To evaluate quality of life, anxiety, depression, and provider-patient communication in patients with breast and gynecologic cancers with advanced disease stopping active treatment based on the care model used (integrated [ICM] compared to traditional [TCM])

Patients who had received anticancer treatment that was discontinued and were followed up only in the palliative care unit were recruited. Consented patients were evaluated by a treating physician using the Communication Assessment Protocol (CAP). The patients then completed the CAP. The CAP was aimed at determining the degree to which patients had been informed about the reality of their diseases. Patients were categorized for group placement for study comparisons. Those who had been evaluated at least once for palliative care were placed in the ICM model (included PC commitment team and active cancer treatment). Those with no prior consult were placed in the TCM model. Patients in both groups completed study assessments.

• N = 87
• MEDIAN AGE = 56 years (range = 24–83 years)
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: Advanced breast and gynecologic cancers with monastic disease or inoperable recurrences; patients with uncomfortable and uncontrolled symptoms were excluded from study participation
• OTHER KEY SAMPLE CHARACTERISTICS: Gynecologic diseases included cancers of the endometrium, ovary, uterine cervix, and vulva/vagina. Subjects were told that once they enrolled in the study, they would not receive additional anticancer treatment. There were no neuropsychiatric problems, major cognitive impairments, or uncomfortable symptoms impairing questionnaire completion.

• SITE: Single-site
• SETTING TYPE: Not specified
• LOCATION: Sao Paulo, Brazil

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

Prospective, descriptive, two-group comparison

• Hospital Anxiety and Depression Scale (HADS)
• European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)
• Karnofsky Performance Status
• Communication assessment protocol

KPS scores ranged from 30–90 (median = 50). Previous treatment included up to eight different lines of systemic palliative treatment (mean = 2.7). There were no group differences between the two care models. The ICM care group had higher global health (p = 0.022), emotional functioning (p = 0.034), and social functioning (p = 0.018), and it had lower insomnia scores (p = 0.027) compared to the TCM group. A smaller proportion of those in the ICM group demonstrated HADS scores at a level indicating clinically relevant anxiety (HADS ≥ 11, p = 0.018). There was no correlation with the number of consultations with the palliative care team. The ICM group experienced significantly fewer communication problems (p = 0.004). The ICM group received less chemotherapy in the last six weeks compared to the TCM (p = 0.001). There was no significant difference between groups in fatigue, anorexia, constipation, pain, or diarrhea. Multivariate analyses showed increased prognostic factors for survival in the ICM group.

Early palliative care may improve quality of life and reduce insomnia and symptoms of anxiety in patients at the end-of-life phase of care.

• Small sample (< 100)
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Other limitations/explanation: Patients with significant symptoms were excluded from the study, so the sample was biased from the beginning toward individuals with less symptom distress. This factor could be expected to bias study results.

This study sought to show that offering appropriate and timely palliative care using the ICM model can reduce symptom burden during the transition into advanced disease and death. This study provided little support because of study design flaws. There was limited research on the effects of early palliative care. Additional research is needed to test this model in the United States and focus on integration into practice.

To investigate the safety and efficacy of transdermal buprenorphine in the treatment of chronic cancer pain in children

Patients receiving other analgesics were transitioned to transdermal buprenorphine. The initial dose was 8.75–35 mcg/hour, depending on body weight. Patches were changed every three days. If needed, the dose could be titrated by means of a standard scheme. Study evaluations were done on days 4, 7, 14, 30, 44, and 60. Rescue medication, tramadol 1–2 mg/kg for breakthrough pain, was allowed as needed but not more than twice daily. School-age children self-reported study measures. Parents reported measures related to younger children.

• The sample was composed of 16 patients.
• Mean patient age was 11.06 years. Age range was 2–17 years.
• Of all patients, 56.3% were male and 43.7% were female.
• Patients had various tumor types; most were central nervous system tumors, bone sarcomas, and lymphomas. Of all patients, 75% had metastasis, 87.5% had had chemotherapy, and 75% had had surgery. Patients had not undergone previous opioid treatment and had moderate to severe pain—that is, pain measuring 6 or higher on the visual analog scale—that was not satisfactorily controlled.

• Single site
• Outpatient
• Italy

Clinical application: pediatrics

Prospective observational study

• Wong-Baker FACES Pain Rating Scale
• Four-point scale, to measure sleep quality
• Three-point scale, to measure level of play, alimentation, speech, and activity
• Scale measuring global assessment of treatment efficacy
• Use of rescue medication
• Four-point scale, to measure adverse events
• Response (response = pain intensity score reduction of at least 2 and use of rescue medication no more than twice daily)

• After two weeks, 68.75% of patients responded to transdermal buprenorphine treatment.
• Over the course of the study, pain intensity declined from 6.35 ± 0.68 at baseline to 1.38 ± 1.89 at day 60 (p < 0.001).
• Quality of sleep, alimentation, play, and speech improved over time (p < 0.001). 
• By week 4, 40% fewer patients required rescue medication.
• Overall efficacy and patient compliance were positive.
• Authors rated tolerability as good or very good in 100% of patients by the end of the study. Of all patients, 100% rated efficacy as good or excellent.
• The most common adverse effects were nausea, vomiting, and constipation.
• Mean buprenorphine dose was 32.6 ± 14.78 mcg/hour; the dose range was 0.5–1.8 mcg/kg/hour.

Transdermal buprenorphine was effective at treating chronic cancer-related pain in pediatric patients. Patients tolerated the drug well.

• The study had a small sample, with fewer than 30 patients.
• The study had risks of bias due to no control group, no blinding, and no random assignment.
• Authors did not describe means of measurement or methods well.
• Rating scales were not evaluated.
• Investigators, not patients, rated tolerability.

Findings suggest that pediatric patients can safely use transdermal buprenorphine and that it is effective at treating the pain of the specified patients. Nurses should be aware that these findings resulted from a study with a very small sample; the findings may not reflect actual frequency of adverse events. Pediatric patients should be closely monitored for adverse events. The side effects of transdermal buprenorphine in children are the effects typical of opioids; care should include a prophylactic approach to side effect management.

The objective of the systematic review was to assess the effectiveness of non-invasive interventions delivered by healthcare professionals in improving symptoms, psychological functioning, and quality of life.

Databases searched were Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, PsycINFO, AMED, British Nursing Index and Archive, and reference lists from relevant studies.

Search keywords were non-invasive interventions and lung cancer.

Randomized controlled trials and controlled clinical trials were included. The trials included involved

• Patients of any age or gender diagnosed with lung cancer
• Any stage of illness
• Any non-invasive intervention treatment or action performed by healthcare professional to enhance well-being or quality of life defined to include symptoms related to cancer.

A total of 20 references were retrieved. Two authors independently assessed all the references. Three of 15 studies included in this review were evaluated together in one category labeled “Nursing Interventions to Manage Breathlessness.” Of the three studies that focused solely on breathlessness, two studies previously were evaluated in the 2009 Putting Evidence Into Practice publication.  

The final number of studies included was 15. The breathlessness category included 165 patients with lung cancer. The sample range across studies was 22-109.

Patients had lung cancer with refractory breathlessness, the majority of which were not receiving active therapy. Patients received breathlessness rehabilitation, which focused on emotional as well as physical aspects of the symptom, or breathlessness training intervention, described as training in diaphragmatic breathing, pacing, anxiety management, and relaxation.

The three studies found that the intervention was effective in improving the sensation of breathlessness at best and also had beneficial effects on performance status, functional ability, and depression. Due to the stage of disease and limited life expectancy of those diagnosed with advanced lung cancer, rapid deterioration and attrition were seen in one of the studies.

The studies of breathlessness management indicate that nurse-led breathing programs may produce beneficial effects and should be encouraged.

To investigate the efficacy of palonosetron for prevention of chemotherapy-induced nausea and vomiting (CINV) caused by adjuvant temozolomide (TMZ) in patients affected by glioblastoma

After completion of concomitant radiotherapy plus daily TMZ (75 mg/m²) in patients with stable disease or better, 30 minutes before the beginning of the first cycle of adjuvant TMZ (150-200 mg/m² per day for five consecutive days every 4 weeks), patients received a single IV bolus of 0.25 mg palonosetron. All patients were receiving oral or parenteral dexamethasone (range 2–8 mg/day) with steady doses from at least 14 days before adjuvant TMZ initiation.      

Patient diaries were used to record any emetic episodes, nausea, or rescue medication in daily (24-hour) intervals. The daily rates of emesis and nausea were assessed using a Likert-type scale. The primary endpoint was the percentage of patients with complete response (CR), defined as no emetic episodes and no rescue medication during the overall phase (0–168 hours).

• The study reported on 33 patients with a median age of 57.6 years.
• The sample was 70% male and 30% female.
• Patients had glioblastoma (GBM) with disease control after combined radiochemotherapy; normal hematologic, renal, and hepatic function; and Karnofsky Performance Status (KPS) of 70 or higher.

This study was conducted at a single-site, outpatient setting at the Clinical Oncology Unit of Istituto Neurotraumatologico Italiano (I.N.I.) in Rome, Italy.

• Patients were undergoing the active treatment phase of care.
• The study has clinical applicability for elderly care.

This was a prospective, open phase II study.

• Patient diaries were used to record any emetic episodes, nausea, or rescue medication in daily (24 hour) intervals.  Complete response (CR), defined as no vomiting and no use of rescue medications, was measured, as well as complete control (CC), defined as no emetic episodes, no rescue medication, and no more than mild nausea.      
• A Likert-type scale was used to measure 

Complete response during the overall treatment period (0–168 hours) was observed in 30 patients (91%). Complete response in the 0–120-hour and 121–168-hour phases was observed in 30 patients (91%). Complete control was seen in 29 patients (88%), in 30 patients (91%), and in 29 patients (88%) during the 0–120-hour, 120–168-hour, and 0–168-hour phases, respectively.

The results suggested that a single dose of palonosetron before the initiation of multiple oral doses of TMZ, in patients receiving treatment with steady doses of dexamethasone, provides a high level of protection against CINV throughout the overall phase (0–168 hours). Discerning the affect of dexamethasone on nausea prevention was difficult in this study. Understanding the full impact of this regimen is challenging. A similar study conducted with ondansetron or another oral 5-HT₃ RA would be interesting. If oral antiemetics are able to achieve similar results, they may be more cost effective and convenient for patients.

• The sample size was small with fewer than 100 patients.
• Patients were given different doses of dexamethasone. Although the dose of dexamethasone was required to be stable for 14 days prior to study entry for each patient, the difference in dose may have impacted the antiemetic properties of the dexamethasone/palonsetron regimen.  
• The majority of the sample was men (70%), which may play a role in the rate of effective nausea/vomiting control. Women tend to be at higher risk for chemotherapy induced nausea. Conducting the study using a sample with a more even sex distribution would be interesting.

More antineoplastic drugs are being given orally at home. This study looked at the use of an antiemetic regimen used with an oral drug. Studies like this will become increasingly important as oral continuous-dosing drug regimens emerge.  Adequate control of nausea and vomiting is essential for oral therapies, because lack of control can lead to patient noncompliance.

DATABASES USED: MEDLINE

COMMENTS ON LITERATURE USED: Articles published from 1966–2000 related to methylphenidate use in patients with cancer or in palliative care

FINAL NUMBER STUDIES USED = 49 

The evidence in the review found that methylphenidate is useful for the treatment of depression in a variety of malignancies, with more than 80% improvement in depression and side effects in less than 20%.

To evaluate the impact of washing breast skin with soap and water during radiation therapy on the intensity of acute skin toxicity

Patients were randomized prior to receiving radiation into two groups. In group 1, skin within the treatment field was not allowed to be washed. In group 2, skin within the treatment field could be washed with Dove^® or Ivory^® soap and water. Patients were not to apply any other materials unless prescribed by a physician. Topical treatment was prescribed for 87% of non-wash patients and 80% of wash patients for a mean duration of 18.2 and 17.6 days, respectively. The topical agents prescribed were topical corticosteroids, eosin, Burow’s solution, and Biafine^®. Patients were requested not to tell physicians if they were washing the irradiated area or not. Skin toxicity was independently scored by the author and radiation oncologist.

• The study sample was comprised of 99 patients with breast cancer who received treatment in group 1 (n = 49) or and group 2 (n = 50).
• Mean patient age was 56 years in group 1, with a range of 33.2–78 years, and 58.4 years in group 2, with a range of 27.6–84.2 years.
• Sixty-nine percent of group 1 and 72% of group 2 were postmenopausal.
• Total prescribed dose was more than 40 Gy.

The study took place at an institution in Quebec, Canada.

The study used a randomized, blinded, controlled trial design.

• Acute skin toxicity was recorded according to the Radiation Therapy Oncology Group (RTOG) scale before radiation therapy, weekly during radiation therapy, and one month after end of radiation therapy.
• Subjective assessment for pain, itching, and burning was scored by visual analog scales at the same time intervals.
• Other data included type of washing, frequency of washing, radiation technique, necessity for second simulation, and interruptions of treatment.
• Analysis was performed on an intent-to-treat basis, and no patients were excluded.

In group 1, 57% had grade 2 or higher skin toxicity. In group 2, 36% had grade 2 or higher skin toxicity (p = 0.04). Mean time to maximal toxicity score achieved was not different between the groups. Maximal erythema score was not significantly different between the two groups. Incidence of moist desquamation was significantly higher in group 1 (p = 0.03). Dry desquamation (one month after treatment) was experienced by 74% of patients in group 1 compared with 56% of patients in group 2. The difference was not significant. Variables in univariate model significantly associated with acute skin toxicity included group 1, chemotherapy as part of treatment regimen, concomitant chemotherapy, presence of hot spots on dosimetry, and increased patient weight.

Allowing patients to wash irradiated skin did not result in any increased skin toxicity.

• Patients were treated with a combination of cobalt and megavoltage equipment.
• Fifteen percent of group washed during the study.
• Soap used was not consistent, as advised in group 2.
• Not clear how use of topical agents may have also affected results.

To evaluate the effectiveness of a residential rehabilitation course for patients with cancer in decreasing psychological distress

Patients who had completed cancer treatment were randomly assigned to receive either usual care or a six-day residential psychosocial course. Those in the residential group had weekly rehabilitation courses in groups of 20. Course activities included education, supportive talks, physical activity, relaxation, massage, social activities, peer discussions, and dietary instruction. At the end of the course, individuals created a personal action plan to reinforce what was learned. Data were collected at baseline and at 1, 6, and 12 months after completion of the intervention.

• The study reported on a sample of 394 patients.
• Mean patient age was 61 years (range = 39–82 years).
• The sample was 64.4% female and 32.2% male.
• Patients had diagnoses of breast, prostate, or colon cancer.
• Average time since diagnosis was 15 months (range = 2.5–28.1 months).
• Of the sample, 48% were employed, 47.5% had higher than youth education, and 72% were married or cohabiting.

• Single site
• Other setting
• Denmark

Transition phase of care after initial treatment

Randomized controlled trial

• Profile of Mood States Short Form
• EORT QLC-C30

At one-month time point, findings revealed significantly more improvement in anxiety (p = 0.03), total mood disturbance (p = 0.04), emotional role function (p = 0.02), and cognitive functioning (p = 0.0009) in the control group. At the six-month time point, a significantly improved outcome for the control group was also found for depression (p = 0.005) as well as sustained improvement in anxiety (p = 0.003), total mood disturbance (p = 0.02), emotional role function (p = 0.04), and cognitive functioning (p = 0.03).

The residential rehabilitation course studied did not have a positive effect on anxiety, depression, or cognitive functioning. In this study, the control group improved more over time than those who received the intervention.

• The study had a risk of bias due to no blinding and no appropriate attentional control condition.
• This type of residential program or intervention would require training and be expensive and impractical for many individuals. It is not clear if participants incurred any costs to participate.
• Usual care was not described.
• Measurement for cognition was one item on a subjective measure.
• There was 13% attrition at time of six-month follow-up testing.

 This study suggests that an intensive residential program for cancer survivors, as examined, was of no benefit.

To test the potential benefit of psychostimulants in managing fatigue in men with prostate cancer.

Patients were randomly assigned to receive methylphenidate or placebo for up to six weeks. Methylphenidate was started at 5 mg once daily and titrated upward by 5 mg every two to three days to a maximum of 30 mg/day. The physician or research nurse was in contact with each patient at least twice weekly for dosage and patient safety evaluation. Study data were collected at the time of study entry and at the end of the six-week study period.

• The study was comprised of 39 men with advanced prostate cancer receiving either chemotherapy or hormonal therapy.
• Mean age was 70 years (standard deviation = 9 years). 
• Of the patients, 90% were Caucasian, 71% were married, and 70% had a college education.
• Patients were eligible if they rated an average level of fatigue of 4 or greater on a 10-point scale over the past two weeks.
• Patients were excluded if they had cognitive impairment, major depression, or medical conditions or were taking medications that contraindicated use of a psychostimulant. 

• Single site
• Outpatient 
• Memorial Sloan Kettering

This was a randomized, double-blind, placebo-controlled, intervention study.

• Brief Fatigue Inventory (BFI)
• Fatigue Severity Scale (FSS)
• Hospital Anxiety and Depression Scale (HADS)
• Beck Depression Inventory (BDI)
• Functional Assessment of Cancer Therapy–Prostate (FACT-P)
• Systematic Assessment for Treatment of Emergent Events (SAFTEE) questionnaire

Of the eligible patients screened, 54% declined to participate. Of the patients in the methylphenidate group, 31% were discontinued due to increased blood pressure, and another 16% were removed due to tachycardia. The methylphenidate group showed significant reduction in BFI fatigue scores from 5.13 to 2.19 (p = 0.01). The placebo group also showed significant reduction in scores (p = 0.02). There was a difference between groups in the changes in fatigue during the study, with those in the methylphenidate group showing greater reduction in fatigue (p = 0.07; d = .80). There were no significant differences between groups in depression, anxiety, quality of life, or measures of cognitive function. The separation of study drug and placebo effects emerged at weeks 3 and 6.

The results suggested that methylphenidate was associated with a decline in fatigue; however, it was also associated with substantial cardiovascular side effects in almost half of the patients. A significant placebo effect was also observed.

• The study had a small sample size, with less than 100 patients. 
• There was substantial difficulty accruing patients for the study, and the sample was not sufficiently powered.

Psychostimulants may be helpful to some patients in managing fatigue, but their use should be accompanied by close monitoring of potential side effects.

The purpose of this study was to evaluate the dosage, effectiveness, and tolerability of an isopropanolic extract of black cohosh (Cimicifuga racemosa) in patients with breast cancer taking tamoxifen and reporting menopausal symptoms.   

The study drug, Remifenin, was dosed at 2 tablets by mouth per day (40 mg black cohosh total) for 4 weeks but then participants could self-escalate the dose per patient preference (20, 40, 60, or 80 mg) and continue daily tablets for up to 6 months (mean 134 days). Participants were assessed at baseline and again 3- and 6-months later (90 and 180 days later). A subset of 4 patients also took St. John’s Wort.

• 50 participants completed baseline, 47 completed first assessment, 40 secondassessment, and 35 final assessment. All available participants were used in the analyses.
• AGE:  Mean age of 56 years (range 43-77), no age SD reported.
• MALES (%)  0%    FEMALES (%)  100%
• KEY DISEASE CHARACTERISTICS:  All stages of breast cancer, estrogen receptor positive (n=44, 94%), metastases (n=4, 9%)
• OTHER KEY SAMPLE CHARACTERISTICS:  Mean of 8.6 months post diagnosis, 74% postmenopausal, 100% taking tamoxifen

• SITE: Single site   
• LOCATION: Germany
   

• PHASE OF CARE: Transition phase after initial treatment
• APPLICATIONS: Late effects & survivorship

Prospective, longitudinal, non-randomized study

• Menopause rating scale - self-assessment, profile and intensity of 11 menopausal symptoms, subscores for symptom domains of vegetative-somatic, psychic, and urogenital symptoms
• Physician documentation of tumor characteristics

There was a significant reduction in menopause rating scale scores, total scores, and subscales of vegetative-somatic and psychic symptoms at 1, 3, and 6 months of treatment. The overall MRS II score significantly decreased from 17.6 to 13.6 between baseline and last observation (p<0.001).   Two of the three symptom subscales also decreased significantly (vegetative-somatic and psychic both p<0.01).  However, the was no evidence of effectiveness for urogenital symptoms.  Symptoms that were initially most intense such as hot flashes, sweating, and sleep disturbances improved most during the observation period.

The effectiveness of black cohosh extract for treatment of menopausal symptoms among women taking adjuvant tamoxifen is still unclear.  Daily use over at least 4 weeks may result in reduced hot flashes and sleep disturbances.  The drug was well tolerated in the small sample; however, it is unclear what the ideal dosing is for therapeutic benefit.

Limitations of the study included:

• No appropriate control group
• Small, non-randomized study  
• 30% drop out rate over 6 months 
• Dosage varied
• Use of St. John’s Wort known to interfere with CYP450 isoenzymes and could have affected tamoxifen metabolism and the resulting side effects 
• Did not study possible impact on hormones
   

Black cohosh could be studied in a randomized trial but this study does not provide any efficacy information in relation to placebo. 

To evaluate the effectiveness of oral pyridoxine as prophylactic therapy for Palmar-Plantar Erythrodysesthesia (PPE)

The first 15 patients were treated without prophylaxis with oral pyridoxine. The following 20 patients were given oral pyridoxine 300 mg per day for 56 days.

• N = 35
• KEY DISEASE CHARACTERISTICS: Patients with locally advanced breast cancer
• OTHER KEY SAMPLE CHARACTERISTICS: Receiving pegylated liposomal doxorubicin (PLD) (15 mg/m² biweekly for four administrations) and paclitaxel (80 mg/m² weekly for eight administrations) as neoadjuvant chemotherapy

• LOCATION: Oncology unit at S. Salvatore Hospital in Pesaro, Italy

• Phase II study
  • Started in 2004

• Article discussed grade 1, grade 2, and grade 3 PPE

In group 1, 33% developed PPE—one patient developed grade 3, and four patients developed grade 2 PPE. In group 2, 40% developed PPE—three patients developed grade 3, and five patients developed grade 2 PPE.

Prophylactic use of vitamin B₆ may not be useful with biweekly administrations at low dose (15–20 mg/m²) because of low frequency of PPE documented with this particular schedule.

• Small sample size
• No randomization of patients
• Low doses of PLD
• Inadequate description of measurement tool/method to grade PPE symptoms; reliability and validity unclear