treatment group experienced significantly fewer median days to healing of mucosal lesions (4 days versus 7 days) (p = 0.047).
• No differences were found in the number of days of hospitalizations, variations in weight, voice characteristics, salivation production, mucosal pH, and frequency and volume of oral mucosal bleeding.
• Oral pain assessment was similar, and no significant differences were found in opioid consumption.
• No differences were found in tolerability of mouthwashes.
• No serious side effects were reported with colchicine mouthwash.
• No differences were found in incidence of febrile neutropenia.

Colchicine mouthwash may be helpful in reducing the severity and duration of chemotherapy-induced OM.

• The sample size was small.
• The study was not randomized or blinded.
• Patients were able to use multiple other interventions for mucositis. Use of these interventions was not reported or discussed, so one cannot tell which interventions actually had an effect.

Further studies are needed to confirm results. This was done in an inpatient setting under direct supervision; these findings may not be applicable in other situations.

To evaluate two different dose escalation approaches for the combination of oxycodone and pregabalin

Patients were randomized to receive either 20 mg per day sustained-release oxycodone and escalating doses of pregabalin starting at 50 mg per day, or to pregabalin at 50 mg per day and escalating doses of oxycodone. Patients were observed for 14 days. The primary endpoint of the study was overall analgesia, defined as pain intensity reduction by at least one-third on a numeric rating scale.

• N = 67
• MEAN AGE = 67.5 years
• AGE RANGE = 39–85 years
• MALES: 56.7%, FEMALES: 43.3%
• KEY DISEASE CHARACTERISTICS: Lung, breast, and colon cancer were most prevalent.
• OTHER KEY SAMPLE CHARACTERISTICS: 72% had baseline pain scores of 6 or lower.

• SITE: Multi-site 
• SETTING TYPE: Outpatient 
• LOCATION: Italy

• APPLICATIONS: Palliative care

• Randomized, parallel group

• Pain numeric rating scale
• Allodynia recorded as present or absent by physical exam
• Patient diary for daily recording of pain severity, use of other medications, and episodes of breakthrough pain

Analgesia as defined was achieved in the pregabalin escalation group with a mean dose of 100 mg and in the other group with a mean dose of 60 mg oxycodone. No differences were seen between groups in use of rescue medication, other analgesics, or side effects.

Strategies for managing neuropathic pain with either dose escalation of pregabalin or escalation of sustained-release oxycodone when given in combination produced similar results.

• Small sample (less than 100)
• Risk of bias (no blinding)
• Other limitations/explanation: Short duration of the study

Findings suggest that similar pain management effects can be achieved with either escalation of pregabalin or escalation of oxycodone when given in combination for neuropathic pain. These findings suggest that either approach may provide similar effects and that the approach used can be determined according to relevant patient characteristics and preferences.

To evaluate the efficacy and safety of aprepitant in combination with palonsetron and dexamethasone in patients receiving three-day cisplatin-based chemotherapy

• Patients received three-day cisplatin-based chemotherapy and had never been treated with aprepitant. 
• All patients received the same antiemetic regimen of aprepitant 125 mg orally before chemotherapy on day 1 and 80 mg orally once daily on the following two days. 
• Palonosetron was given on days 1 and 3, and dexamethasone was given on days 1, 2, and 3. 
• The study physician evaluated efficacy and safety daily for seven days.  
• Patients were evaluated over multiple cycles of chemotherapy if applicable.

• The study consisted of 41 patients receiving a total of 89 cycles of chemotherapy.
• The median age of participants was 52.8 years (range = 21-74 years).
• Twenty-four patients (59%) were male, and 17 (41%) were female.
• Diagnoses were lung (32), nasopharyngeal (3), testicular (2), esophagus (2), stomach (1), and oropharyngeal (1).
• Eight of the patients were chemotherapy-naïve; 27 patients had a history of smoking, 16 had a history of drinking, 11 had a history of motion sickness, and 12 had a history of morning sickness.

This was a single-site study conducted in Guangzhou, China.

All patients were in active treatment.

This was a prospective, nonrandomized study.

Common Terminology Criteria for Adverse Events (CTCAE) of the National Cancer Institute, version 3.0, was used to assess nausea and safety.

• Findings indicated that 17% of patients had no nausea, 54% had grade 1 nausea, and 29% had grade 2 nausea. 
• With regard to vomiting, 63% had no vomiting in the acute phase, 78% had no vomiting in the delayed phase, and 58.5% had no vomiting overall. The number of patients reporting no vomiting decreased from 85% on day 1 of chemotherapy to 65% on day 3. 
• The most common side effects were hiccups (37%), fatigue (17%), headache (15%), and constipation (12%).  No adverse events were grade 2 or more. No cumulative toxicities from multiple chemotherapy cycles were reported.

Triple antiemetic medications of aprepitant, palonosetron, and dexamethasone are safe and effective for multiple-day chemotherapy to prevent vomiting.  The antiemetic efficacy is maintained during multiple chemotherapy cycles. The regimen was not as effective in preventing nausea.

• This study had a small sample of fewer than 100 participants.
• No control group was included. 
• The study was conducted at a single institution. 
• This was a nonrandomized study. 
• Descriptions of how the variables were measured were poor. For example, no information was provided on how vomiting was monitored and recorded.

Using the combination of aprepitant, palonosetron, and dexamethasone is effective in decreasing the incidence of chemotherapy-induced nausea and vomiting (CINV) in multiple-day chemotherapy regimens with low incidence of toxicity. Control of the symptom of nausea remains problematic.