To compare the impact of tramadol to that of dihydrocodone (DHC) treatment on the quality of life (QoL) and performance status (PS) of patients with cancer pain  

Patients received treatment with either tramadol or DHC controlled-release tablets for seven days. Then drugs were switched and administered for another seven days. QoL and PS were measured at baseline, at the 7th day, and on the 14th day of therapy.

• The sample was composed of 30 patients who completed the study; 40 patients were recruited for the study.
• Mean patient age was 70.5 years.
• Of all patients in the sample, 37% were female and 63% were male.
• The majority of patients had had these cancer diagnoses: lung cancer (four patients), colon cancer (four patients), stomach cancer (three patients), and tonsil cancer (two patients).
• Patients were included if they
  • Had received a cancer diagnosis.
  • Were over the age of 18 years.
  • Were opioid-naive.
  • Had no history of drug abuse.
  • Were capable of taking the medications by mouth.
  • Could communicate normally and fill out questionnaires.
  • Were experiencing nociceptive baseline pain intensity of more than 40 on 0–100 scale during nonopioid therapy.
  • Had no renal impairment.
  • Were not pregnant or lactating.

• Single site
• Inpatient
• One inpatient palliative medicine unit
   

• Phase of care: end-of-life care
• Clinical applications: end-of-life and palliative care, late effects and survivorship

Randomized crossover trial

• Visual analog scale, or VAS (0 = no pain, 100 = the worst possible pain), to measure pain intensity at baseline (before administration of analgesics) and during tramadol and DHC treatment (days 1–14)
• European Organization for Results and Treatment of Cancer quality of life questionnaire (EORTC QLQ C-30), an instrument developed for use in international clinical trials in oncology, which includes scales measuring physical, role (work), cognitive, emotional, and social functioning and global QoL as well as symptom-measuring scales relating to fatigue, nausea and vomiting, pain, dyspnea, sleep, appetite, constipation, diarrhea, and finances.   
• Eastern Cooperative Oncology Group (ECOG) scale and Karnofsky Performance Status Score, to measure performance status. (Authors did not describe performance measurement in detail. Performance status is the dependent variable; the independent variables are drug influence, treatment time effect, and interaction of drug and treatment time.)
   

• More patients in the tramadol group (12 patients) used rescue analgesics than did patients in the DHC group (8).
• Nineteen patients preferred DHC treatment, and four patients favored tramadol therapy. Seven patients thought that both analgesics were equally effective.
• ANOVA for functional scales of EORTC QLQ-C30 showed higher scores of emotional functioning in the tramadol group and higher global QoL and better cognitive functioning in the DHC group. Authors noted a trend toward better physical functioning in the DHC group (p = 0.063 for treatment time, p = 0.09 for interaction of drug and treatment time).
• In the DHC group, regarding symptom scales pertaining to drug and treatment time interaction, results of two-way ANOVA showed less fatigue (p < 0.01), pain (p < 0.001), sleep disturbance (p < 0.005), and nausea and vomiting (p < 0.001) and better appetite (p < 0.039).

DHC treatment was associated with better global QoL, cognitive functioning, analgesia, and appetite and with less fatigue, sleep disturbances, nausea, and vomiting. Tramadol therapy was associated with better emotional functioning, less constipation, and fewer financial problems. Performance status deteriorated in both groups.

• The study had a small sample, with fewer than 100 patients.
• The study had a risk of bias due to no control group, no blinding, and no washout period before the drug switch.
• The treatment period for each analgesic (seven days for each) was very brief.

Findings suggest that the decision between tramadol and DHC should be based on each patient's status and symptoms of concern. To date, no other studies have compared tramadol to DHC in patients with cancer-elated pain. Further research would be beneficial.

PHASE OF CARE: Multiple phases of care
 
APPLICATIONS: Palliative care

Oxycodone plus naloxone (OXN) appeared to provide similar analgesic effects as oxycodone, but it also improved bowel function, defined as more frequent and complete spontaneous bowel movements and less consumption of laxatives. In addition, OXN improved the passing of urine in patients with postoperative pain while reducing OIBD, improving compliance, and enhancing quality of life. OXN may be administered to opioid-naïve patients with moderate to severe pain and to patients not responding to weak opioids. The evidence from studies of chronic nonmalignant and cancer-related pain demonstrated the role of OXN in the prevention and treatment of OIBD in patients who required opioid therapy for moderate to severe pain. An evaluation of the value of the literature and studies was not evident in this article.

OIBD is a common complication in patients receiving long-term opioid treatment. The use of OXN was demonstrated by a number of studies to be effective for the management of pain and to have a role in the prevention of OIBD in patients with moderate to severe chronic nonmalignant and cancer-related pain.

Demographic characteristics were generally well-balanced between OXN groups and placebo or oxycodone groups. However, there was a larger sample size of patients with cancer-related pain in one specific study that could have altered the results. There was a high rate of variability in the type of studies that were included, and there was no critical analysis of the literature.

OXN appears to provide similar analgesic effects as oxycodone, but it improves bowel function, defined as more frequent and complete spontaneous bowel movements and a less frequent consumption of laxatives. In addition, patients receiving OXN had improved quality of life scores with decreased OIBD complications.

To evaluate the efficacy of the Caring for the Caregiver Program (CCP) to enhance the quality of life of the caregivers of patients diagnosed with advanced cancer compared to caregivers who receive standard care

Participants were randomized to receive the intervention using CCP plus standard care or standard care from home Hospice providers. Two post-test measures were used at four and eight weeks postintervention. The CCP intervention was comprised of a one-hour, face-to-face session to develop a plan of care, a video clip, two follow-up phone calls, and an invitation to join an online social support group.

• N = 56
• MALES: 26, FEMALES: 54
• KEY DISEASE CHARACTERISTICS: Stage IV cancer prognosis of at least three months
• OTHER KEY SAMPLE CHARACTERISTICS: Receiving Hospice care; English-speaking; greater than 21 years old; caregivers spent a minimum of 20 hours a week with patient; most participants were Chinese

• SITE: Home  
• SETTING TYPE: Four home Hospice and one outpatient clinic
• LOCATION: Singapore

• PHASE OF CARE: End-of-life care (stage IV)
• APPLICATIONS: Palliative care 

Pilot-randomized, controlled trial with a two-group pretest and repeated post-test

• The Caregiver Quality of Life Index: Cancer (CQOLC)
• Social Support Questionnaire (SSQ)
• Depression Anxiety Stress Scale (DASS)
• General Closeness Scale (GCS)
• Self-Efficacy in Self-Care Scale (SESCS)
• RC scale
• Caregivers' perceived knowledge of advanced care planning and community resources (six-question Likert scale)

The CCP had a positive effect on family caregivers providing care to patients with advanced cancer.

• Small sample (< 100)
• Risk of bias (no random assignment): Per the author's discussion, random sampling method could lead to selection bias on participant characteristics
• Risk of bias(sample characteristics): Only English-speaking patients were included
• Findings not generalizable: Sample size could limit ability to generalize
• Other limitations/explanation: RC scale was not clearly identified; authors should clearly state the source and validity of this scale

Identifying at-risk caregivers and implementing a CCP intervention can improve the experience of patients with an advanced diagnosis of cancer and their caregivers. These types of interventions have the potential to decrease caregiver strain and burden by improving access to social supports and improving knowledge and self-efficacy.

To assess the efficacy of MASO65D (Xclair™) in managing radiation dermatitis (RD) during radiation therapy and the follow-up period

Patients were randomized to use of MASO65D or the control cream. The control vehicle was an emollient-based cream that was similar in color and consistency but did not contain key ingredients. Patients had to observe a washout period of seven days. Patients were also instructed to apply study cream on the irradiated area three times daily, starting on first day of irradiation and continuing until three weeks after completion of radiation therapy. Patients were examined at weekly intervals during radiation therapy and three weeks after its completion.

• The study sample was comprised of female, Caucasian patients with breast cancer.
• Mean age was 57.26 years, with a range of 33.1 to 76.9 years.
• All patients scored 100% on the Karnofsky Scale.

The study took place at the European Institute of Oncology in Milan, Italy.

The study used a randomized double-blind vehicle-controlled design.

• Skin toxicity was graded using the National Cancer Institute Common Termonology Criteria for Adverse Events for erythema, desquamation, edema, moist desquamation and ulceration.
• Differences between arms of study were analyzed using the Mann-Whitney Test.
• Itch, pain, and burning were assessed using a 0–10 cm visual analogue scale, with zero being \"none\" and 10 being \"worst severity possible.
• The Karnofsky performance score, tobacco use, breast size, breast condition, and skin pigment were recorded at baseline.

The study demonstrated a statistically significant difference between vehicle and MAS065D groups regarding the maximum severity of skin toxicity (p < 0.0001), symptoms of burning within the radiation field (p = 0.039), and desquamation (p = 0.02). In the MAS065D group, 13.5% reported mild-to-moderate desquamation, compared with 50% in the vehicle group. A higher proportion of the experimental group had no desquamation. The most significant differences between the two groups were recorded after three weeks of treatment. Both study creams were well tolerated for their cosmetic acceptability. No adverse events were observed or reported in either group of patients who completed the study.

MAS065D had a significantly better outcome with prevention and treatment of skin reactions.

• The study sample size was small.
• A higher proportion of women with fair skin was allocated to the vehicle group, which has the potential to confounded findings.
• Although five patients were withdrawn from the study, results are stated for 40 patients. It is not clear if the five cases withdrawn were eliminated from the statistical analysis.
• Researchers state that results for severity of symptoms, measured with the visal analogue scale, were analyzed with Chi-square analysis or Mann-Whitney, which are not the most appropriate for integer scale data.

The intervention consisted of relaxation and guided imagery provided to patients during hospitalization. The intervention group received training in relaxation and guided imagery for 10 minutes and was given an individualized cassette for use at home and at the hospital. The recording on the cassette consisted of instructions on head-to-toe relaxation and breathing techniques. Patients were then given descriptions of pleasing images (mountains, beach, etc.) based on information gathered from the patients prior to recording of the cassette. Patients in both groups received training regarding brachytherapy, but only study group patients received training in relaxation and guided imagery.

• The study reported on a sample of 66 patients: 32 in the intervention group and 34 in the control group.
• Patients had gynecologic and breast cancers and were undergoing brachytherapy during hospitalization.

Two hospitals in Spain

A randomized controlled trial design was used.

• Hospital Anxiety and Depression Scale (HADS)
• Cuestionario de Calidad de Vida (Spanish quality-of-life questionnaire that has been validated in a Spanish population).
• Pain Visual Analog Scale
• Measures were administered prior to, during, and after brachytherapy.

The intervention group demonstrated a statistically significant reduction in anxiety (p = 0.008) compared with the control group.

• Special training or costs included creation of the training program, cassettes, and guided imagery education.
• The small sample size limits generalizability.

To evaluate the efficacy and tolerability of sublingual fentanyl for the treatment of breakthrough pain in opioid-tolerant cancer patients

This study was conducted from July 2002 to January 2004 at five university clinics in Sweden. Patients had locally advanced or metastatic cancer and were currently

• Receiving scheduled opioids equivalent to 30–1000 mg/day of oral morphine or 25–300 mcg of transdermal fentanyl
• Experiencing at least four episodes of acute breakthrough pain over a 14-day period

Each patient received, at four pain episodes occurring between 0700 and 1600 (defined as the treatment period), a placebo dose and 100, 200, and 400 mcg doses of sublingual fentanyl. The doses were provided in a random order, according to a computer-generated randomization list. At least one day fell between each treatment period, to avoid carry-over effects. Patients were asked to rate their pain at the onset of an episode of breakthrough pain and then at 5, 10, 15, 20, and 30 minutes postingestion of the study drug. At 60 minutes, the patients were asked to make a global assessment of the treatment by using a four-point scale.

• Twenty-three patients completed the study.
• The sample was composed of male and female patients 18–90 years old.
• Ten of the 23 patients were female. Mean patient age of females was 63 years, and the age range of females was 46–80 years. Thirteen patients were male. Mean patient age of males was 65 years, and the age range of males was 40–74 years.
• Patients had locally advanced or metastatic cancer, and all 23 patients were opioid tolerant and Caucasian.

• Multisite
• Outpatient
• Five university clinics in Sweden

Randomized, multicenter double-blind, four-period crossover study

• Ungraded 100 mm visual analog scale (VAS), with 0 = no pain, 100 = worst conceivable pain
• Four-point scale (none, mild, moderate, excellent)

Twenty-three patients completed all four treatment doses. Twenty-two of the 23 patients (95%) reported that at least one dose of the sublingual fentanyl produced a clinically important decrease in pain intensity, as measured by a decrease in pain intensity of more than 20 mm on the VAS. In regard to adverse events, 13 patients reported 15 adverse events considered to be related to the study drug. The most common treatment-related adverse effects were nausea and dizziness. Increasing the doses of sublingual fenanyl did not appear to increase the number or severity of adverse events, when evaluated related to increasing doses of sublingual fentanyl.

Within 15 minutes of administration, 400 micrograms of sublingual fentanyl proved more effective than placebo at significantly improving overall pain intensity difference. This was true over the entire treatment period. In regard to reducing pain intensity, results showed that the 100 and 200 mcg doses of sublingual fentanyl were more effective than placebo.

• The study had a small sample size, with fewer than 30 patients.
• Authors did not specify whether the patients were concurrently receiving treatment for cancer.
• Authors did not provide an analysis of a dose-response relationship.
• The study did not evaluate statistical differences between the dose strengths used.

Further study is needed to determine, in regard to decreasing breakthrough pain, the efficacy of each of the doses of sublingual fentanyl.

To investigate the effects of mindfulness-based stress reduction (MBSR) on sleep parameters in women with breast cancer

Patients were randomized to the MBSR group or a usual care wait-list control group. MBSR was delivered in two-hour weekly sessions six times, including educational materials related to relaxation, meditation, healthy lifestyle, practice of meditation, yoga, body scan and walking meditation, and supportive group interaction and discussion. Patients were asked to practice meditative techniques 15–45 minutes daily. Study measures were obtained at baseline, six weeks, and 12 weeks.

• N = 79–77 (completed 12 weeks)
• MEAN AGE = 57 years (SD = 9.7 years)
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: All patients were diagnosed with breast cancer and had completed initial treatment within two weeks to two years previously. All had surgery. About half had stage 3 or 4 disease.
• OTHER KEY SAMPLE CHARACTERISTICS: 73% Caucasian; 59,5% married; 80% had at least some college or vocational education; 40% had an income of $40,000 or more; 30% were employed more than 32 hours per week

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

• PHASE OF CARE: Transition phase after active treatment

Randomized, controlled trial

• ActiGraph
• Pittsburgh Sleep Quality Index (PSQI)
• Sleep diary for 72 hours after each study assessment

From baseline to six weeks, there were no differences between the groups. From 6–12 weeks, there were improvements in the MBSR group in sleep efficiency and the number of times patients awoke as measured by actigraphy (between groups Cohen’s d = 0.33 – 0.38; p = 0.04; p < 0.01). There were no differences between groups in PSQI or sleep diary findings. Sleep efficiency, the percent of time per night in sleep, was 78.2% in the MBSR group compared to 74.6% in the control group. All sleep parameters improved in both groups. There was no correlation between how much individuals practiced and sleep outcomes.

The use of MBSR resulted in improvements in some sleep parameters.

• Small sample (< 100)
• Risk of bias (no blinding)
• Risk of bias (no appropriate attentional control condition)
• Unintended interventions or applicable interventions not described that would influence results
• Other limitations/explanation: No information was provided as to whether any patients were receiving other sleep-related interventions or medications. Compliance with actigraphy, home practice, and diary use was not clear. A 4% difference in sleep time was statistically significant and had a moderate effect size, but one might question if this is clinically relevant as well. It is not clear whether the six weekly sessions were given in the first six weeks or conducted every other week over the entire course of the study. Baseline sleep efficiency scores were 80%, suggesting there may be a ceiling effect in measure as well as a testing effect with repeated use of the PSQI.

The findings of this study suggest that MBSR as provided in this intervention might improve some sleep parameters compared to usual care control patients; however, sleep parameters did improve over time in all participants. This is a low-risk type of intervention, but it involves multiple sessions delivered in person. It is not known whether different delivery methods can be successful, what the appropriate and necessary timing should be, or what the frequency and duration of the delivered interventions should be.

To compare the prevalence and severity of symptoms and symptom clusters in patients with breast cancer who participated in a mindfulness-based stress reduction (MBSR) program to the symptoms and symptom clusters in patients who received usual care.

Women who expressed interest in participating in the study were randomly assigned to MBSR or usual care. The MBSR program lasted six weeks and included educational material, meditation practice in weekly group settings and homework, group discussion on barriers to meditation, application of mindfulness in daily life, and group support interactions. Meditation training consisted of sitting and walking meditation, body scan, and gentle Hatha yoga. Researchers obtained study measures at baseline and within two weeks of program conclusion. Hierarchical-cluster analysis was used to identify symptom clusters. Researchers compared each group's symptom clusters and individual symptoms to those of the other group.

• In total, 84 participants (100% female) were included.
• Mean patient age was 58 years (standard deviation = 9.4 years).
• Median time since diagnosis of breast cancer was 11 to 15 weeks.
   

• Single site
• Outpatient
• Florida

This was a randomized, controlled trial.

MD Anderson Symptom Inventory

Severity of symptoms declined in both groups from baseline to the end of the study. Fatigue and drowsiness declined more in the MBSR group (p = 0.05). Interference scores for mood and relationships also declined more in the MBSR group (p ≤ 0.05). Analysis of changes in symptom clusters showed no differences between groups. Clusters identified were gastrointestinal (nausea, vomiting, anorexia, shortness of breath, dry mouth, numbness), cognitive or psychological (distress, sadness, pain, remembering), and fatigue (fatigue, disturbed sleep, drowsiness). Cluster scores declined in both groups.

Findings suggested that MBSR interventions may benefit women with breast cancer who are managing fatigue or mood.

• The study had a small sample size, with less than 100 participants.    
• Baseline sample/group differences were of import.
• The study had risks of bias due to no blinding and no appropriate attentional control condition.
• The control group included significantly more black patients than did the MBSR group. Ethnic and cultural differences could impact the findings.
• The study did not state whether any patients were receiving antitumor treatment or if any patients had undergone surgery.
• The gastrointestinal cluster did not make clinical sense as a cluster. 
• Enrollment occurred by means of patient self-selection.
• Symptom severity scores at baseline were low in all patients (less than 4 on a 10-point scale).

Findings suggested that MBSR may be helpful, to some patients with breast cancer, as a means of combating fatigue and mood changes. Study limitations limited the strength of these findings.

To determine whether, compared to usual care, a mindfulness-based stress-reduction (MBSR) intervention involving breast cancer (BC) survivors is efficacious in improving psychological and physical status

Patients were randomized into one of two arms: the group receiving MBSR for BC patients (MBSR (BC)) and the group receiving usual care. Assignment to group was random and stratified by stage of cancer and treatment received; if desired, members of the usual-care group were wait-listed to receive the MBSR (BC) intervention. Assessments were completed at an initial baseline orientation and within two weeks of the end of the six-week intervention or control period. Data collectors were blinded to treatment assignment. The MBSR (BC) group received six weekly two-hour sessions led by a single trained psychologist. Class size was 4–8. Subjects received a training manual and four audiotapes to support home meditation practices. Members of the MBSR (BC) group kept a daily diary. Participants completed various activities during the six-week period. The intervention comprised three specific components:

• Educational material related to relaxation, meditation, and the mind-body connection
• Practice of meditation in group meetings and homework assignments
• Discussion, among group members, related to barriers to practicing meditation, application of mindfulness in daily situations, and use of a support group.

• Sample size was 82. Participants were enrolled during the 18-month post-treatment survivorship period.
• Mean patient age was 57.5 years (SD = 9.4 years).
• Of the participants:
  • 100% were female.
  • 70% had been diagnosed with cancer at stage 0 or I; 30%, at stage II or III; and 39% had received chemotherapy in combination with radiation therapy.
  • 30% had hypertension; 10%, diabetes mellitus.
  • 25% were taking antidepressants.

• Single site
• Outpatient
• H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida

Transition phase

Randomized controlled trial

• Concerns About Recurrence Scale
• State-Trait Anxiety Inventory
• Center for Epidemiological Studies Depression Scale
• Life Orientation Test, six items assessing positive or negative life-outcome expectations
• Perceived Stress Scale-10 item
• Medical Outcomes Study (MOS) SF-36, measuring quality of life
• MOS Social Support Survey, a 19-item measure of social support
• Two Likert-scaled items widely used in epidemiologic research to measure spirituality
• MD Anderson Symptoms Inventory, which measured self-reported symptoms

• Compared to participants receiving usual care, at six weeks participants receiving MBSR (BC) had significantly lower adjusted mean levels of
  • depression (6.3 versus 9.6, p = 0.03).
  • anxiety (28.3 versus 33.0, p = 0.03).
  • trait anxiety (30.4 versus 34.5, p = 0.004).
  • fear of recurrence (9.3 versus 11.6, p = 0.007).
  • recurrence concerns (26.7 versus 36.5, p = 0.01).
• Compared to participants receiving usual care, at six weeks participants receiving MBSR (BC) had higher
  • energy (53.5 versus 49.2, p = 0.02).
  • physical functioning (50.1 versus 47, p = 0.01).
  • physical role function (49.1 versus 42.8, p = 0.03).
• In stratified analyses, subjects more compliant with MBSR tended to experience greater improvements in measures of energy and physical functioning.
• Adjusted mean scores at six weeks—for social support, perceived stress, optimism, and spirituality—did not differ by treatment assignment.

Compared to usual care, the six-week MBSR (BC) program for BC survivors, within 18 months of treatment, resulted in significant improvements in psychological status and quality of life.

• The study had a small sample size, with fewer than 100 participants; therefore, the study was underpowered. Are outcomes sustainable?
• The study did not include long-term follow-up—especially important in this case because fear and anxiety can increase as patients get further from the treatment period.
• The study did not include an attention-only or support group as a control group.
• Only 70% of MBSR subjects were considered intervention-compliant.
• Many outcomes were self-reported using validated measures. Replicating this type of program may not be feasible. The ability to generalize study results is limited.

The symptoms this study addressed continue to be of great concern to patients with cancer. Nurses must know how to help patients with these symptoms during and after treatment. Nurses should explore alternative ways to educate patients about interventions that can improve outcomes.

To determine if a mindfulness-based stress reduction (MBSR) intervention is effective in improving psychological and physical status in breast cancer survivors

The intervention was six group sessions of an MBSR program using meditation and body scan techniques. Participants received a training manual and audiotapes to support home practice of various forms of meditation and gentle yoga. The training manual included weekly objectives, exercises, program content, and a daily diary for recording practice activities.

• The study reported on a sample of 82 female patients with breast cancer.
• In terms of age, 40% were younger than 55 years, and 27.4% were older than 65 years; the MBSR group had a significantly larger percentage of younger patients.
• All patients had undergone surgery and received either adjuvant radiation or chemotherapy. Therapy was completed within the prior 18 months.
• Of the sample, 56% were employed; 72.6% were white, non-Hispanic; 78.5% had at least some college level education; and 25% were on medications for depression.

• Single site
• Outpatient setting
• Florida

• Patients were undergoing the transition phase of care after initial treatment.
• The study has clinical applicability for late effects and survivorship.

A randomized controlled trial design was used.

• Concerns About Recurrence Scale – 30 items
• State-Trait Anxiety Inventory – 20 items
• Center for Epidemiologic Studies Depression Scale (CESDS) – 20 items
• Perceived Stress Scale – 10 items assessing how often in the past month life situations were stressful
• Life Orientation Test – 6 items to assess expectancy for positive and negative life outcomes
• Medical Outcomes Study Short Form General Health Survey
• Medical Outcomes Social Support Survey – 19 items

Seventy percent of participants were determined to be compliant with the program. Intervention participants had better mean scores for state anxiety and depression compared to the control group at six weeks (p = 0.004; p = 0.03).

The MBSR program improved psychological distress, fear of recurrence, and quality of life among patients with breast cancer who recently transitioned from active treatment. The extent of practice of MBSR activities appears to influence the overall degree of benefit derived. A large percentage of patients were able to comply with a complex MBSR intervention.

• The study had a limited follow-up period.
• The study design lacked an attentional control.

Whether benefits seen were due to the actual intervention or the supportive aspects of the group was unable to be determined. More than half of eligible patients approached for enrollment declined due to scheduling issues, travel distance, lack of interest, and other issues. This suggests that such a program is limited in application related to these types of issues.