To illuminate the moderators of the effect of psychosocial interventions and better understand the variability of these effects in patients with cancer; to test the hypothesis that cancer type, intervention type, and interventionist can moderate intervention effect

• Databases searched were PsycINFO, PSYNDEX, MEDLINE (1980–October 2004). Search keywords were cancer, neoplasm, carcinoma, oncology, breast cancer, psychological therapy, psychotherapy, intervention, counseling, group support, peer support, relaxation, imagery, coping skills training, cognitive therapy and psychological support. Investigators also did some manual searching, using references from retrieved articles.
• In cases in which the literature reported incomplete outcomes, investigators communicated with the authors of the studies to get the data. Some authors provided the necessary data.
• Literature included in the meta-analysis reported, in English or German, on randomized controlled trials (RCTs) and provided complete documentation of outcome measures.
• Literature excluded from the meta-analysis did not report on an RCT or did not include complete data, including the sample sizes of the treatment and control groups; group means; standard deviations or values of t tests, F tests, and chi-square tests.

Initially, investigators retrieved 127 articles, of which 46 were eliminated because they did not report on RCTs. Four of the 127 articles were unavailable. Of the remaining 77 reports of RCTs, the data in 26 were incomplete. Communication with the authors of studies with incomplete data resulted in obtaining complete data for five studies.

• The final number of studies included in the meta-analysis was 56. Sample range was 19–638.
• Meta-analysis, across studies, included a total of 6,419 patients. Mean patient age was 52.4 years (SD = ±4.7 years), and the age range was 40–65 years. The majority of study participants  (89%) were female.
• Studies in the meta-analysis were conducted in the United States or in multiple European countries. Thirty-four studies involved a homogeneous group of patients with breast cancer, and 22 studies involved mixed diagnoses.

• Across all studies, effect size (ES) d = –0.47–2.66; overall average, ES d = 0.56.
• Types of interventions were as follows. Some studies involved more than one treatment group.
  • Psychoeducational (EDU): 8 studies (ES/d = 0.53).
  • Cognitive behavioral therapy (CBT): 24 studies (ES/d = 0.19).
  • Supportive therapy (SUP): 15 studies (ES/d = 0.13).
  • Relaxation (REL): 12 studies.
• Moderator effects were as follows.
  • The majority of studies were led by psychologists (n = 21) or nurses (n = 11). Psychologist-led interventions had a higher ES (d = 0.30) than did those led by nurses (d = 0.15) (p < 0.001).
  • Nature of the control group in studies was identified as active if active interventions of some type were delivered. The control group was identified as passive if controls received usual care or were wait-listed. Passive control groups had higher ES (d = 0.34) than did those with active controls (d = 0.11) (p < 0.001).
  • Formats of the intervention were individual, group, couple, self-help, and patient with family-member. Comparison between group and individual formats showed higher ES for individual interventions (d = 0.30) than for group interventions (d = 0.19) (p < 0.001).
  • Timing of the intervention was reported in 82% of studies. Timing options were directly after diagnosis or surgery, during or following chemotherapy or radiation therapy, and months or years after initial diagnosis. Interventions conducted directly after diagnosis or surgery (d = 0.33) had higher ES than did those during treatment (d = 0.18) or those conducted months or years after diagnosis (d = 0.16) (p < 0.001).
  • Patients with early-stage (I–III) disease had higher ES (d = 0.32) than those with advanced disease (d = 0.13) (p < 0.01).
  • For EDU, moderate ES (d = 0.73) resulted if the intervention had been conducted by nursing or medical staff rather than by psychologists. Psychologist-delivered ED resulted in small ES (d = 0.27).
  • CBT resulted in moderate ES (d = 0.40) if conducted by psychologists. CBT resulted in no effects if nurses or social workers delivered the intervention.
  • Authors found no difference in the results of interventions delivered by different SUP interventionists.

• Psychosocial interventions of various types can have a positive effect on patients with cancer.
• Psychoeducational interventions appear to have the greatest effect, and this effect is higher when the education is delivered by professionals with medical expertise than when delivered by others.
• Interventions appear to be most effective in cases of early-stage disease and when delivered early in the phase of care.
• Individualized interventions appear to have an effect that is greater than interventions delivered in groups.

• The quality of individual studies included was highly variable.
• Some studies provided actual data on significant findings only, although the studies had measured several outcomes. As a result, the ES reported in this meta-analysis may be somewhat overestimated.
• Long-term effects of intervention types are still unclear because most studies did not include long-term follow-up.

Nurses are particularly suited to providing psychoeducational and educational interventions for patients, and these types of nurse-led interventions can have a positive effect on patient outcomes. Psychologist-delivered CBT interventions seem to be more effective than nurse-delivered CBT interventions. This finding suggests that, if nurses are to provide CBT, the nurses must develop significant expertise.This finding may also suggest the importance of interdisciplinary approaches to providing psychosocial interventions. This meta-analysis demonstrated that moderators have a significant effect on intervention effectiveness; therefore, future studies should provide information about potential moderators.

To obtain data to support conducting a phase III trial of venlafaxine to prevent oxaliplatin-induced neurotoxicity

Patients were stratified according to planned calcium and magnesium administration, cancer stage, and treatment cycle, then randomized to receive venlafaxine extended release 37.5 mg versus placebo twice daily. The study treatment was begun on the evening of the first or second chemotherapy treatment and continued for one week following completion of the FOLFOX treatment. Assessments were taken at baseline, prior to each FOLFOX treatment, and at 1, 3, 6, and 12 months postcompletion.

• N = 43
• MEAN AGE = 61.3 years
• MALES: 52%, FEMALES: 48%

• SITE: Multi-site  
• SETTING TYPE: Not specified  
• LOCATION: USA

PHASE OF CARE: Active antitumor treatment

Randomized, double-blind, placebo-controlled trial

• European Organization for Research and Treatment of Cancer (EORTC) Quality of Life (QLQ)-CIPN20 symptom questionnaire
• Common Terminology Criteria for Adverse Events (CTCAE), version 4.0
• Oxaliplatin Acute Symptom Questionnaire

No significant differences in any measures of neuropathy outcomes existed between groups.

Venlafaxine did not reduce neuropathic toxicities associated with oxaliplatin.

Small sample (< 100)

Data from this trial do not support the use of venlafaxine for the prevention of neuropathic symptoms associated with oxaliplatin. Ongoing research is needed to identify effective interventions for this treatment complication.

To evaluate effectiveness of manual lymphatic drainage (MLD) for prevention of secondary lymphedema after breast cancer surgery

From the second post-operative day, women received a standard program of exercises. Thirty-three women were randomly chosen to also receive MLD five times a week for the first two weeks, then twice a week until six months after surgery. The other control group women applied self-drainage. Data were collected prior to surgery and at six months postoperatively. Arm volume measurements were done on days 2, 7, 14, and 3 and 6 months.

• The study sample (N = 67) was comprised of female patients with breast cancer.
• Mean age was 59.4 years.
• In the sample, 80% had breast conserving surgery and 40% had modified radical mastectomy; 52% had axillary lymph node dissection.
• In the control group, 74% had radiotherapy, compared to 67% in the MLD group. 
• More women in the control group also received other adjuvant therapy, compared to the MLD group.

The study took place at a single outpatient site in Poland.

The patients were undergoing multiple phases of care.

The study used a prospective trial design.

Water displacement was used to measure arm volume.

Women in the MLD group showed a reduction of 14 ml volume (SD = 470 ml) on the operated-side arm over six months. Women in the control group showed an overall increase in arm volume of 16 ml (SD = 470, p = 0.0033). Analysis of variance showed significant effect of having MLD (p = 0001) and radiotherapy (p = 0.0499) on arm volume.

Findings showed that use of MLD may have some benefit for prevention of lymphedema secondary to breast cancer surgery. Several study limitations suggest that findings should be used with caution.

• The sample size was small, with less than 100 participants.
• The baseline sample and group differences could influence results.
• The study had a risk of bias because of no binding and no random assignment.
• The ample included various surgical types. 
• It is not clear that patients were randomly assigned to groups. 
• Adherence to MLD and self-management are not discussed, and no other interventions that may affect lymphedema are discussed. 
• The control group had a higher percent of women receiving radiotherapy, which was shown to predict arm volume increase.
• There was high variability in arm volume results in both groups compared to mean changes observed.

Findings of the study do not provide strong support for effectiveness of MLD to prevention lymphedema after breast surgery because of the multiple study design and results limitations.

To test the effect of bupivacaine, applied in the area of surgical incision, on the pain experienced by postmastectomy patients; to see how the bupivacaine affected use of analgesics  

Before mastectomy, women were randomized to receive bupivacaine application or saline placebo. The bupivacaine group received 100 mg bupivacainum hydrochloricum dissolved in normal saline. The control group received normal saline. Bupivacaine and saline were administered in the same way: subcutaneously, along the intended line of incision, 15 minutes before the operation. All patients received standard oral premedication: 7.5 mg midazolam. Anesthesia consisted of propofol, 2 mg/kg body weight; vecuronium, 0.6 mg/kg; and fentanyl, 2 mcg/kg. After surgery, each patient had the option of patient-controlled analgesia, which consisted of standard drug concentrations based on body weight. IV metamizole, 1g, was administered every 6 hours. Pain was measured at 1, 2, 3, 4, 8, 12, 16, 20, 24, 36, and 48 hours postoperatively. Total analgesic consumption was recorded.

• Authors included 106 patients in the intention-to-treat analysis.   
• Mean patient age was 59.4 years. The age range of patients was 24–83 years.
• All the patients were female.
• All participants had stage I–III breast cancer.
   

• Single site
• Inpatient
• Poland
   

Active treatment

Randomized double-blind placebo-controlled trial

Visual analog scale (VAS), with a 0–10 scale, to measure pain severity

Compared to patients receiving placebo, patients receiving bupivacaine reported significantly lower pain severity at the 4th (p = 0.004) and 12th  p = 0.02) postoperative hours. Patients receiving bupivacaine used less fentanyl (p = 0.011). Between the 4th and 12th postoperative hours, those receiving bupivacaine used less PCA morphine (p = 0.02) than did the control group. The pattern of VAS scores was similar in both groups, with a spike in pain during the first postoperative hour and a gradual decline thereafter. Across the first 12 hours, pain scores in the bupivacaine group were consistently lower than the scores in the control group. Authors noted no differences between groups in regard to time to first morphine dose or total amount of morphine used during the postoperative follow-up.

Preoperative subcutaneous injection of bupivacaine to the site of surgical incision was effective in reducing patients' pain severity and morphine consumption during the first 12 hours after mastectomy.

• Authors provided very little disease-related or demographic information about the sample. 
• Authors provided no information about variation in the extent of the surgical procedure, patient to patient.
• Median pain scores reported for both groups were 0 at individual hourly time points. This raises the question of the actual clinical relevance of findings.
• Analysis was sometimes based on VAS scores and sometimes on nonquantitative variables.

Findings provide support for the use of bupivacaine injection to relieve postmastectomy pain. Nurses can advocate for consideration of this approach as part of surgical pain management. Note that these results are not immediately generalizable to other surgical populations.

Patients with chemotherapy-induced diarrhea (CID) refractory to loperamide received 100 mcg subcutaneous octreotide three times per day for three days followed by 50 mcg three times per day for three days. The median time between chemotherapy and starting octreotide was 8 days (range = 5–9 days).

• The study reported on 32 patients from two cancer centers with grade 2–3 CID (according to World Health Organization [WHO] classification) refractory to loperamide.
• Chemotherapy regimens were 5-fluorouracil (5-FU) and leucovorin (n = 19): irinotecan, 5-FU, and leucovorin (n = 4); 5-FU combination including one or more of cyclophosphamide, epirubicin, cisplatin, methotrexate, and cisplatin (n = 8); and 5-FU combination plus radiation therapy (n = 1).
• Primary tumors were colorectal (23), gastric (3), and other (6).
• Patients initially had received 4 mg loperamide followed by 2 mg every six hours for 48 hours.

This was a prospective study.

Patients recorded the number of bowel movements. Complete response (CR) was defined as no diarrheal stools per day; partial response (PR) was defined as 1–2 diarrheal stools per day; and no response was defined as three or more diarrheal stools per day. Progression was defined as an increase in the number of diarrheal stools.

• The majority of patients (94%) experienced CR. Five patients experienced CR within 24 hours; 14 within 48 hours; and 11 within 72 hours.
• Twelve of the patients who experienced CR discontinued treatment after three days because they reported feeling \"very healthy.\"
• No toxic side effects were documented.

Octreotide was found to be highly effective as second-line therapy in managing patients with CID. 

The sample size was small.

To identify improvement in fatigue, sleep, and quality of life in breast cancer survivors using self-administered acupressure

Self-administered relaxing acupressure or stimulating acupressure performed once daily for three minutes for six weeks. Assessments were conducted at baseline, three weeks (to assess technique), six weeks (end of intervention), and 10 weeks (washout).

• N = 288   
• AGE = Not stated
• FEMALES: 100%
• CURRENT TREATMENT: Not applicable
• KEY DISEASE CHARACTERISTICS: Stage 0-III breast cancer
• OTHER KEY SAMPLE CHARACTERISTICS: Patients who had reported fatigue, completed chemotherapy or radiation 12 months prior, and were cancer-free

• SITE: Single-site   
• SETTING TYPE: Home    
• LOCATION: Michigan

• PHASE OF CARE: Late effects and survivorship
• APPLICATIONS: Elder care, palliative care 

• Phase III, randomized, single-blind trial
• Computer-generated randomization 1:1:1 (relaxing acupressure, stimulating acupressure, usual care)

• Brief Fatigue Inventory (BFI)
• Pittsburgh Sleep Quality Index (PSQI)
• Long-Term Quality of Life Instrument (LTQL)

• At six weeks, improvement in BFI for both relaxing and stimulating acupressure over usual care was observed (p < 0.001). No difference between the relaxing and stimulating groups existed. At 10 weeks, improvement in BFI for both relaxing and stimulating acupressure over usual care was reported (p < 0.001), and no difference between the acupressure groups existed. Both acupressure groups achieved normal fatigue levels versus usual care at weeks 6 and 10 (p < 0.001).
• An improvement in PSQI score in the relaxing acupressure group was observed compared to the stimulating group and usual care group at week 6, and no difference between groups existed at week 10. 
• An improvement in quality of life scores at weeks 6 and 10 in the relaxing acupressure group was reported.

Self-administered relaxing and stimulating acupressure may improve fatigue in breast cancer survivors who have completed treatment at least 12 months ago. Relaxing acupressure may also improve sleep and quality of life in this patient group.

• Key sample group differences that could influence results
• Intervention expensive, impractical, or training needs
• Limited to breast cancer survivors who were one year post treatment in one state
• Lack of diversity in population studied
• Staff need to be trained in acupressure to train patients.

Self-administered relaxing and stimulating acupressure may be beneficial in the reduction of fatigue in breast cancer survivors who have completed treatment at least 12 months ago. Additional studies could be conducted with those currently receiving treatment and with patients with other cancers.

To evaluate the efficacy of ginger in relief of delayed chemotherapy-induced nausea and vomiting (CINV)

Patients with cancer who had experienced CINV during at least one previous round of chemotherapy were asked to participate. All participants were receiving a 5-HT₃ receptor antagonist or aprepitant as part of their standard antiemetic regimen. Patients were randomized to receive either 1.0 g of ginger, 2.0 g of ginger, or matching placebo daily for three days.

• The study consisted of 162 participants.
• The mean age was 55.7 years.
• The majority of the participants was female.
• Specific diagnoses were not stated.
• Patients were receiving a variety of chemotherapy drugs of low, moderate, and high emetogenic risk.

The study was conducted at multiple outpatient settings in Ann Arbor, MI.

All patients were in active treatment.

This was a randomized double-blind, placebo-controlled trial.

The Morrow Assessment of Nausea and Emesis (MANE) and the National Cancer Institute (NCI) Common Toxicity Criteria version 3.0 for Adverse Events were used.

• More than half (58%) of study participants reported experiencing both acute and delayed nausea; 30.9% reported acute vomiting or retching; and 24.7% reported delayed vomiting or retching.
• No significant difference was found between either of the ginger doses compared to placebo in the terms of acute or delayed nausea or vomiting. This was consistent when participants were stratified by whether  aprepitant was prescribed as part of their CINV treatment.
• Participants who received the higher dose of ginger (2.0 g) reported having significantly more severe episodes of delayed nausea compared to both placebo and low-dose ginger.

• Ginger extract provided no benefit in reducing prevalence of delayed nausea and vomiting when added to standard contemporary antiemetic therapy.
• When ginger was taken with aprepitant, prevalence of delayed vomiting was higher (although this did not reach statistical significance).

• The study lacked an adequate sample size.
• Participants reported that they knew if they were randomized to either of the ginger treatment arms based on the taste of the capsule.

Ginger extract provides no clinical benefit at the doses evaluated when given in addition to standard, evidence-based medical therapy to prevent CINV. Ginger extract may have a negative effect on severity of nausea when taken with aprepitant.

To estimate the impact of antifungal prophylaxis on the occurrence of proven systemic fungal infections in patients with neutropenia and to quantify its effect on mortality attributed to these infections.

Databases searched were MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials through September 15, 2010.  In addition, proceedings of the annual meetings of the Infectious Diseases Society of America (2001–2009), the American Society of Hematology (2000–2009), and the European Society of Clinical Microbiology and Infectious Diseases (2000–2010) were manually reviewed.

Search keywords were clinical trial(s), neutropenia, neoplasms, malignant, malignant neoplasm, mycoses, candida, aspergillus, zygomycosis, antifungal agents/antifungal, ketoconazole, fluconazole, itraconazole, voriconazole, posaconazole, amphotericin B, miconazole, and micafungin.

Articles were included if they focused on patients undergoing treatment for cancer who received prophylactic antifungal medications.

Articles were excluded if they directly compared systemic antifungal prophylactic agents, evaluated nonabsorbable polyenes or oral antifungal formulations of amphotericin B, and did not evaluate antifungals prophylactically (i.e., those that included empirical, pre-emptive, or salvage therapies for fungal mycoses).
 

A total of 11,418 references were retrieved.

A meta-analysis method of study was used. In specific, statistical analysis was performed to compare study results, including effects of antifungal prophylaxis using random effects and reported as pooled odds ratios (ORs) and 95% confidence intervals (CIs) using the Robins-Breslow-Greenland formula.  For study cells with zero events, an ad hoc treatment arm continuity correction was used.  Findings in which the 95% CI crossed 1 were not considered statistically significant. Statistical heterogeneity was assessed using the I² statistic and Cochrane Q test. The Petro method was used for sensitivity analysis, and the Harbord modification of the Egger test was used to evaluate small study effects for major outcomes.

• After exclusion factors, 26 articles remained in total and 25 were included in the analysis of the outcomes.  
• The total sample across all articles was 3,979.
• Sample sizes per article ranged from 25 to 405.
• Median age ranged from 7 to 65 years across studies. The majority of patients had hematologic malignancies treated with or without hematopoietic stem cell transplantation (HSCT), and five studies included patients with solid tumors. Specific diagnoses were not disclosed.

Patients were undergoing the active treatment phase of care.

Antifungal prophylaxis was associated with statistically significant reductions in proven fungal infections (OR = 0.43; 95% CI [0.31, 0.6]; number needed to treat [NNT] = 20) and mortality attributed to fungal infections (OR = 0.49; 95% CI [0.3, 0.8]; NNT = 53), reduction in risk for proven candida infections (OR = 0.28; 95% CI [0.2, 0.38]), and a decreased need for antifungal therapy (OR = 0.64; 95% CI [0.48, 0.86]). Explanatory subanalysis of major outcomes showed a reduced risk for proven infections among HSCT recipients only (OR = 0.27; 95% CI [0.16, 0.44]) and infection-related mortality (OR = 0.41; 95% CI [0.21, 0.81]). Not statistically significant were overall mortality (OR = 0.92; 95% CI [0.74, 1.14]) or reduction of aspergillosis or zygomycosis. Meta-regression analysis showed that multi-center and double-blind designs were significant moderators of the effect of antifungal prophylaxis on overall mortality and proven systemic fungal infections.

Systemic antifungal prophylaxis was associated with decreased proven fungal infections and fungal infection-related mortality in patients with neutropenia following chemotherapy.  Antifungal prophylaxis was also associated with decreased proven infections and infection-related mortality in HSCT recipients.  Overall mortality was not improved through the use of antifungal prophylactic therapy.

 The use of prophylactic antifungal therapy should be considered for patients receiving neutropenic-inducing chemotherapy and/or those undergoing HSCT.

RESOURCE TYPE: Consensus-based guideline

PROCESS OF DEVELOPMENT: Asian expert panel of head and neck cancer specialists

PHASE OF CARE: Active treatment

• Multinational Association of Supportive Care in Cancer (MASCC) guidelines
• World Health Organization (WHO) and Common Terminology Criteria for Adverse Events (CTCAE) for toxicity grading of oral mucositis
• Annals of Oncology
• The Bonner trial (Radiotherapy plus cetuximab for locoregionally advanced head and neck cancer: 5-year survival data from a phase 3 randomized trial, and relation between cetuximab-induced rash and survival. Published in Lancet Oncology in 2010)

This review and expert opinion were limited to patients with head and neck squamous cell carcinoma undergoing radiation therapy with or without cetuximab or chemotherapy. The authors’ proposal of a new grading system was noted to be adapted from the authors who previously addressed the need for a new grading system.

STUDY PURPOSE: To determine the efficacy and safety of zoledronate in treating pain related to metastatic bone disease

TYPE OF STUDY: Meta-analysis and systematic review

DATABASES USED: PubMed, EMBASE, and the Cochrane Library up to October 2011

KEYWORDS: Zoledronic acid and bone metastasis, and these two terms in combination with zoledronate and bone pain

INCLUSION CRITERIA: Patient had at least one site of bone metastasis; Eastern Cooperative Oncology Group performance status of 2 or less; the study evaluated the effects of at least one type of zoledronate on skeletal-related events (SREs) or bone pain in patients with any type of metastatic bone disease; study was a placebo-controlled RCT; and study reported Brief Pain Inventory (BPI) scores at all time points examined

EXCLUSION CRITERIA: None listed

TOTAL REFERENCES RETRIEVED = 150 studies

EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Two reviewers used the Jadad composite scale to score the methodologic quality of the studies for the studies that were included in the analysis

• FINAL NUMBER STUDIES INCLUDED = 12
• SAMPLE RANGE ACROSS STUDIES, TOTAL PATIENTS INCLUDED IN REVIEW: 4,450 patients (range of sample size = 20–440)
• KEY SAMPLE CHARACTERISTICS: No key sample characteristics listed

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

Ten of the 12 RCTs provided data on SREs. Patients receiving zoledronate had a significantly lower rate of SREs than the placebo group (RR 0.75, 95% Cl 0.69–0.81, p < 0.001). Six studies that reported BPI scores found the zoledronate group to have significantly reduced scores at three months (WMD -0.53, 95% Cl -0.72–-0.35, p < 0.001), 12 months (WMD 0.39, 95% Cl -0.62–-0.16, p < 0.001), and 24 months (WMD -0.48, 95% Cl -0.77–-0.19, p < 0.001). The incidence of pyrexia (RR 1.43, 95% Cl 1.12–1.70, p < 0.001), fatigue (RR 1.26. 95% Cl 1.11–1.43, p < 0.001), and anemia (RR 1.33. 95% Cl 1.14–1.55, p < 0.001) was higher in the zoledronate group than the placebo group for the pooled results from five to six studies.

Zoledronate was more effective in preventing SREs and bone pain than a placebo for up to 24 months in patients with metastatic bone disease. Adverse effects were a class effect related to bisphosphonates; thus, they were not specific to zoledronate. Renal effects, which are associated with this classification of drugs, were not found to be a significant adverse event among patients in these studies receiving 4 mg zoledronate in a 15-minute infusion.

A limitation was that 50% of the studies (n = 6) included in the meta-analysis received a low quality score of 2 or less. However, the authors did report that a sensitivity analysis of the pooled results was unchanged with the removal of these studies’ data from the analysis.

Nurses need to be knowledgeable about the potential adverse effects of zoledronate (more common: pyrexia, fatigue, and anemia; less common: nausea and emesis), which are the same adverse effects of other bisphosphonates. In addition, to prevent renal toxicity, the dose should not be more than 4 mg and should be delivered IV in a 100 ml solution over 15 minutes. Lastly, nurses should be aware that patients can safely receive this drug every three weeks over a period of 24 months with continued pain relief and prevention of SREs.