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.

The aim of the study was to evaluate the safety and efficacy of pregabalin in the management of chemotherapy-induced neuropathic pain.

Children were medicated with pregabalin twice daily starting at 75 mg per day and titrated upwards by 75 mg daily with doses ranging from 150–300 mg for eight weeks. No patient was receiving chemotherapy at the time of pregabalin administration. Patients were evaluated prior to treatment and at weeks 2, 4, 6, and 8 of treatment using a visual analog scale. Patients were asked about side effects.

• The total sample size was 28 (19 females, 11 males).
• Age ranged from 10–17 years; mean age was 13.5 years.
• The participants had been diagnosed with childhood solid tumors and leukemia.
• The participants had been treated with platinum and/or vinca alkaloids and developed peripheral neuropathy.
• No other drug was used for neuropathic pain.

The study was conducted at a single outpatient setting in the Czech Republic.

The study had a prospective trial design.

Visual analog scale

The mean visual analog scale score decreased by 59% from baseline during eight weeks of pregabalin with statistically significant improvement in pain symptoms (p < 0.001). A marked pain relief was noted in 14, moderate pain relief in 10, mild pain relief in two, and no pain relief in two patients. Adverse effects were mild or moderate.

Pregabalin appears to be safe and effective in treating pediatric patients with cancer suffering from chemotherapy-induced peripheral neuropathy. Pregabalin has mild to moderate adverse effects.

• The sample size was small (less than 30).
• The study lacked a comparison or control group.
• Measurement of pain was conducted with one scale.
• The patient population age limits the ability to generalize findings to the adult cancer population.

Pregabalin has been shown to be effective in relieving pain from chemotherapy in pediatric patients; however, pregabalin is expensive and a controlled drug. Preagabalin has mild to moderate side effects and was tolerated without major complications.

To evaluate the efficacy of memory and speed of processing training for improving cognitive function in breast cancer survivors

Patients were randomly assigned to one of three groups: training in speed of processing, memory training, or a wait list control group. The intervention included 10 one-hour sessions of memory and speed of processing training delivered in small groups of three to five patients over six to eight weeks. Specific intervention strategies were adapted from the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) trials. Follow-up was done at two months.

• A total of 82 patients participated in the study.
• Participants' mean age was 56.6 years (SD = 8.5 years).
• The sample was 100% female.
• All patients were diagnosed with breast cancer and had received surgery and chemotherapy. The mean time since treatment was 5.5 years.

• Single site
• Outpatient setting
• United States

Patients were in the late effects and survivorship phases of care.

Single-blind, three-group randomized controlled trial

• Rey Auditory Verbal Learning Test
• Rivermead Behavioral Paragraph Recall test
• Useful Field of View for speed of processing
• Functional Assessment of Cancer Therapy–Cognitive (FACT–Cog)
• Squire Subjective Memory Questionnaire
• Center for Epidemiological Studies Depression Scale
• Spielberger State–Trait Anxiety Inventory
• FACT–Fatigue
• Quality of Life Cancer Survivors
• Short Form-36

The memory training group demonstrated better immediate (d = 0.59, p = 0.036) and delayed memory performance (d = 0.70, p = 0.013) at the two-month follow-up compared to the control group. Those trained in speed of processing improved immediate memory post-intervention (d = 0.75) and at the two-month follow-up (d = 0.82) (p < 0.01). The memory and speed of processing training groups had significant improvement in perceived cognitive functioning on questionnaires. Compared to controls, speed of processing training was associated with lower symptom distress. Memory training also had a positive effect on anxiety at the two-month follow-up (p = 0.017)

Memory and speed of processing training had significant positive effects on objectively measured and perceived cognitive function among female breast cancer survivors.

• The sample was small at less than 100.
• A lack of blinding and no appropriate attentional control condition introduced a risk of bias.
• The findings not generalizable because of the highly specific sample group. The findings may not be applicable to other groups of patients or at other time points in the cancer trajectory.
• The training needs to be delivered by individuals educated in the process.

Cognitive training as provided here had a significant and at least a moderate positive effect on cognitive function in breast cancer survivors. Cognitive deficits with cancer treatment have substantial negative impacts on quality of life and functioning. Cognitive training is a promising intervention to address these problems.

The purpose of the study was to compare rates of febrile neutropenia between four treatments: (a) ciprofloxacin 500 mg PO BID on days 5–14, (b) G-CSF (filgrastim 5 mg/kg per day or lenograstim 150 mg/m² per day) on days 5–10, (c) pegfilgratim 6 mg on day 2, and (d) pegfilgrastim plus ciprofloxacin.

A secondary aim was to compare the incidence of neutropenia and other hematologic toxic effects, infection, nonhematologic toxic effects, and hospitalization.

Patients enrolled in the German GeparTrio study from April 2001 and June 2005 who received one of the four neutropenia prophylactic regimens were analyzed. Patients analyzed had completed at least one cycle of TAC and were not randomized to no treatment.

• 1,256 participants were enrolled.
• All were aged 18 years or older
• All were female
• All were diagnosed with breast cancer

89 outpatient sites in Germany

Active treatment

Retrospective cohort study of women with breast cancer enrolled in the Germany GeparTrio study.

• Febrile neutropenia
• Grade 4 neutropenia
• Hematologic toxicities (leukopenia, anemia [hemoglobin lower than 10 g/dl], thrombocytopenia)
• Hospitalizations
• Non-hematologic toxicities (infection without neutropenia, stomatitis, dysphagia/esophagitis, diarrhea)
   

Among the 1,256 patients in the analyses, 1,057 completed all planned cycles of treatment (six cycles, n = 793; eight cycles, n = 264). The combination of pegfilgrastim and ciprofloxacin was statistically significantly better than other regimens for the prevention of overall febrile neutropenia (p < 0.001), febrile neutropenia during the first chemotherapy cycle (p < 0.001), lower incidences of grade 4 neutropenia, prevention of leukopenia and anemia (p < 0.001), fewer hospitalizations (p < 0.001), and for the reduction of stomatitis/mucositis, dysphagia/esophagitis, and diarrhea. Pegfilgrastim alone was as effective as pegfilgrastim and cipro for overall febrile neutropenia (p < 0.001) and for the reduction of grade 4 neutropenia, leukopenia, and anemia (p < 0.01). Daily G-CSF was better than cipro alone for the reduction of grade 4 neutropenia. Thrombocytopenia was lowest for cipro alone (p < 0.001). Infection with neutropenia was not statistically different between groups.

The use of pegfilgratim, especially in combination with ciprofloxacin, is superior to ciprofloxacin alone or daily G-CSF for the reduction of febrile neutropenia, grade 4 neutropenia, and related hospitalizations. No regimen proved superior over others for the prevention of infection with neutropenia.

The administration of daily G-CSF was not given according to protocol of beginning 24 hours after the last dose of chemotherapy with continuation until absolute neutrophil count (ANC) has returned to normal range or for a maximum of 14 days. G-CSF was started at a later time in the cohorts who received G-CSF which could have skewed the results in favor of pegfilgrastim, which was given according to protocol.

The use of pegfilgratim, especially with ciprofloxacin, for the prevention of febrile neutropenia, grade 4 neutropenia, and neutropenic-related hospitalizations appears beneficial for women with stage T2–T4 primary breast cancer. Oncology nurses can advocate for use of this regimen for their patients.