To assess the efficacy and tolerability of oral once-daily extended-release hydromorphone in the treatment of chronic cancer pain

The study period consisted of three phases. In the first, study participants were stabilized on previous opioid therapy. This phase lasted for at least three consecutive days on which the total daily dose remained unchanged and fewer than four rescue doses were taken. Visit 1 occurred in this phase. The second phase consisted of conversion to once-daily extended-release hydromorphone. Dose conversion was 5:1 morphine to hydromorphone, with a minimum starting dose of 8 mg hydromorphone. In cases of conversion from transdermal fentanyl, initial hydromorphone was 8 mg for each 25 mg/hour fentanyl. Phase 3 consisted of hydromorphone titration over 3–21 days Visit 2 occurred during phase 3. Each patient's dose was titrated in increments of 25%–100% of current hydromorphone dose. If not stabilized after 21 days, patients were discontinued from the study. Participants who achieved stabilization for 14 days were in maintenance phase (visit 3) and were treated on an outpatient basis through five study visits. Visit 4 was at the midpoint of the maintenance phase. Visit 5 was at the end of the phase. Immediate-release hydromorphone was available for the treatment of breakthrough pain.

The number of enrollees was 148. Of the enrollees, 127 patients received the study medication and 67% completed the study. Patients received at least 45 mg morphine and had stable analgesic requirements.

• Multicenter
• 30 sites throughout the United States and Canada

Open-label, repeated-dose, single-treatment study

• Short Form of the Brief Pain Inventory (BPI)
• Adverse events
• Scale comprising rankings of worst, least, and average, to measure pain intensity
• Scale, 0–10, to measure pain
• Scale, 0%–100%, to measure pain relief
• Scale, 0–10, to measure the extent to which pain interfered with activity, mood, walking, work, relationships, sleep, and enjoyment of life
• Scale, comprising five points, to measure patients' and investigators' perceptions of medication's overall effectiveness

Dose stabilization occurred in 119 of 127 patients (94%); 77% of patients achieved stabilization without titration. Mean BPI pain intensity and pain interference scores decreased significantly. Mean pain relief level remained stable after conversion and throughout treatment. Adverse events were as expected. Authors noted no clinically significant changes in vital signs. Of all patients, 87% received hydromorphone for seven days or longer; 40%, for 25 days or longer. Of all patients, 94% achieved dose stabilization. Mean time to dose stabilization was 3.6 days. Dose increased 38% from initiation to stabilization but decreased slightly at the end of the maintenance phase. Frequency of rescue medication declined. Ratings indicated a decrease in pain, but the decrease of pain intensity on average was the only significant pain-related statistic (p < 0.001). Decreases in pain intensity were accompanied by a significant decrease in pain interference scores for all categories (p < 0.05). Of all patients, 83% experienced adverse events (nausea, constipation, vomiting, diarrhea, and somnolence). Serious adverse events occurred in 20 patients (16%). Authors reported that only one of these serious adverse events, confusion accompanied by hallucinations, was due to hydromorphone. Four deaths occurred during the study, all due to disease, not treatment.

Patients with chronic cancer pain can easily undergo conversion from previous opioid to stabilization on once-daily oral extended-release hydromorphone. Authors noted that use of this form of hydromorphone offered acceptable clinical efficacy and safety and the convenience of once-daily dosing. Authors concluded that the 5:1 ratio conversion was effective and that the conversion was not a problem for most patients. Adverse events were consistent with those expected with the use of other opiods.

• The study had a risk of bias due to the open-label design and lack of control group.
• Patients’ previous opioid use was not standardized.
• The pharmaceutical and medical systems company Alza sponsored the study. Some investigators had conflicts of interest due to affiliation with pharmaceutical companies.

The study compared acupuncture tovenlafaxine for 12 weeks with health measurements for one year.

The enrolled 50 women, with 25 randomized to each arm. 

Inclusion criteria:

• Stage 0–III pre- or postmenopausal patients with breast cancer on hormone therapy with tamoxifen or arimidex
• 14 hot flashes per week
• 18 years of age
• May have been treated locally with surgery or radiation and must have completed chemotherapy
• May be receiving radiation therapy but otherwise must be within five years after treatment
• Must be on a stable dose of hormone therapy for four weeks or more without plans to discontinue therapy for the duration of the study
• Karnofsky performance status
• Life expectancy of at least six months

This was a randomized, controlled trial.

Participants completed:

• Hot Flash Diary (number and severity of hot flashes
• Menopause- Specific Quality of Life Questionnaire (MenQOL)

By two weeks after treatment, the venlafaxine group experienced significant decreases in hot flashes, and hot flashes in the acupuncture group remained at low levels. The venlafaxine group experienced 18 incidences of adverse effects (e.g., nausea, dry mouth, dizziness, anxiety), whereas the acupuncture group experienced no negative adverse effects. Acupuncture had the additional benefit of increased sex drive in some women, and most reported an improvement in their energy, clarity of thought, and sense of well-being.

Both groups exhibited significant decreases in hot flashes, depressive symptoms, and other QOL symptoms. Acupuncture was as effective as venlafaxine.

The study was limited by its small sample size.

To determine, by using a systematic review, which, if any, treatments have been found to be effective in reducing depression in patients with lung cancer

• Authors consulted these databases: MEDLINE (1948–Oct. 1, 2011), EMBASE Classic and EMBASE (1947–week 41, 2011), PsycINFO (1806–week 2, 2011), CINAHL Plus (1937–October 2011), and the Cochrane Central Register of Controlled Trials. Search keywords were depression, lung cancer, treatment, and systematic review.
• In this randomized controlled trial, adults were 18 years old or older and had received a definite diagnosis of lung cancer.
• The trial evaluated the efficacy or effectiveness of a pharmacologic or nonpharmacologic intervention intended to improve patients’ symptoms or quality of life. Depression outcomes were assessed using a standardized measure.
• Excluded from the analysis were nonprimary publications for which the full paper could not be obtained for data extraction.

The total number of references retrieved was 143. The evaluation method consisted of the review, by two independent researchers, of full articles.

• The final number of studies included was six.
• The sample range, across studies, was 64–549.
• Patients in the largest sample were newly diagnosed or new to the clinic; those in the smallest sample had a prognosis of 3–12 months. Most were from ambulatory clinics. Some patients had early-stage disease and some had metastatic disease.
   

• Phase of care: multiple
• Application: eldercare

No trials aimed to evaluate the effectiveness of treatments for depression in people with lung cancer. The six trials in the sample discussed interventions intended to improve symptoms related to quality of life, and each trial included a measure of depression as a secondary measure. The interventions, depression measures, and time of measurement varied. The interventions included breathlessness advice and discussion, education about self-referral for local psychosocial resources, counseling, coping skills training (including progressive muscle relaxation and symptom management strategies), early introduction of palliative care, and supportive psychotherapy. Studies indicated that enhanced care was more effective in reducing depression symptoms than was standard care.

Patients with lung cancer tend to be older adults with medical comorbidities, and these patients tend to suffer severe physical deterioration. Although standard depression treatments may be a reasonable course for treating depressed people with lung cancer, no randomized controlled trials (RCTs) guide clinicians in treating this population.

• The review was not limited to interventions designed specifically to treat depression.
• Participants were not necessarily depressed at the time of trial enrollment.
• Reviewers found that reports of the procedures for participant recruitment and the collection of outcome data frequently lacked detail.

No evidence guides clinicians who are caring for this specific population; well-conducted RCTs are urgently needed. Analysis indicates that clinicians may consider, as tools to reduce depression, depression treatments effective in older adults in the general population and those with medical comorbidities.

To assess the efficacy of an integrated treatment program for major depression in patients with lung cancer compared to usual care

Nurses were specially trained to deliver psychological interventions to patients who were physically deteriorating. The training emphasized the achievement of competency and included tutorials and role-play among other methods. The trained nurses provided 10 structured sessions with patients, usually in their homes, immediately following the diagnosis of depression. Additional treatment was provided by phone and, for those patients who did not meet targets, additional treatment was provided.

• N = 142  
• AVERAGE AGE = 63.8 years (range = 40.7–82.2 years)
• MALES: 35%, FEMALES: 65%
• KEY DISEASE CHARACTERISTICS: The majority of patients were diagnosed with lung cancer, and most of those diagnoses were non-small cell lung cancer.
• OTHER KEY SAMPLE CHARACTERISTICS: The majority of patients were retired and had a spouse or partner.

• SITE: Multi-site    
• SETTING TYPE: Outpatient    
• LOCATION: Scotland, United Kingdom

• PHASE OF CARE: Multiple phases of care
• APPLICATIONS: Elder care, palliative care

Randomized, controlled trial

• Hopkins Symptom Checklist (SCL-20) depression scale version B (20 items rated 0–4)

Average depression severity was significantly lower in patients allocated to the intervention group. Care was given by a nurse who usually visited patients in their homes. Depression improvement was self-rated. Improvement was seen in anxiety, quality of life, role functioning, perceived quality of care, and the proportion of patients achieving a 12-week treatment response.

In this study, the intervention proved to be more effective than usual care in reducing depression severity. Participants also saw improvements in anxiety, quality of life, and role functioning.

• Risk of bias (sample characteristics)
• Unintended interventions or applicable interventions not described that would influence results 
• Measurement/methods not well described
• Intervention expensive, impractical, or training needs
• Other limitations/explanation: Psychiatrists also prescribed medications. I was difficult to determine which parts of the intervention were effective.

To determine which treatments are effective for patients with diagnoses of both cancer and depression

TYPE OF STUDY: Systematic review

DATABASES USED: MEDLINE, EMBASE, EMBASE Classic, PsycINFO,Cochrane centeral register–all to 2012

INCLUSION CRITERIA: Randomized controlled trial, adult patients, cancer diagnosis, diagnosis of major depression, trial evaluated treatments for depression, depression outcomes were assessed with a standardized measure. Patients with additional psychological diagnoses were included if results were analyzed separately for depression.

EXCLUSION CRITERIA: None specified

TOTAL REFERENCES RETRIEVED: N = 8,442

EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Cochrane risk of bias tool used for quality evaluation

• N (studies) = 7
• SAMPLE RANGE ACROSS STUDIES: 46–200

Three trials of antidepressants were included. Two used mianserin, and one compared amitriptyline and paroxetine. One trial of mianserin showed superiority to placebo. No difference in depression outcomes was seen between amitriptyline and paroxetine. One trial of psychological treatment compared eight one-hour sessions of behavioral activation therapy with problem-solving therapy. No differences in depression outcomes were seen. One trial of combined antidepressants and psychological treatment showed better outcomes compared to usual care.

Limited evidence exists for treatment of depression among patients with cancer from this review. Limited evidence exists that antidepressant drugs alone or in combination with psychological treatments are effective.

Twenty-five trials were excluded because they did not use standard psychiatric DSM or ICD criteria for depression. Risk of performance bias was high, and other ratings of bias were deemed unclear. No studies included involved use of newer and more commonly used antidepressants.

This review provides little evidence regarding interventions that are effective for treatment of depression in patients with cancer.

To evaluate randomized, controlled caregiver-focused intervention studies intended to improve quality of life (QOL) in caregivers of adult patients with cancer

• Databases used for the search were MEDLINE, PsycINFO, EMBASE, CINAHL, and Cochrane Database Library.
• Studies were included that focused on patients with cancer and had presence of a caregiver (both age 18 or older); reported on a caregiver-targeted QOL measure; used randomization for intervention group assignment; reported on an intervention targeted to meet caregiver needs; and were English language.
• Studies were excluded if the full text of the article was unavailable; they reported on an uncontrolled, nonrandomized, patient-only targeted intervention; QOL was not measured; they included pediatric patients; and were qualitative or descriptive only.

• A total of 1,066 references was retrieved.
• A pair of independent raters first reviewed all abstracts for evidence of inclusion criteria, followed by final review for inclusion by the project leader.
• A second review again used two raters to assess each citation using an 11-item PEDro coding strategy, a Delphi method for randomized controlled trials (RCTs).

• Six studies were included.
• Sample (N = 1,115) range across studies was 30–329 caregivers.
• Study attrition rates were reported as 10.6%–54.7%.
• Mean caregiver age was 56.5 years.
• Approximately 82% of the caregivers were female (where reported).
• Patient cancer types included prostate, breast, or multiple cancer diagnoses across patients in one study.

Multiple phases of care

A variety of measurement instruments was used across the six studies, including the Caregiver QOL Index–Cancer in three studies, Functional Assessment of Cancer Therapy (version 3) and Short Form-36 Health Survey administered together in two studies, and Profile of Mood States–Short Form and Caregiver Strain Index administered together in one study. Two of six studies showed a statistically significant improvement in caregiver QOL at the first measurement interval. Effect sizes were available in four studies, with two showing no effect and two illustrating a small effect on caregiver QOL (Cohen’s d  = 0.264 [Northouse et al., 2007] and 0.271  [Walsh et al., 2007]). The Northouse et al. (2007) study also illustrated a small effect on caregiver coping (d = 0.392), self-efficacy (0.261), and negative appraisal (-0.191). Studies with interventions to improve caregiver ability to communicate and provide education on coping and specific care skills had the most impact.

High attrition rates in studies of the caregiver population were again noted, as are seen in other studies and reviews. The review included an evaluation of the effect of attrition on results and noted no significant impact on results, but it should be noted that the six studies included in this review were selected for their rigor.

The small sample was limited to RCTs of which there are few in the literature (not a fault of this study’s methodology).

More and larger controlled intervention studies are needed to clarify not only which interventions support QOL improvements, but under what circumstances and timing. The authors noted that different approaches may be needed when providing intervention to female versus male spousal caregivers to significantly improve depression. Attention to the optimal format and timing of interventions during phases when distress and need for support may be high, as well as attrition rates due to scheduling and general caregiving burden, is needed.

This randomized trial had two arms: alprazolam (0.5 mg) versus placebo. Dose increased over one week to 4 mg/day. Enrollment lasted four weeks.

The study reported on a sample of 36 inpatients and outpatients with cancer receiving treatment and/or follow-up.

• Single site
• Midwest teaching hospital

A randomized, controlled, double-blinded trial design was used.

• Hospital Anxiety and Depression Scale (HADS)
• Score > 7 on HADS and DSM-III criteria for anxiety, panic disorder, or adjustment disorder
• Hamilton Anxiety Rating Scale (HAM-A) (interviewer), Symptom Checklist–90-R (SCL-90-R) (self-rated)
• Hamilton Depression Rating Scale (HAM-D) (interviewer), Beck Depression Inventory (BDI) (self-rated)
• Global Rating Scale (GRS) (self-rated)

There was significant decrease in anxiety in both groups during week 1. There was no significant difference between alprazolam and placebo on anxiety for both self-rated and interviewer-rated scales.

• The study had a small sample size.
• The study points out that participation in a clinical trial may make one more susceptible to the placebo response.
• The average dose was only 1.2 mg/day; patients in study were unwilling to increase dose to therapeutic dosages.

To evaluate silver leaf nylon dressing (SLND) in preventing radiodermatitis in patients undergoing radiation therapy (RT) and concurrent chemotherapy.

• Fifteen consecutive patients with anal canal or gynecologic cancer were offered SLND as a preventive intervention.
• Selected patients were asked to wear SLND from day 1 of treatment until two weeks after the end of treatment.
• SLND was kept in place with thong underwear (and a pad as needed) and was kept moist as recommended by the manufacturer.
• Compliance in applying dressing was evaluated weekly by the treating physician.
• All patients were instructed to use soap and water on the perineum during a course of pelvic RT.
• The historical control group consisted of 12 patients from a prior institutional study that used conformal RT for anal canal cancer and three patients with gynecologic cancer who refused to participate in current study. Control patients used sulfadiazine at the occurrence of symptomatic dermatitis, per routine for the institution.
• Ten observers unaware of the treatment intervention were enrolled to evaluate skin changes.

• The sample was comprised of 15 patients using SLND and 15 historical controls.
• Age ranged from 38 to 92 years for SLND patients and 47 to 77 years for historical control patients.
• The SLND group included 10 women and 5 men, and the historial control included 11 women and 4 men.
• Patients had anal canal (n = 12) and gynecologic cancer (n = 3).
• Patients were undergoing combined external beam RT and chemotherapy.

Montreal General Hospital, Montreal, Quebec

The study was a phase 2, single-arm trial with a historical control comparison.

• No toxicity was associated with use of SLND, and no allergic reaction was documented in the patient cohort.
• During treatment, compliance was 100%.
• Two weeks after treatment, compliance was 70%—no wear was cited most frequently due to absence of symptoms.
• All patients completed treatment without interruption.
• There were three grade 3 scores in the SLND group compared with 92 grade 3 and 4 scores in the control group.
• Mean dermatitis score was 2.62 (standard deviation [SD] = 0.48) for controls. Mean dermatitis score for the SLND group was significantly lower at 1.16 (p < 0.0001).

The results suggest that SLND can be effective in reducing radiodermatitis.

• The study had a very small sample.
• Digital photography, although a useful tool, has not been evaluated in clinical studies.
• The study lacked random treatment assignment and used historical controls rather than a prospective design.
• In three female patients, patchy, moist desquamation was observed over the labia minora and around the urethra, an area not covered by the SLND—the effect of SLND is limited to immediate tissues in direct contact with dressing.
• The question of selective protection of normal tissues by the SLND could be raised. SLND was removed during RT.
• SLND is costly.

To compare the effectiveness, for women with a primary breast cancer, of experiential-existential group psychotherapy (incorporating cancer into one’s life) with that of a social-support group in regard to psychosocial adjustment (including psychological, psychosexual, and social adjustment); to examine the effect of age, type of surgery, and stage of disease on psychosocial adjustment indicators at the end of the intervention and at one year after the intervention

After the participants provided informed consent, they were randomly assigned to treatment groups: one group that received group psychotherapy; one group,  social support. Data were collected at baseline (T0), then the intervention groups were conducted for three months. Data were collected after the intervention (T1) and at 12 months after completion of the intervention (T2). The interventions consisted of 12 weekly sessions of 2.5 hours each, including a 30-minute coffee break. The two follow-up sessions were at one and two months after the close of the intervention groups. The two follow-up sessions involved only 6–10 women and were conducted by trained leaders. Two trained therapists led the experiential-existential groups, and two trained leaders led the social-support groups. The study method required at least one of the therapists or leaders in each group to be a woman. Each group psychotherapy session, except the 1st and the 12th, followed a specific structure: opening, discussion of a specific topic, choosing the topic for the following week, and closing the session. The first session focused on introduction of the procedures and getting to know others. The 12th session was used to evaluate the group, to discuss what was learned or missed, to suggest improvements, and to say goodbye. Participants were allowed to choose the topics of the two follow-up sessions.

• The sample was composed of 67 participants.
• Mean age of participants in each group was 49 years.
• All participants were female.
• Participants had breast cancer with no distant metastasis. No participant had a diagnosed psychiatric illness. In the psychotherapy group, 12 participants had had breast-conserving surgery; in the social-support group, 10. In the psychotherapy group, 21 had had mastectomy;  in the social-support group, 24.
• No significant demographic differences existed between intervention groups.
   

• Multisite
• Outpatient
• Several hospitals in Rotterdam, The Netherlands
   

• Phase of care: transition phase after initial treatment
• Clinical applications: late effects and survivorship
   

A time-series randomized clinical trial

• Emotional adjustment: Dutch version of the Profile of Mood States (POMS) scale   
• Psychosexual functioning: Sexual Functioning subscale of the European Organization for Research and Treatment quality of life questionnaire (EORTC QLQ-C30)
• Psychosexual functioning: Body Image subscale of the the EORTC QLQ-C30
• Social adjustment: Social Interaction subscale of the Sickness Impact Profile (SIP)
• Social adjustment: Recreation subscale of the SIP
• Demographic questionnaire
   

In regard to distress, vitality, sexual functioning, and social intentions, the psychotherapy group did not benefit more from the intervention than did the social-support group. At the end of the sessions, participants reported positive changes in regard to body image and recreation; the disease had less impact on recreational activities than on body image. Type of surgery was related to body image: Participants who had had breast-conserving surgery reported a more positive body image than did participants who had not.

Psychologically well-adjusted women diagnosed with breast cancer do not benefit from the interventions described in this study: experiential-existential group psychotherapy and social-support groups.

• The study has a small sample size, with fewer than 100 participants.
• The details of the therapies limit generalizability and raise questions regarding study replication.
• Decrease in the impact of disease on recreation could be a function of time.
• The drop-out rate seemed higher among participants who had had mastectomy than among those who had had breast-conserving surgery.
• Participants were psychosocially well adjusted at the beginning of the study, which may account for the minimal improvements shown.
• Only 27.5% of the women asked to participate in the study agreed to participate; 23% who began the study dropped out.
   

Results do not make clear whether support groups or group psychotherapy are beneficial for women who do not have substantial distress. In clinical practice, screening patients for psychological distress makes sense, as does providing therapy and the specified support interventions only to those patients who have distress and who may benefit.

The purpose of this systematic review was to compare the efficacy of pegfilgrastim primary prophylaxis (PPP) with current practice (CP [short course of treatment and not beginning in the first cycle]) neutropenia management in breast cancer.

MEDLINE, a clinical trial database at Amgen, and abstracts from the American Society of Clinical Oncology meetings from 2000–2005 were researched.

Key words were taxoids, (pegylated) doxorubicin, adriamycin, epirubicin, docetaxel, paclitaxel, cyclophosphamide, methotrexate, and fluorouracil combined with febrile neutropenia, neutropenia, leucopenia, and infection
 
Inclusion was based on English-language studies (randomized, controlled trials [RCTs], prospective observational studies, retrospective studies) on human subjects who received common breast cancer chemotherapy regimens associated with a febrile neutropenia risk 15% or greater. 

Studies were excluded if they had patients who received two weekly treatment cycles.

513 total references were retrieved.

The proportion of patients with febrile neutropenia across all cycles and the proportion of patients with febrile neutropenia in cycle 1, febrile neutropenia-related hospitalizations, chemotherapy dose delays of three or more days, dose reductions of 15% or greater, and grades 3 and 4 hematologic toxicities. An integrated analysis was conducted on individual patient data. Descriptive summaries of demographic information and disease characteristics for individual and integrated populations within each group (PPP versus CP). G-CSF was characterized by administration. For the comparative analysis homogeneity of patient populations within each group and then between each group was evaluated. A generalized linear mixed model was fitted for the outcome of febrile neutropenia across all cycles and for cycle 1 per type of prophylactic treatment (PPP or CP). Other variables in the model included age, disease stage, and prior chemotherapy/radiation treatment. Variables were adjusted using the least square means. Sensitivity analyses also were conducted. Studies that included G-CSF given within seven days of the last chemotherapy dose in cycle one were removed for the CP group in the analysis.

• 19 studies were included in the final review.
• The sample range across studies was 7–927 participants
• 2,282 total patients were included in this review (1,303 PPP and 979 CP)
• Female patients with breast cancer who received chemotherapy treatments with an associated 15% or greater risk of febrile neutropenia.
• The majority of patients were older than age 50 years, were Caucasian, and had an ECOG status of 0 or 1.
• The majority of patients also had a stage II, III, or IV diagnosis and most had not had prior therapy.
• 981 patients had an unknown estrogen receptor status, 564 were receptor negative, and 737 were receptor positive.
• 338 patients had adenocarcinomas, and the histology was unknown for the remaining patients.
• Chemotherapy regimens varied and included doxorubicin, cyclophosphamide, carboplatin, doecetaxel, epirubicin, and paclitaxel.

Active treatment

The incidence of febrile neutropenia for all cycles and in cycle one were lower in patients who received PPP compared to those who received CP (p < 0.0001). An increased risk of febrile neutropenia was found for older patients and for those with stage IV disease. Hospitalizations associated with febrile neutropenia also were lower for the PPP group compared to the CP group. Grades 3 and 4 neutropenia were lower in the PPP group (47%, 95% CI [9%, 89%]) compared to the CP group (96%, 95% CI [70%, 99%]) adjusted rates and similarly for leucopenia were also lower in the PPP group (47%, 95% CI [15%, 82%]) compared to the CP group (94%, 95% CI [74%, 99%]).

The use pegfilgrastim primary prophylaxis for the prevention of febrile neutropenia, grades 3 and 4 neutropenia, and neutropenia-related hospitalizations is more effective than current practice use of G-CSF (short course of treatment and not beginning in the first cycle) for patients receiving myelosuppressive chemotherapy for treatment of breast cancer.

Oncology nurses can advocate for the use of PPP for this patient population.