STUDY PURPOSE: To evaluate the effectiveness and side effects of cannabinoids for chemotherapy-induced nausea and vomiting (CINV) in adults with cancer

• DATABASES USED: MEDLINE, EMBASE, LILACS, PsycINFO, and Cochrane  Collaboartion 
• KEYWORDS: Search term details are provided .
• INCLUSION CRITERIA: Randomized controlled trails comparing cannabinoid with either placebo or an antiemetic medication.

• FINAL NUMBER STUDIES INCLUDED = 23

Nine trials compared cannabis with placebo. Two trials showed no difference between groups in complete absence of nausea, three trials showed likelihood of absence of vomiting with cannabinoids compared to placebo (RR = 5.7, 95% CI [2.6, 13]), and three trials showed more chance of complete absence of nausea and vomiting with cannabinoids (RR = 2.9, 95% CI [1.8, 4.7]).  Patients tended prefer cannabis to placebo. Cannabinoids versus prochlorperazine: nine trials with 1,221 patients compared these two. No significant differences in risk of CINV were found. Patients preferred cannabis in seven trials. Few very small trials of other drug comparisons were reviewed. Overall analysis of comparison with other antiemetic drugs showed the effectiveness of cannabis; however, the quality of the evidence was low to moderate level.

Analysis showed that cannabinoids were more effective than placebo and were similar to a few antiemetics for the management of CINV.

The study quality was low overall. Comparison antiemetics in included trials were not the most current and highly effective medications.

Cannabis-based medicines may be useful adjuncts for the management of CINV. More current research comparing cannabinoid efficacy alone or as adjunctive treatment with agents such as NK1 and 5HT3 would be useful. Some of the cannabis-related research has suggested effectiveness with nausea, which has not been managed as well as vomiting with current regimens.

STUDY PURPOSE: To evaluate breast cancer–related lymphedema treatment options to provide guidance to clinicians

TYPE OF STUDY: Systematic review

• FINAL NUMBER STUDIES INCLUDED = 45 
• TOTAL PATIENTS INCLUDED IN REVIEW = 1,838: 758 for CDT, 383 for MLD and compression, and 597 for invasive procedures
• SAMPLE RANGE ACROSS STUDIES: 2–139
• KEY SAMPLE CHARACTERISTICS: All had breast cancer.

PHASE OF CARE: Late effects and survivorship

• CDT: Studies showed a consistent finding of volume reduction.  
• MLD: 12 studies reported MLD with or without compression. The role of MLD as a single intervention is limited—it may have benefit incorporated into CDT.
• Compression: Seven studies showed that compression was associated with consistent volume reduction. Kinesio taping was included with bandaging and intermittent pneumatic compression.
• Invasive treatments: There were few studies of liposuction. Surgical interventions such as lymphatic bypass and node transplantation were associated with complications.

CDT is the most studied and consistently beneficial intervention.

• Limited search
• Limited number of studies included
• No quality evaluation
• Mostly low quality/high risk of bias studies
• Low sample sizes
• Very limited number of studies and only one database used

This review adds to the body of evidence showing that the use of compression bandaging and CDT are shown to be effective for managing breast cancer–related lymphedema. Nurses can recommend these interventions. Additional research is needed in the area of invasive interventions.

To determine the efficacy of relaxation and imagery for control of depression and anxiety

Patients were assigned to one of four treatment conditions:

• progressive muscle relaxation (PMR) training
• guided imagery training
• both PMR and guided imagery training
• control group

 A trained nurse taught patients the techniques in their homes, left a tape recorder and cassette, and asked subjects to practice the technique(s) twice daily. The nurse visited twice weekly to repeat the sessions.

In the control group, the nurse spent an equal amount of time with subjects, discussing general health and treatment concerns.

Investigators conducted pretesting. Post-testing occurred, for all subjects, three weeks after the initial session.

The sample was composed of 26 men and 30 women. All participants had advanced cancer and were receiving palliative care.

• Home
• Sydney, New South Wales, Australia

• Hospital Anxiety and Depression Scale (HADS), to measure anxiety and depression
• Functional Living Index-Cancer (FLIC), to measure quality of life

All three treatment groups showed significant reduction in depression, compared to the control group. No one treatment proved to be significantly superior, and none of the three treatments produced a significant reduction in anxiety.

• The study had a small sample size, with fewer than 56 participants.
• Authors did not provide a clear description of the PMR and guided imagery techniques, so replication would be difficult.
• The study occurred in one site, with one nurse conducting the interventions.
• Post-testing at three weeks showed a short-term benefit; long-term benefits were not addressed.

The intervention involved progressive muscle relaxation (PMR) and guided imagery (GI). Patients were visited by a community RN who was trained in the use of relaxation and imaging technique. Tape recorders with cassettes were used to teach PMR and GI, with instructions provided by a clinical psychologist guiding the techniques.

Patients were randomized to one of four treatment groups:

1. PMR training
2. GI training
3. Both PMR and GI training
4. Control group (pre/post-test)

• The study reported on a sample of 56 patients with advanced cancer who were experiencing anxiety and depression.
• All patients were receiving palliative care in their own homes, and all were on pain medication.

• Community nursing setting
• Sydney, Australia

A randomized controlled trial design was used.

• Hospital Anxiety and Depression Scale (HADS): Used to measure anxiety and depression
• Functional Living Index–Cancer Scale: Used to measure quality of life (QOL)

• None of the three treatments produced a significant reduction in anxiety (failed to reach significance [p = 0.057]).
• All three treatments produced a significant reduction in depression.
• All three treatments had improved QOL as measured by the index.

The study had a small sample size.

To determine the effect of the dose of platelets (high, medium, or low) on bleeding with secondary aims to determine the effect of this dose upon grade of bleeding, number of platelets transfused, and number of transfusions

Hospitalized patients were randomly assigned by a computer at a 1:1:1 ratio to receive prophylactic platelet transfusion at either a low dose, a medium dose, or a high dose (1.1 × 1011, 2.2 × 1011, or 4.4 × 1011 platelets per square meter of body-surface area) when morning platelet counts were 10,000 per cubic millimeter or lower for five days or more. Site staff was not told the patients' specific assigned dose; however, complete blindness was prevented because of differences in transfusion volume. A blood transfusion service provided the assigned dose within the allowable range of ± 25% for this study. Treating physicians could change the trigger threshold for a patient if clinically indicated. The patient would return to the study protocol trigger as soon as possible. Site-specific guidelines were used to determine red cell infusions. Patients were assessed daily for 30 days after the first infusion, at a 10-day period without a platelet transfusion, at discharge, at death, or at withdrawal from the study.

N = 1272

MEDIAN AGE: 47 years (low-dose), 50 years (medium-dose), 51 years (high-dose)

MALES: 60.4%, FEMALES: 39.6%

• SITE: Multi-site 
• SETTING TYPE: Inpatient  
• LOCATION: All around the country

• PHASE OF CARE: Active antitumor treatment

Randomized, controlled trial

• World Health Organization (WHO) criteria
• Physical examinations
• Interviews with patients
• Chart reviews for bleeding events
• Platelet counts, hematocrit values, and hemoglobin values  

There was no significant difference between the percentages of patients who a received low, medium, or high dose of platelets and bleeding.

There is no significant difference in the volume of platelets given after the trigger of 10,000 for patients. Based on these results, using the lower volume of platelets would preserve the already decreased volume of available platelet products.

• Risk of bias (no blinding)

Nurses were not blinded on this study due to the fact that they were aware of the volume that was transfused; however, this would not affect the amount of volume that was delivered to the patient. Nurses are involved in the assessment of bleeding, transfusion, and monitoring of laboratory values.

PURPOSE: To synthesize evidence regarding effects of eHealth in patients with cancer and informal caregivers from systematic reviews

• FINAL NUMBER STUDIES INCLUDED = 10
• TOTAL PATIENTS INCLUDED IN REVIEW = Not reported
• SAMPLE RANGE ACROSS STUDIES: Not reported
• KEY SAMPLE CHARACTERISTICS: Varied tumor types; mostly breast, prostate, and head and neck cancers

Evidence was found for positive effects of eHealth on knowledge and perceived support. The findings regarding effects on decision-making were inconsistent. Interventions had some positive effects on patient involvement in healthcare. The findings regarding the effects of Internet support groups on anxiety and depression were mixed. Most interventions were Internet-based and had multiple components of education, support, chat groups, and communications with providers. One study used smart phone applications.

EHealth applications have been shown to have a positive effect on knowledge. Its effects on other aspects of the patient experience are inconsistent.

All but one study were of moderate quality. Studies of low quality were excluded. Types of programs and components varied greatly, making the synthesis of effects for discrete interventions difficult.

eHealth applications may be a useful and practical way to provide patient and caregiver education. Its effectiveness as an intervention for psychological well-being and other outcomes was not clear given the mixed evidence. Ongoing research is needed to determine the full range of potential effects, program components that are most helpful, and needed duration of use for positive effects.

To evaluate the long-term safety, tolerability, and effectiveness of oxymorphone, extended release (ER), used to relieve cancer-related pain

Patients who had been taking oxymorphone ER in a previous study continued the dose they had been taking. Patients who had been taking a comparator opioid switched to an equianalgesic dose of oxymorphone ER. All patients underwent individualized dose titration to optimize effectiveness and tolerability of the opioid.

• The sample was composed of 26 patients.
• Mean patient age was 57 years.
• Of all patients, 51.2% were females and 48.8% were males. All patients had cancer pain.

Multisite

Post-hoc analysis of two open-label extension studies, each at least one year long

• Visual analog scale (VAS), 100 mm, to measure pain
• Brief Pain Inventory-Short Form (BPI-SF)
• Global assessment of study medication (1 = poor, 5 = excellent)

Of the 80 patients who entered the extension trial, 26 completed all 52 weeks. Seven patients discontinued the trial because of loss of medication effectiveness; 20 discontinued because of adverse events, most of which were unrelated to the study drug. Authors observed no significant increase in average pain intensity. The most common adverse events were concomitant disease progression (which 28.8% of patients experienced, n = 23), nausea (22.5%, n = 18), dyspnea (16.3%, n = 13), fatigue (16.3%, n = 13), and edema of the lower limb (15%, n = 12).

Patients appear to tolerate oxymorphone ER well. Oxymorphone ER provided stable long-term pain control, making it a potential alternative in the management of long-term pain.

• The study had a small sample, with fewer than 30 patients.
• The pooled extension trials had different designs and assessed effectiveness using different outcome measures and assessment intervals. The trials lacked diary data to confirm exposure to oxymorphone ER.

In this study oxymorphone ER was a well-tolerated opioid that provided long-term control of cancer-related pain. In appropriate contexts, clinicians may want to consider oxymorphone ER an alternative to standard medication.

To determine the safety and efficacy of subcutaneous (SC) methylnaltrexone in opioid-induced constipation (OIC).

Double-Blind Phase

Patients were randomized to a single dose of study drug or placebo administered SC.  Groups were 0.15 mg/kg, 0.3 mg/kg, or placebo. Patients were randomly assigned in a 1:1:1 ratio to each study group. Baseline laxative regimens could be continued. Rescue laxatives (laxatives administered on an as needed [PRN] basis) were allowed, except within four hours before or after dose administration.

Open-Label Phase

This phase was 28 days with 1 dose per 24 hours PRN. The initial dose of 0.15 mg/kg could be decreased to 0.075 mg/kg or increased to 0.3 mg/kg, based on response.

Protocol Extension

Patients completing the open-label phase could enter a three-month extension. The initial dose was the same as in the open-label phase, with dosing adjusted to 0.075 mg/kg, 0.15 mg/kg, or 0.3 mg/kg by investigator discretion.

• Of the 154 patients initially randomized, the median age was 66 years, 81.2% had a cancer diagnosis, more than 65% had World Health Organization (WHO) performance status of 3 or 4, and 95% had baseline laxative use.
• Patients were included in the study if they had advanced illness with a life expectancy of one to six months, were on a stable opioid regimen at least three days prior to study entry, had no significant laxation 48 hours prior, and had stable vital signs.
• Patients were excluded if they had previously used methylnaltrexone, naltrexone, or naloxone; process suggestive of gastrointestinal obstruction; or nonopioid constipation, diverticular disease, fecal impaction, acute abdomen, or peritoneal catheter.

Double-Blind Phase

• The age range was 21 to 100 years, with similar median ages across all groups.
• The sample comprised 54.5% men and 45.5% women, with a similar distribution across groups.
• Sixty-seven percent had a WHO performance status of 3 or higher.
• Oral morphine equivalents were 207 mg/day in the 0.15-mg/kg group, 188 mg/day in the 0.3 mg/kg group, and 150 mg/day in the placebo group.
• No significant differences existed in age, constipation distress, or mean pain score across study groups.
• At baseline, 95% used laxatives, 83% used stimulants, 56% used osmotic laxatives, and 27% used stool softener.

Open-Label Phase

• Of the 147 patients who elected the open-label phase, 72 completed the phase.
• Of the remaining 75 patients, 36 withdrew and 39 died.

Extension Phase

• Twenty-seven patients elected extension.
• Nine patients completed extension.

• Patients were recruited from hospice and palliative care settings.
• 17 treatment sites

This was a double-blind, randomized, placebo-controlled, single-dose study, followed by an open-label phase, and then an open-label extension phase.

Efficacy/Primary Outcomes

• Percent of patients who defecated within four hours of dose
• Twenty-four–hour rescue-free laxation rates
• Median time to rescue-free laxation
• Global Clinical Impression of Change (GCIC) scale (seven-point rating scale from “much worse” to “much better”)
• Improvement in stool consistency (patient report, 1 = very hard to 6 = watery)
• Constipation distress (five-point scale from 1= none to 5 = very much)

Secondary Outcomes

• Pain, as measured on a 10-point scale from 0 (none) to 10 (worst possible)
• Modified Himmelsbach opioid withdrawal scale (composite summed score for seven symptoms, each scored on a four-point scale from 1 = none to 4 = severe)
• National Cancer Institute common toxicity criteria, version 2
• WHO performance status

• In the methylnaltrexone 0.15 mg/kg group, 61.7% had laxation within four hours, 64.4% reported improvement in constipation distress, and 58.7% reported improvement in GCIC.
• In the methylnaltrexone 0.3 mg/kg group, 58.2% had laxation within four hours, 63.5% had improvement in constipation distress, and 58.8% had improvement in GCIC.
• In the placebo group, 13.5% had laxation within four hours, 34% had improvement in constipation distress, and 21.6% had improvement in GCIC.
• Comparisons between each methylnaltrexone group and placebo were significant (p < 0.00001).
• In the open-label phase (n = 72), laxation within four hours was experienced by 55.8% in weeks 1 and 2, 61.7% in weeks 3 and 4, and 63.7% at more than 8 weeks.
• Nineteen patients had AEs. Three patients in the open-label phase reported serious AEs.
• A few patients experienced abdominal pain and watery stool.
• No changes were observed in pain or symptoms of opioid withdrawal four hours after dosing.
• In the open-label phase, the 0.3 mg/kg dose was associated with more abdominal pain than the 0.15 mg/kg dose.

SC methylnaltrexone is effective in the treatment of OIC and generally is well tolerated. No relationship exists between dose and laxation response, suggesting the optimal dose is 0.15 mg/kg.

• Patients who responded to SC dosing often defecated soon after drug administration, with 50% responding within 30 minutes. Average time to defecation or timing in all respondents to the medication were not described.  Timing of response may be important for planning patient care related to toileting.
• Three patients were reported as having severe AEs. When they occurred in the open-label phase of study and what percentage of cases were affected was unclear. Investigators noted patients were frail and rapid reversal of constipation in such cases can be associated with AEs. Data for AEs in control and study groups were not provided.
• What impact continued laxative use had on the results was unclear. Many patients were on multiple types of laxatives, as well as the study drug.
• This study reported on patients with a short life expectancy and advanced disease; therefore, findings may not be applicable to other populations.

The study involved three phases: the screening visit, an open-label dose-titration phase, and a double-blind treatment phase. Titration was based on each patient's previous opioid dose. The dose of fentanyl buccal tablet (FBT) was increased stepwise from 100 mcg to 200, 400, 600, or 800 mcg until investigators identified an effective dose. If investigators could determine an effective dose for a patient, the patient entered the next phase of the study. In the double-blind treatment phase, patients were randomly assigned to 1 of 18 double- blind dose sequences (seven FBTs of the dose identified as effective and three placebos) to treat 10 episodes of breakthrough pain (BTP). Ten tablets were labeled 1–10, and patients were to take them consecutively. The treatment sequence was randomly assigned by a statistician who had used a computer to generate it. Patients continued to use their ATC regimen. If no relief occurred within 30 minutes, they continued pretrial supplemental medication.

• Study enrollment consisted of 129 patients; 87 patients entered the double-blind phase. Of these, 86% completed the study and 90% of those were evaluable for efficacy.
• Of all patients, 41% had nociceptive pain, 17% had neuropathic pain, and 42% had mixed pain.

• Multisite
• Outpatient
• Thirty treatment centers in the United States, January 2005–September 2006

Randomized double-blind, placebo-controlled design

• An 11-point (0–10) scale, to measure pain intensity (PI)
• Sum of pain intensity differences (PID) for the first 60 minutes (SPID60)
• PIDs and measure of pain relief (PR), using a five-point Likert scale (0 = none, 4 = complete), assessed from five minutes through two hours
• Patient's assessment of total pain relief
• A five-point scale (0 = poor, 4 = excellent), to measure patient's rating of global medication performance
• Proportion of breakthrough pain episodes requiring supplemental medication
• Adverse events

Investigators were able to identify an effective dose of FBT for 70% of patients. The list that follows cites the single-tablet dose of FBT that the cited percentage of patients found adequate for the treatment of two consecutive breakthrough pain episodes: 100 mcg, 8%; 200 mcg, 12%; 400 mcg, 18%; 600 mcg, 28%; 800 mcg, 34%. SPID60 favored FBT versus placebo (p < 0.0001). PIDs and PR showed significant differences versus placebo at 10 minutes (p < 0.0001). Adverse events were typical (nausea, dizziness, fatigue) and were reported in 66% of participants during the study. Ten percent had adverse events related to FBT application site. Most adverse events occurred during dose titration and were mild and transitory. Difference in SPID60 of 3 was considered clinically relevant. Sample size of 70 was associated with a power of 90%.

For opioid-tolerant patients with chronic cancer pain and breakthrough pain, FBT was efficacious and well tolerated. FBT demonstrated rapid onset (with effect within 10 minutes), and the effect of FBT was sustained.

• Most common reasons for withdrawal were adverse effects, lack of efficacy, and withdrawal of consent; 11% of patients withdrew because of adverse effects; 6%, for lack of efficacy; and 6%, for withdrawal of consent.
• The use of an open-label dose-titration phase may have increased the chance of unblinding by sensitizing patients to the effects of FBT.
• The subgroup that entered the double-blind phase had already demonstrated a favorable response to FBT. Therefore, generalizing the results to the general population is difficult. However, this process is consistent with clinical practice. This study assessed effectiveness of FBT versus placebo, not versus supplemental medications.

To determine whether patients followed by a pivot nurse/nurse coordinator would have less symptom distress and less healthcare resource utilization as evidenced by fewer unscheduled clinic visits, fewer emergency room visits, and hospitalizations than a control group

Patients were randomly assigned to a pivot nurse in addition to usual care (experimental group) or usual care only. The pivot nurse (PNO) was a baccalaureate-prepared palliative care nurse with experience and additional training in cancer symptom management. The PNO met with patients and caregivers in the ambulatory setting to review understanding of the diagnosis, expected side effects of treatment, and resources available to the patient. Patients were taught ways to identify and cope with systems and offered education and support as needed. The PNO advocated for patients in interdisciplinary rounds, developed care plans and referrals, and provided support, information, coaching, etc., via follow-up telephone calls. Usual care included symptom assessment and teaching for management, but not in a formally coordinated manner. With usual care, patients did not necessarily see the same nurse at each appointment, and telephone follow-up was usually patient initiated. The study was conducted over a six-month period. Data were collected at each clinic visit, about every three weeks, for a maximum of eight measurements.

• The study reported on a total sample of 113 patients.
• Mean patient age in the control group was 60.5 years ± 11.1; mean patient age in the experimental group was 59.3 years ± 10.7.
• Patients were diagnosed with breast or lung cancer.
• The sample was 67%–71% female and 29%–33% male.
• Of the total sample, 67%–72% were married; 36% in the control group and 51% in the experimental group had stage III or IV cancer, and 19% in the control group and 23% in the experimental group had metastatic disease; 75%–83% were deemed as having adequate financial resources; and more than 70% in both groups had sufficient help at home.

• Outpatient setting
• Canada

Patients were undergoing the active treatment phase of care.

A randomized controlled trial design was used.

• McCorkle Symptom Distress Scale (SDS)
• Functional Assessment of Cancer Therapy Scale–General (FACT-G), version 4
• Brief Fatigue Inventory (BFI)
• Hospital records

There were no differences in SDS scores over time between groups. Over time, patients in the lung cancer groups had more distress than patients with breast cancer (p = 0.023). There were no significant differences between groups for BFI findings. Patients with lung cancer reported more fatigue (p = 0.002). There were no differences between groups in FACT scores. Significantly lower quality-of-life score were reported by patients with lung cancer (p = 0.0024). There were no differences between groups in healthcare resource utilization data included in this study. Over time, patients with breast cancer were less likely to have hospitalizations shorter than 72 hours than those with lung cancer (p = 0.001).

Care provided by a PNO did not result in any difference in symptom distress or healthcare resource utilization. Patients with lung cancer had higher symptom distress, had more fatigue, and used more healthcare resources, which is in concert with differences in the disease trajectories between lung and breast cancer.

A higher proportion of patients in the intervention group had presence of metastases, and a slightly higher proportion had disease recurrence. It was not stated whether these differences were statistically significant, and these differences could have influenced results in terms of symptoms and resource usage needs. No information was provided in terms of any other chronic healthcare conditions that may have also influenced the results. Authors reported overall SDS results but did not identify actual symptoms experienced or differences at that level between groups. Clinically, different symptoms can be expected to yield different degrees of distress and needs for medical intervention and associated healthcare use. The authors reported a final sample of 113 and results in these, but provided baseline characteristics in 190 patients. One cannot evaluate actual final differences between groups in these characteristics. No power analysis was provided in order to determine if the sample size had sufficient power to detect differences. The study assumes that all practitioners in a given role should be expected to achieve standard results, while this may not be the case. The PNO in this study was not an advanced practice nurse, with associated advanced education. Nurses in the usual care group were highly experienced, and more than 75% were oncology certified. This factor may have caused there to be no substantial clinical difference in the actual nursing care provided for symptom management. The study only lasted six months—effect of better care coordination and symptom management may be more effective over a longer term. No information was provided regarding the time since diagnosis or the phase of care for patients studied, factors that could be expected to influence these aspects of care and patient needs.

This study did not provide any supportive findings for the role of a PNO as implemented in the study. Further research in this area needs to provide the ability to directly contrast this type of intervention with the nursing care provided in usual care. Research in the impact of various roles such as this, navigators, clinical nurse specialists, etc., need to provide better structure, consistency, and definition of these responsibilities and patient interactions. Inclusion of findings related to patient satisfaction with care in this type of research may be helpful.