To investigate the treatment of breast cancer–related lymphedema using massage-based manual lymphatic drainage (MLD) and bandaging and compression versus control using only compression garments

Women previously treated for breast cancer with a minimum 10% difference in volume between arms were randomly assigned to two groups. The control received only compression garments while the experimental group received MLD therapy and compression garments, and assessed for reduction in arm volume.

• N = 95  
• AGE = 59–61
• MALES: 0        
• FEMALES: 95%
• KEY DISEASE CHARACTERISTICS: Patients completed all primary and adjuvant therapy. Breast cancer–related lymphedema, treatment for breast cancer, increase in arm volume of 10% in affected arm
• OTHER KEY SAMPLE CHARACTERISTICS: Exclusions: Ongoing active cancer history of contralateral breast cancer, prior complete decongestive therapy (CDT), contraindication factors such as infection, thrombosis

• SITE:  Multi-site  
• SETTING TYPE: Outpatient  
• LOCATION: Six Canadian regional cancer centers

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

• Randomized trial 

• Circumferential limb volume 
• Quality of lIfe SF-36 
• Arm function
• DASH

CDT with MLD appears to be more beneficial to patients with lymphedema for more than one year (experimental group), showing increased volume loss, compared to control of garments only. The reduction in excess arm volume for patients in the experimental group was 29% and 22.6% for the control group (p = .34).

No significant difference in group with lymphedema less than one year, suggesting this group may respond to less intensive treatment.  More research is needed.

• Small sample (< 100)
• Baseline sample/group differences of import
• Other limitations/explanation:  Eight patients dropped out, seven from control group may have reduced the study power; use of circumferential limb volume results in some large variability.

Lymphedema identified within the first year may require less intensive therapy.  It is important for nurses to question patients with breast cancer about their affected extremity, and refer to a professional with specialized training in lymphedema management regarding risk reduction.

• FINAL NUMBER STUDIES INCLUDED = 6
• TOTAL PATIENTS INCLUDED IN REVIEW = 550 (prevention intervention); 169 (amelioration intervention)
• KEY SAMPLE CHARACTERISTICS: In both intervention groups, adults aged ≥ 18 years, received radiotherapy for the treatment of brain metastasis, primary or secondary brain tumors, or prophylaxis for other cancer. For amelioration, intervention group documented cognitive impairment in at least one cognitive domain at baseline. At least 80% of the sample had to receive radiotherapy, and radiotherapy may have been provided during childhood, but the cognitive intervention performed in adulthood.

PHASE OF CARE: Multiple phases of care

Three cognitive interventions aimed at preventing cognitive decline during radiation therapy were reported. Two were pharmacologic. One tested memantine versus a placebo and found significant improvement in overall cognitive function, and one tested methylphenidate versus a placebo but failed to detect any significant differences between groups. The third study was nonpharmacologic and investigated the use of a rehabilitation program to prevent cognitive decline but did not statistically compare differences between groups. Three cognitive interventions aimed at ameliorating cognitive decline were reported. All three were pharmacologic studies. Two studies compared methylphenidate versus modafinil and one study examined donepezil versus a placebo. Both methylphenidate and modafinil interventions resulted in improved cognitive function. Combination therapy resulted in greater adverse events. Donepezil was found to improve the domain of memory after radiotherapy.

The authors reported that there was evidence for the use of memantine for preventing cognitive decline in patients receiving radiotherapy for brain metastasis. Likewise, there was supporting evidence for the use of donepezil in improving memory after radiotherapy for primary or metastatic brain tumors. There was limited evidence for cognitive behavioral or training interventions in preventing cognitive decline.

• Small sample sizes of less than 30 subjects
• High risk of bias, particularly for nonpharmacologic interventions
• Large number of patient withdrawals

Patients who receive cranial radiation therapy for primary brain tumors or metastatic lesions are at risk for declining cognitive function. The use of memantine during radiation therapy may aid in preventing cognitive decline. Those who develop cognitive decline after the completion of radiation therapy, even years afterwards, may benefit from donepezil administration. Additional exploration of interventions that may prevent or ameliorate cognitive decline related to cranial radiation therapy is warranted.

To assess appetite response to thalidomide in cancer-associated anorexia

Patients with advanced cancer were given 50 mg of thalidomide at bedtime for two weeks. Those who responded to treatment were kept on the same dose for a total of six weeks. Those who did not respond to the 50 mg dose and were not experiencing dose-limiting toxicity were given 100 mg at night for two more weeks. If there was no response at 100 mg after two weeks and the patient was not having dose-limiting toxicity, the dose was escalated to 200 mg at bedtime.

• The study reported on a sample of 33 patients.  
• Median patient age was 69 years, with a range of 43–87 years.
• The sample was 51% male and 49% female.
• Patients had advanced, active cancer.

• Single site
• Outpatient setting
• United States

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

A prospective, observational study design was used.

• Medical history
• Neurologic exam
• Appetite, strength, pain, insomnia, night sweats, and nausea measured by 0–10 numerical rating scale (NRS)
• Appetite, tiredness, early satiety, quality of life, and toxicities (muscle cramps, pain, confusion, constipation, dizziness, drowsiness, dry mouth, headache, loss of interest in sex, nervousness, stomach pain, dry skin or pruritius, and limb swelling) measured by categorical scale (patient-perceived severity by a categorical scale [CAT])
• Eastern Cooperative Oncology Group–PS (performance score)
• Weight
• C-reactive protein (CRP)
• Lean body mass by Bioelectric Impedance (BIA)

Thirty-three patients completed at least 14 days of therapy. Sixty-four percent of patients who had completed at least two weeks of thalidomide had statistically significant appetite improvement by both the NRS and CAT (p < 0.001). Other symptoms with statistically significant improved scores included pain (< 0.05), insomnia (night sleep) (< 0.01), and early satiety (< 0.05).

Thalidomide significantly improved appetite, insomnia, pain, and early satiety from baseline in patients with advanced cancer.

• The study count is not clear as to how long patients were on which dose of thalidomide. Thirty-three patients received 50 mg for 14 days. At that time, 17 had improved appetite and 9 of the 16 nonresponders were titrated up to 100 mg. At this point it is not clear what happened with the other seven patients, but the study goes on to say that seven withdrew after two weeks, suggesting that the seven who dropped out received the 100 mg dose, which the manuscript does not corroborate. Although the methods stated that patients were titrated up to 200 mg, the results do not mention this.  
• The study states that side effects were \"negligible,\" yet at least 5 of 33 patients dropped out of the study due to side effects.  
• There was no control group for this study. Some of the lack of response to the study drug could have been due to disease progression or performance status deterioration. A larger study with a control group may have provided comparison data to assess this point.
• Adherence to medication administration was not measured.

Thalidomide may provide benefit for appetite stimulation as well as some other symptoms of advanced disease; however, the drug is not without side effects that may interfere with quality of life. This was a small study, partially funded by a pharmaceutical company, so the results should be interpreted with caution. Patients with advanced cancers on thalidomide should be educated about and assessed frequently for toxicities that may erode what little quality of life they have. Nurses must advocate for their patients who are experiencing unacceptable toxicities.

Patients were randomized to one of three study arms: 36 in the recombinant human leukemia inhibitory factor (rhu LIF) 2 mcg/kg group, 39 in the rhu LIF 4 mcg/kg group, or 42 in a placebo group. The study drug or placebo was administered one day prior to chemotherapy by subcutaneous injection after premedication with acetaminophen 1 g orally. The patient was then observed for two hours. The second injection was administered the following day, two hours prior to chemotherapy. The study drug or placebo was continued by daily subcutaneous injections for a total of seven consecutive doses per treatment cycle (every 21 days for 4–6 cycles).

• The total sample consisted of 117 patients diagnosed with solid tumor requiring chemotherapy of at least four cycles of carboplatin/paclitaxel.
• Exclusion criteria included having a clinically significant medical condition, having more than one prior course of chemotherapy for metastatic disease, having any prior neurotoxic chemotherapy requiring dose modification due to neuropathy, having brain metastasis, a history of alcoholism, or having preexisting neuropathy

The study had a phase II, double-blind, placebo-controlled clinical trial design.

• Neurologic assessments were performed prior to study drug administration following the fourth cycle of chemotherapy and last cycle of chemotherapy and at 3 months post chemotherapy.
• CPNE assessment consisted of peripheral nerve electrophysiology testing (antidromic maximal conduction velocity), amplitudes of three sensory nerves (sural, median and ulnar) and one motor nerve (peroneal) and vibration threshold of the non-dominant great toe.
• Neurologic signs were measured using the Einstein Neurologic Examination, assessed as 0 (absence of deficit) to 3 (severe, bilateral deficit involving proximal sites). A total score is obtained ranging from 0–15.
• Change in symptoms was measured using a subset of questions from the CIPNS-32. The severity of each symptom (0–4) and the extent it interfered with normal function (0–5) were rated on a scale, with a total possible score ranging from 0–100.

rhu LIF was fairly well tolerated, with five patients reporting adverse events that included lightheadedness, rigors or chills, myocardial ischemia, and hypotension. CPNE scores showed small but consistent decrement between baseline and cycle 4 of chemotherapy. Vibration threshold was also altered by chemotherapy. Intent-to-treat analysis showed no significant differences in CPNE scores between the three groups. 

No evidence showed that rhu LIF prevented, delayed, or diminished CIPN.

While sample size was calculated to be adequate by a power analysis, the goal of 40 patients per group was not achieved, and the original calculation may not have been accurate to achieve statistical significance.

Since the measures were sensitive enough to detect CIPN, no further plans to develop rhu LIF as an agent to treat or prevent CIPN were proposed.

Keywords searched were cannabinoids, nabilone, nausea, pain, tetrahydrocannabinol, and vomiting.

This was a review of published English literature, including reviews, meta-analysis, and treatment trials from 1975–1997 on using cannabinoids to control or prevent chemotherapy-induced nausea and vomiting (CINV), with very few trials found after 1997. From this review, 30 randomized control trials were found that looked at cannabinoids to control or prevent CINV. Overall, the trials received low scores for adequacy of randomization, blinding design, and description of withdrawal. Three cannabinoids were studied: nabilone (16), dronabinol (13), and levonantradol (1). The medications were compared to prochloperazine (12), placebo (10), metochlorpramide (4), chlorpromazine (2), domperidone (2), alizapride (1), thiethylperazine (1), and haloperidol (1). Twelve studies involved various scoring systems. No clear separation existed between acute and delayed CINV.

The trials included 1,760 patients, with 394 excluded.

• Nabilone was found to be superior to placebo, domperidone, and prochlorperazine but not metoclorpramide.
• Cannabinoids did not add to the benefits of 5-HT₃ receptor antagonists.
• Side effects were greater for nabilone than prochloperazine in these studies, but patients preferred nabilone to prochloperazine.

• The major limitation of these studies was the grading of response and the inability to differentiate between acute and delayed CINV.
• The adequacy of randomization, blinding design, and description of withdrawal were insufficient.
• The time period for the review was limited to 1975–1997. From 1997–present, many changes in managing CINV have occurred.
• The databases of the search were not indicated.

Cannabinoids, like nabilone, may have a role in reducing delayed or refractory CINV, but more evidence is needed.

The Science Committee of the Association for Palliative Medicine of Great Britain and Ireland convened a task group to produce up-to-date, evidence-based clinical guidelines regarding the management of cancer-related breakthrough pain in adult patients. Literature review provided limited evidence, only case series and expert opinion, and the task group could make no recommendations about any particular intervention.

Face-to-face group meetings initiated the review process and determined the scope of work. A draft set of recommendations was circulated to group members, and all members were in agreement regarding content. Authors did not describe the process of evidence grading or how the recommendations were drafted. A final meeting was held to finalize results. The MEDLINE keywords searched to retrieve reviews were breakthrough pain, incident pain, and episodic pain. The search was for the years 1950–2007. In addition to the MEDLINE search, investigators manually searched reference lists of retrieved papers and major texts. Authors did not specify inclusion or exclusion criteria. Evidence was graded according to the Scottish Intercollegiate Guidelines Network (SIGN) system.

• Authors noted these points regarding breakthrough pain:
  • The definition the authors adopted of the term breakthrough pain was “a transient exacerbation of pain that occurs either spontaneously, or in relation to a specific predictable or unpredictable trigger, despite relatively stable and adequately controlled background pain.” (p. 332)
  • Authors noted that no definition of breakthrough pain is common to much of the work in this area.
  • Breakthrough pain was categorized as either idiopathic (unrelated to a precipitant) and unpredictable or incident (related to an identifiable precipitant).
• Authors noted that the guidelines they provided were based on consensus, not levels of evidence.
• Authors provided a simple algorithm of a dose-titration scheme for opioid rescue medications.

The guidelines make the recommendations that follow.

• Patients with pain should be assessed for the presence of breakthrough pain. Differentiating between uncontrolled background pain and controlled background pain with breakthrough pain is important.
• Patients with breakthrough pain should be assessed specifically for breakthrough pain. Authors note that no assessment tool for breakthrough pain exists, so guidelines recommend assessing breakthrough pain by using standard means of pain assessment.
• Management of breakthrough pain should be individualized—that is, reflect patient-related factors and preferences. In many cases, however, options are limited by availability and affordability of interventions. Guidelines recommend balancing the cost of the intervention with the cost of uncontrolled breakthrough pain.
• Those who determine treatment should consider the underlying cause of pain. Evidence supports the efficacy of cancer treatment in the management of background pain, but no evidence relates to breakthrough pain specifically.
• Caregivers should consider the benefits of avoiding precipitating factors versus treatment of precipitating factors. For example, practical support with activities of daily living and simple adaptation of surroundings could mitigate movement-related pain.
• Those who determine treatment should consider modifying the background analgesic regimen. Modification strategies could include
  • Titration of opioid analgesics.
  • Switching opioid analgesics.
  • Addition of adjuvant analgesics (such as antieleptics for neuropathic pain or antispasmodics for visceral pain).
  • Addition of other adjuvant drugs for relief from the side effects of pain medication.
  • Other strategies (e.g., use of nonanalgesic drugs, anti-inflammatories).
• Opioids are the rescue medication of choice in the management of breakthrough pain. Decisions regarding specific preparations and routes should be based on pain characteristics and the patient’s previous response to opioids. Oral opioids may have a role in breakthrough pain but are not typically the optimal approach.
• Individual titration should determine the dose of opioid rescue medication. Guidelines suggest that the traditional approach—that the dose of opioid rescue medication should be a fixed proportion of the background medication—is not the most effective.
• Nonpharmacologic methods may be useful in the management of breakthrough pain episodes. Guidelines mention rubbing or massage, application of heat or cold, distraction techniques, and relaxation techniques, though authors note that little evidence shows that these methods are effective.
• Nonopioid analgesics may be useful in the management of breakthrough pain episodes. Interventions that have been used include nonsteroidal anti-inflammatory drugs, ketamine, midazolam, and nitrous oxide.
• Intervention techniques may be useful in the management of breakthrough pain. Interventions include neuraxial drug infusion, neural blockade, neuromodulation (e.g., transcutaneous electrical nerve stimulation, or TENS), and interventional radiologic techniques.
• Breakthrough pain, specifically, should be reassessed.
• Patients with pain that is difficult to manage should be referred in a timely manner to a pain specialist or palliative care specialist.

Three members of the task force consult for pharmaceutical companies.

Breakthrough pain is heterogeneous and highly individual; clinicians and caregivers should approach it with these facts in mind. Little evidence guides the management of breakthrough pain. Current teaching is not in concert with recommendations related to the usual practice of prescribing a fixed proportional dose of background opioids as rescue medications. Guidelines point to the need to consider breakthrough pain as an issue separate from background pain. The use of rescue medications is only one aspect of managing breakthrough pain; clinicians should remember other approaches, such as treatment of the underlying causes of the pain. The field of oncology needs research aimed specifically at the management of breakthrough pain.

The objective of the study was to determine if indwelling pleural catheters (IPCs) are more effective than talc slurry pleurodesis via chest tube for relief of dyspnea.

Patients with symptomatic malignant pleural effusion requiring pleurodesis were randomized to either IPC or talc pleurodesis. IPCs were inserted, initial large-volume drainage was performed, and caregivers were trained in IPC management. Drainage was advised to be done three times weekly. The IPC was removed if significant drainage stopped for at least four weeks, with no evidence of fluid reaccumulation. Patients in the talc group were hospitalized and had percutaneous chest tube insertion and talc slurry pleurodesis with 4 g sterile high-grade talc, following published treatment guidelines. Patients were followed up for 12 months after randomization. Dyspnea measurement was recorded daily for 42 days and then at 10, 14, 18, 22, and 26 weeks, and at 9 and 12 months.

• The sampe was comprised of 96 patients.
• The mean patient age was 76 years (SD = 11.5 years).
• Of the 96 patients, 43.5% were males and 56.5% were females.
• Various cancer types were included in the sample, but breast and lung were most frequent.
• The average size of effusion on radiography as a hemothorax was 51% in the IPC group and 49% in the talc group.
   

The study was conducted in multiple settings in the United Kingdom.

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

The study was an unblinded, randomized controlled trial.

• 100 mm Visual Analogue Scale (VAS) for dyspnea
• EORTC - Quality of Life Questionnaire
• Complication recording
• Use of healthcare resources
   

• No significant difference in dyspnea was observed between groups.
• Dyspnea declined in both groups, with a mean decrease of 37.0 mm with IPC and 30.2 mm with talc. 
• At 6 months, a clinically significant decrease was seen in dyspnea in the IPC group compared to the talc group ( - 14.0 mm, p = .01). 
• Over 12 months, the IPC group spent an average of one day in the hospital for drainage or complications, compared to an average of 4.5 days in the talc group (p < .001).
• Global quality of life improved in both groups, with no significant difference between groups at any time point.
• In the IPC group, 40% experienced any adverse event, compared to 13% in the talc group (p = .002). 
• No difference in serious adverse events was observed between groups. 
• Pleural infections occurring with IPCs were asymptomatic and treated with oral antibiotics, and no IPC had to be removed for infection.

• Both talc pleurodesis and IPC were effective in reducing dyspnea in patients with malignant pleural effusion. 
• No significant difference in effectiveness was seen between the two approaches.
• IPCs reduce hospitalization time but are associated with more adverse events.

Because it was unblinded, the study had the risk of bias.

• Both approaches demonstrated effectiveness for reducing dyspnea in this group of patients. 
• Patient selection for IPC use needs to include consideration of caregiving needs and capabilities to manage the catheter, given the tendency for higher adverse events with its use.

To compare the efficacy, tolerability, and patient acceptability of fentanyl-pectin nasal spray (FPNS) with that of immediate-release morphine sulfate (IRMS)

This study consisted of four phases: a screening phase (maximum 10 days), an open dose-titration phase (maximum 14 days), a treatment phase (minimum three days, maximum 21 days), and an end-of-treatment phase (1–14 days after the last dose). The open dose-titration phase was used to identify the FPNS dose, 100–800 mcg/episode of breakthrough pain, that was effective. Patients who achieved an effective dose in titration were eligible for the treatment phase. Five of a patient's breakthrough episodes were treated with FPNS and oral placebo and five episodes were treated with IRMS and placebo nasal spray. Scores rating pain relief were recorded at 5, 10, 15, 30, 45, and 60 minutes after treatment.

• Seventy-nine patients completed the study.
• Mean patient age was 55.9 years (SD = 12.3 years).
• Authors did not specify the percentages of females and males in the sample.
• All patients had a cancer diagnosis, but authors did not provide details about cancer type, extent, or treatment.
• All patients were on a fixed schedule of opioids: a dose equal to or greater than 60 mg/day morphine.

• Multisite
• Outpatient
• 35 centers in Europe and India

Randomized, double-blind/double-dummy (DB/DD) crossover study

• E-diary that prompted the patient at specific time points to rate pain on an 11-point scale (0 = no pain, 10 = worst possible pain)
• Numeric scale to measure pain relief
• Self-report, of relief speed and reliability of the nasal spray, by means of a four-point scale that a patient used after completing a 10-item questionnaire

• Per-episode analysis revealed that FPNS consistently provided relief from pain more rapidly than did IRMS (p < 0.05).
• Overall acceptability scores were significantly greater for FPNS than for IRMS at 30 minutes (P < 0.01).
• Only 4.7% of patients withdrew from titration because of adverse effects; no significant nasal effects were reported.
• Overall, the percentage of episodes requiring rescue medication was similar between the two groups: Of all episodes of breakthrough cancer pain, 97% treated with FPNS did not require additional rescue medication and 96.2% treated with IRMS did not require additional rescue medication.
• Overall, only eight patients (six after treatment with FPNS and two after treatment with IRMS) experienced treatment-related adverse effects that resulted in the discontinuation of the study drug.

This is a strong, well-conducted study that demonstrates that FPNS is efficacious, well accepted, and well tolerated by patients with breakthrough cancer pain.

• The study had a small sample size, with fewer than 100 patients.
• Limitations of the study include its relatively short duration and the lack of IRMS titration.

FPNS is an effective alternative for management of episodes of cancer-related breakthrough pain. Nasal spray may be a route that is particularly helpful for patients who have to take a lot of oral medication. Nurses should be aware that most studies of nasal sprays have been of relatively short duration. Nasal sprays do not seem to have adverse effects on the nasal passages, but the potential effects of long-term use are unknown.

RESOURCE TYPE: Expert opinion

PHASE OF CARE: Active antitumor treatment

• Antidiarrheals for grade 1 diarrhea, and corticosteroids if diarrhea progresses to grade 2
• Systemic corticosteroids for severe, persistent, or recurring adverse events
• Dose delay for moderate adverse events until recovery and discontinuation of treatment for severe reactions

• Expert opinion level evidence
• Provides an overall general approach to the management of adverse events rather than specific treatment algorithms

Provides general concepts for the management of immune-related adverse events

To examine the initial efficacy of a sleep therapy program developed for treating insomnia in patients with cancer.

Participants received multimodal cognitive-behavioral therapy in five weekly group therapy sessions followed by a final sixth session held four weeks later. The sessions included stimulus control therapy, relaxation training, sleep consolidation strategies, and strategies to reduce cognitive-emotional arousal. Outcomes measured included several sleep-related measures, and several European Organisation for Research and Treatment of Cancer Quality of Life Questionnare (EORTC QLQ-C30) measures, including role functioning, insomnia, and fatigue.

• The study was comprised of 14 participants, 12 of whom completed the study.
• Mean age was 54.7 years.
• Participants had mixed cancer diagnoses.
• Mean time from diagnosis was 33.6 months.

The study was conducted at outpatient clinics at a major cancer center in Ontario, Canada.
 

Patients were undergoing the long-term follow-up phase of care.

This was a repeated measure, quasiexperimental study with no control group.

• Sleep diary
• Sleep Impairment Index (SII)

Sleep improved from baseline to four weeks and to eight weeks after the intervention. Improved sleep measures included the number of awakenings, wake after sleep onset, and sleep efficiency.

• The study had a small sample size.
• The participants were relatively healthy.
• The study only used self-reported data.
• There was no placebo control group.
• The duration of effects after eight weeks was unknown.
• Space was needed to provide the intervention.