RESOURCE TYPE: Expert opinion

PHASE OF CARE: Active antitumor treatment

Expert opinion level information

Nurses need to be aware of potential immune-related adverse events and current recommendations for management. Although some differences in opinion exist, overall management involves the use of systemic steroids for moderate symptoms, aggressive use of IV steroids for more severe symptoms, and consideration of immunosuppression for persistent or worsening severe symptoms.

STUDY PURPOSE: To review the evidence for effects of neurolysis for abdominal cancer pain

TYPE OF STUDY:  Meta-analysis and systematic review

DATABASES USED: MEDLINE, EMBASE, AMED, Web of Science, CINAHL from 1980–2011

KEYWORDS: Broad neurolysis terms were used. Terms included pain, quality of life, and possible side effects.

INCLUSION CRITERIA: All study designs and case reports involving percutaneous and endoscopic ultrasound-guided celiac plexus neurolysis, abdominal pain due to intra-abdominal cancers, and adults; English language

EXCLUSION CRITERIA: Noncancer pain; other neurolysis techniques

TOTAL REFERENCES RETRIEVED = 2,303

EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Critical Appraisal Skills Programme was used to evaluate strength of evidence. For case series, a checklist was developed from the Joanna Briggs Institute.

• FINAL NUMBER STUDIES INCLUDED = 66 publications—32 case series, 24 case reports, one survey, and nine RCTs. Five studies were included in meta-analysis that compared celiac plexus neurolysis (CPN) with analgesic therapy.
• TOTAL PATIENTS INCLUDED IN REVIEW = 469 patients in RCTs
• SAMPLE RANGE ACROSS STUDIES = 20–100 patients
• KEY SAMPLE CHARACTERISTICS: Most had pancreatic cancer, but additional abdominal cancers were reported in case series and case reports.

• PHASE OF CARE: Late effects and survivorship     
• APPLICATIONS: Palliative care

Meta-analysis showed a mean difference with CPN (versus analgesics) of -0.87 (95% CI -1.47, -0.28, p = .004) in favor of neurolysis after one to two weeks. After four weeks, the mean difference in pain scores was -0.47 (95% CI -0.71, -0.23, p = .0001). At eight weeks, from four studies, the mean difference with CPN was -0.46 (95% CI -0.68, -0.25, p < .0001). In the two studies that evaluated pain after three months, neither showed a benefit of CPN at that time point.  For endoscopic ultrasound-guided CPN, mean difference at one to two weeks was -4.26 (95% CI -5.53, -3.0, p < .00001), at four weeks was -4.21 (95% CI -5.29, -3.13, p < .00001), and at eight weeks was -4.13 (95% CI -4.84, -3.43, p < .00001). At 12 weeks, only 60 patients could be evaluated. These results in meta-analysis showed a mean difference of -4.28 (95% CI -5.63, -2.94, p < .00001). Analysis also showed significant reduction in opioid consumption from one to four weeks. Meta-analysis of data related to side effects showed higher risk of diarrhea with CPN (p + .0003) and risk of constipation with opioids (RR = 0.34, p < .00001). More nausea and vomiting occured in patients on analgesics (RR = 0.44, p < .0001). Information on side effects, mainly from case series, is provided. Hypotension was shown in four studies to be more prevalent with CPN (RR = 7.43, p = .0003). Across three studies, opioid consumption was reduced with CPN (mean difference = -70.02, p < .0001).

Evidence suggests that CPN reduces abdominal cancer-related pain and that it is a relatively safe procedure. Diarrhea and hypotension are more prevalent with CPN, and constipation is more prevalent with analgesics alone. Analysis was only possible up to two to three months after the procedure, so longer-term efficacy is unknown. It is noted that a significant number of patients with advanced abdominal cancers do not have a long survival time, so this duration is likely clinically meaningful. More evidence is needed to evaluate differences between endoscopic ultrasound-guided and percutaneous CPN.

• There was significant heterogeneity among studies. 
• Methodologic quality of studies was sometimes low, and specific quality data are not reported in the analysis.
• The number of trials included in meta-analyses was low.
• Authors point out a lack of differentiation between somatic and visceral pain, and peritoneal involvement with advanced malignancies can confuse findings because related pain is not transmitted via the celiac plexus.

CPN is shown to be effective for reduction of pain from advanced abdominal cancers, with relatively few side effects. Current evidence, however, only shows duration of effects over about two to three months, so any longer-term efficacy is not known. This procedure may reduce opioid needs, reducing opioid-related complications such as constipation. Nurses should be aware that, although of low prevalence, CPN can be associated with severe complications, so patients need to be observed for these. It needs to be recognized that CPN only can be effective for pain that originates in areas innervated by the celiac plexus.

To investigate the efficacy and tolerability of oxycodone for oxaliplatin-induced peripheral neuropathy (OIPN) with FOLOFOX therapy in patients with colorectal cancer (CRC)

This was a single-center retrospective study of 64 patients with CRC receiving FOLFOX therapy. Controlled-release (CR) oxycodone was concomitantly administered to 29 patients (OXY group). An additional 35 patients (non-OXY group) were not given oxycodone during FOLFOX therapy. The incidence and severity of OIPN and the number of FOLFOX treatments were measured and compared.

• N = 64  
• MEAN AGE = 64.9 years (non-OXY); 62.7 years (OXY)
• MALES: 54.2% (non-OXY); 55.2% (OXY), FEMALES: 48.6% (non-OXY); 44.8% (OXY)
• KEY DISEASE CHARACTERISTICS: Advanced-stage disease (III or IV); all received a gross dissection of primary CRC and subsequently received curative-intent FOLFOX therapy; all were greater than 18 years of age; World Health Organization performance status of 0 or 1; life expectancy greater than six months; none could have preexisting peripheral neuropathy or exposure to previous neurotoxic chemotherapeutic agents
• OTHER KEY SAMPLE CHARACTERISTICS: All patients received standard FOLFOX therapy (bolus of 85 mg/m2 oxaliplatin, leucovorin, and 400 mg/m² 5-FU followed by a 48-hour continuous infusion of 5-FU at 2,500 mg/m² given every two weeks). Bevacizumab, cetuximab, or panitumumab was administered prior to mFOLFOX6 in 27 cases. FOLFOX was continued until disease progression, a decision to use alternative therapies was made, unacceptable toxicities occurred, or a patient refused additional treatment.

• SITE: Single-site    
• SETTING TYPE: Outpatient    
• LOCATION: Toho University Sakura Medical Center in Sakura, Japan

• PHASE OF CARE: Active antitumor treatment
• APPLICATIONS: Elder care, palliative care 

Patients in the OXY and non-OXY groups were evaluated for neurotoxicity. Severity of pain, sensory status, and motor dysfunction were evaluated.

The National Cancer Institute's (NCI's) Common Terminology Criteria for Adverse Events (CTCAE) was used to evaluated neurologic toxicity. A peripheral sensory neuropathy subscale was used to grade clinical severity. Grade 1 could be asymptomatic or could include a loss of deep tendon reflex or paresthesia (including tingling) that did not interfere with function; grade 2 included sensory alterations or paresthesia (including tingling) that interfered with function but not with activities of daily living (ADL); and grade 3 included sensory alterations or paresthesia that interfered with ADL. Pain intensity was measured on a numeric scale after each cycle of FOLFOX therapy.

All patients in the OXY group and 33 out of 35 patients in the non-OXY group experienced grades 1 or 2 sensory neuropathy. Grade 3 neurotoxicity was not observed in the OXY group whereas two patients (5.7%) in the non-OXY group reported grade 3 sensory neuropathy. In the OXY group, sensory neuropathy grades improved in all patients. CR oxycodone was discontinued in 10 patients (34.5%) in the OXY group after completions of FOLFOX therapy. No discontinuations because of OIPN occurred in the OXY group, and 10 discontinuations occurred in the non-OXY group. Patients in the OXY group received a median of 13 cycles. Those in non-OXY group received a median of seven cycles. The median total oxaliplatin dose was higher in OXY group than the non-OXY group (1072.3 mg/m² versus 483 mg/m², respectively).

CR oxycodone may attenuate OIPN and extend FOLFOX therapy in patients with CRC.

• Small sample (< 100)
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment)
• Risk of bias (no appropriate attentional control condition)
• Selective outcomes reporting
• Measurement validity/reliability questionable
• Design observations and retrospective: Pain intensity in 23 patients (79.3%) in the OXY group remained mild throughout the entire study period with no significant change. No quantitative data regarding pain severity were provided. The CTCAE is not a sensitive measure of neuropathy, and it was completed by the provider rather than the patient. Neuropathy symptoms may have been masked by oxycodone.

Additional research on oxycodone and other opioid use for OIPN is needed. This study suggests changes caused by oxycodone, but it has several limitations.

Databases searched were MEDLINE, Cochrane Database of Abstracts of Reviews and Effects, Cochrane Register of Clinical Trials, hand searching from previous systematic reviews, National Guideline Clearinghouse, National Quality Measures Clearinghouse, and Web sites of professional organizations.

Search keywords were extensive and provided in an appendix. 

A panel of nine experts reviewed evidence to identify minimum standards of care. 

This report was part of the RAND Cancer Quality Assessing Symptoms Side Effects and Indicators of Supportive Treatment Project to develop evidence-based tools to evaluate aspects of supportive cancer care practice. The work was supported by a grant from Amgen to RAND.

• Assess for nausea and vomiting at each outpatient visit and within 24 hours of an inpatient visit.
• Evaluate emetogenic risk of every chemotherapy regimen for prevention.
• For highly emetogenic chemotherapy (HEC) and patients with breast cancer on anthracycline with aprepitant, use a three-drug regimen for acute and a two-drug regimen for delayed chemotherapy-induced nausea and vomiting (CINV) prevention.
• For MEC, use 5-HT₃ receptor antagonists and dexamethasone for acute and one of these for delayed CINV prevention.
• For low emetogenic chemotherapy (LEC), use dexamethasone if clinically appropriate.
• Consider electroacupuncture if the technique is available by a capable operator.
• Present alternative treatment options to patients with persistent symptoms within one month in an outpatient setting and within 48 hours in an inpatient setting.

• Minor differences are recommended here in the area of low emetogenic potential compared to some other guidelines, as prophylaxis is suggested here.
• Use of a one-month cutoff for presenting alternatives to people with persistent nausea and vomiting seems like a long time to wait for better symptom control.
• As noted, many pharmacologic options for antiemesis are available; however, in trials, often substantial proportions of patients still do not achieve symptom control. This points to the continuing need for research in this area, as well as individualization of regimens in clinical practice.
• The authors suggest that results of a 2005 systematic review of the effects and costs of 5-HT₃ receptor antagonists for delayed nausea cast doubt on the cost-effectiveness of this approach.

• To assess the analgesic efficacy of prolonged-release (PR) oxycodone in combination with orally administered naloxone PR in patients with severe, chronic pain; to evaluate the efficacy of that combination in improving bowel function
• To evaluate the optimal dose ratio of oxycodone PR to naloxone PR
• To evaluate patients’ and investigators’ treatment preference

In this three-phase study, patients with inadequate pain control entered the titration period, with stabilization at 40, 60, or 80 mg oxycodone PR/day. Those on stable oxycodone dosing who used laxatives to have three bowel movements per week were entered in the maintenance phase after a seven-day run-in period. After patients were stabilized, they were randomized into three naloxone treatment groups or a placebo group. Oxycodone was given open label; naloxone was given in double-blind fashion. After a patient was in the maintenance phase, no titration of oxycodone PR doses was allowed. Those using laxatives were advised to stop unless no bowel movement had occurred for three days. Patients were studied for four weeks, then assessed in a two-week follow-up phase. In the follow-up phase, no one received naloxone PR.

• The intent-to-treat (ITT) group, defined as those who were randomized and received at least one dose of naloxone or placebo and had at least one efficacy assessment, comprised 196 patients; 166 patients completed the study.
• Patients were older than 18 years.
• The sample was 62.9% female and 37.1% male.
• Specific cancer type was not reported.

• Multisite
• Outpatient
• Twenty-eight centers in Germany, May 2002 to April 2003

Prospective randomized double-blind, parallel-group, phase II trial

• Rating scale (1 = very good, 7 = very poor), to measure efficacy and tolerability, used independently by investigators and patients
• Preference, in regard to tolerability and efficacy, for maintenance phase or titration–run-in phase (1 = titration–run-in, 2 = maintenance, 3 = no preference)

• The efficacy of the 2:1 dose ratio of oxycodone PR to naloxone PR was ranked as good or very good by 70.4% of patients and investigators.
• The tolerability of the 2:1 dose ratio was ranked as good or very good by 81.5% of patients and investigators.
• The majority of patients in the treatment arm preferred the maintenance phase, in which they received both medications.
• Naloxone PR had no impact on the analgesic efficacy of oxycodone PR; naloxone PR improved bowel function and reduced laxative intake.

Concurrent administration of oxycodone PR and naloxone PR is effective for the treatment of patients with severe chronic pain, cancer-related or not. Patients tolerated naloxone PR well; naloxone created no  additional untoward effects.

• Exclusion of patients with severe cardiovascular or pulmonary issues limits the applicability of findings to patients with advanced cancers and those taking more than five medications per week to control breakthrough pain.
• Oxycodone PR dosing was limited to 40–80 mg/day.

This study's results relate to pain control and bowel function of patients with cancer. Additional research, to investigate widening application of the findings, is warranted.

To examine the effect of a single dose of palonosetron for the prevention of chemotherapy-induced nausea and vomiting (CINV) in children 18 years of age and younger with acute lymphoblastic leukemia (ALL) treated with high-dose methotrexate (HD MTX) (5 g/m²)

This study was a prospective analysis of the effectiveness of palonosetron given as a single dose (5 mcg/kg) prior to the administration of HD MTX in children 18 years or younger with ALL. Both MTX-naïve patients and previously treated patients were included.  Data was collected on 138 courses of chemotherapy with a total of 53 patients.  Response was determined by patient/parent questionnaires and patient records. Authors described the questionnaires as reporting the occurrence of emesis, the intensity of nausea, and the use of rescue therapy at six-hour intervals from day 1 until discharge. Intensity of nausea was measured using a visual analogue score (VAS) ranging from 0 to 10. Complete response was defined as no emetic episodes and no use of rescue medications during the acute phase (0–24 hours) and the delayed phase (24–66 hours).

• This study reported on 53 patients.
• Ages ranged from 2–18 years.
• The sample was 60% male and 40% female.
• All patients had been diagnosed with ALL and were receiving 5 g/m² HD MTX.

This was a multi-site study conducted in Denmark.

• Patients were in active antitumor treatment.
• This study has application for pediatrics.

This was a prospective trial.

• The questionnaire was not specifically identified, and no reliability data was provided.
• A 0–10 VAS was used to measure nausea intensity.

• Complete response (i.e., no emesis and no rescue therapy) was achieved in 84.1% of courses during the acute phase and 60.1% of courses during the delayed phase.
• During the acute phase, 92% of courses were completely free of emesis. During the delayed phase, 86.2% were free of emesis.
• During the acute phase 89.9% of patients did not receive any rescue therapy, compared to 65.2% during the delayed phase.
• Additionally, 76.8% of courses were free of nausea during the acute phase, and 78.3% of courses were free of nausea during the delayed phase.

This study demonstrated that a single dose of palonosetron was effective in the prevention of CINV in children 18 years old and younger with ALL receiving HD MTX both in the acute and delayed phases.

• The sample size was small with fewer than 100 patients.
• A risk of bias exists because no control group or random assignment was included. The sample characteristics also introduce a risk of bias.
• The measurements and methods were not well described and the validity and reliability of the tools was questionable.
• No data regarding the expected frequency of nausea or vomiting in this population or regimen was included.
• Some patients also received intrathecal (IT) MTX and anesthesia prior to receiving HD MTX, which could have impacted results.
• The investigators used multiple cycles from the same patients, which could introduce bias if patients had a history of CINV.

Palonosetron has been effective for moderate to highly emetogenic chemotherapy in acute and delayed CINV in adults. This study demonstrated that a single dose of palonosetron was effective in preventing both acute and delayed phase CINV in the majority of children under age 18 with ALL receiving HD MTX.  Prospective randomized controlled trials should be conducted in other pediatric oncology populations to determine generalizability of these findings.

To perform a systematic review of evidence of the efficacy and toxicity of nonsteroidal antiinflammatory drugs (NSAIDs) or paracetamol in addition to World Health Organization (WHO) step III opioid treatment for moderate to severe cancer pain in comparison to opioids alone

The type of study is systematic review.

Databases searched were MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials.
Search keywords were acetaminophen, paracetamol, neoplasm, pain, and NSAID.
Studies were included in the review if they were

• Written in English
• Had a publication date of 2002–2010
• Conducted with adult human participants experiencing chronic cancer pain
• A randomized controlled trial or a meta-analysis reporting on efficacy and/or side effects of NSAIDs or paracetamol in addition to opioids in comparison to opioids alone.

No specific exclusion criteria was identified.

A total of 803 references were retrieved. 

After further review by the authors, 12 studies were included in the literature review.

Each study was evaluated in terms of content and quality using the Cochrane Handbook for Systematic Reviews of Interventions as the tool for appraisal.

• A final number of 12 studies were included in the review.
• The total number of patient cases included in the review was 396.
• The article does not describe patient demographics or characteristics, including cancer diagnoses.

• Patients were undergoing multiple phases of care.
• The study has clinical applicability for palliative care.

Adjuvant use of NSAIDs has been demonstrated to provide an additive effect in either improving pain management or reducing opioid use. Paracetamol use did not demonstrate any significant improvement over opioid use alone.

The articles reviewed provide weak support of the addition of NSAIDs to WHO step III opioids to improve analgesia and/or reduce opioid dose amount. The addition of paracetamol in combination with step III opioids cannot be supported by the current research review.

Several limitations were identified during the process of systematic review, including small sample, large losses to follow-up, no intention-to-treat analysis completed, short follow-up (one to five days), and evidence of sponsorship by industries (bias).

This review adds to the body of evidence that routine use of acetaminophen to opioids for chronic pain management is not effective for pain reduction or reduction in opioid dosage needed for pain control. Acetaminophen does have potential negative effects with long-term or high-dose use, so this approach should not be implemented as a routine. A growing body of research is challenging the WHO ladder approach to pain management.

To determine the overall efficacy of psychological interventions, in patients with breast cancer, in regard to the outcome variables of anxiety, depression, and quality of life; to examine the moderating effects of disease stage, treatment type, duration, and orientation on overall treatment efficacy

Databases searched were MEDLINE (1966–January 2004), EMBASE (1980–2004), Cochrane Controlled Trials Register (1985–February 2004), PsycLIT (1973–2004), Biological Abstracts (1990–December 2003), CANCERLIT (1975–October 2002), CINAHL (1982–December 2003), and Health Start (1975–January 2004).

Search keywords were cognitive behavioral therapy, group psychotherapy, relaxation, supportive therapy, visual imagery, anxiety, depression, maladjustment, distress, and quality of life. Authors included no language or publication-status restrictions.

Studies were included if they met all these criteria:

• Were randomized controlled trials (RCTs) that evaluated the efficacy of a psychological or behavioral intervention and were aimed at alleviating psychiatric or psychological morbidity
• Included women participants who had
  • A histologically confirmed diagnosis of breast carcinoma of any stage
  • Undergone surgery
• Included at least two arms: an intervention and a control

Studies examining the efficacy of interventions to assuage surgical distress were ineligible.

• Investigators initially reviewed a total of 36 studies.
• The final number of studies assessed for the analysis was 18: 14 studies assessed anxiety and 14 assessed depression.
• Two reviewers assessed eligible trials and assigned a methodological grade by using the Jadad scale. Trials were pooled under outcome variables (anxiety, depression, and quality of life) to obtain three overall effect sizes, with negative values suggesting a favorable outcome for the treatment condition.
• Also included was an academic textbook, Psychosocial Interventions for Cancer, by Baum and Anderson (2001).
• Eight studies were carried out in facilities in the United States; four, in Canada; one, in England; two, in Australia; and one each in Japan, Italy, and China.
• Eight studies had a score of 5 or greater on the Jadad scale. Ten had a score of less than 5.  The maximum score earned by an assessed study was 7.

• Sample range across studies:
  • Anxiety: 1,278 participants, 692 in treatment group and 586 in control.
  • Depression: 1,324 participants, 713 in treatment group and 611 in control.
• Participant age range was 25–73 years.
• Of participants, 70% were married or in a committed relationship, 32% were Caucasian, 23.7% were Asian, 10.2% were African American, and 28.4% were Hispanic. The race of 28.4% was unidentified.

Depression: Authors reported a clinically moderate-to-strong effect (–1.01, 95% CI –1.48 to –0.54, N = 1,324) and robust finding (95% Cl –0.69 to –0.24) in studies treating patients with high psychological morbidity and methodologically more reliable studies. Short-term interventions compared to long-term interventions (–0.56 versus –0.40) showed a stronger clinical benefit for metastatic patients. Group interventions appeared to be moderately to strongly effective in treating depression in advanced disease (–0.56), compared to early-stage disease (–0.15). Cognitive behavioral interventions (–0.56) may be more effective than supportive expressive therapies (–0.36) for patients with advanced disease.

Anxiety: Most trials were conducted on a prophylactic basis rather than involving highly anxious patients. Findings suggested that a moderate-to-strong clinical impact may be observed in patients with breast cancer who are experiencing clinically significant anxiety. Short-term interventions were associated with clinically moderate effects; longer-term interventions also showed a clinically moderate effect (–0.40) in favor of treatment for patients with metastatic disease but not for those with early-stage breast cancer. Group interventions demonstrated a clinically moderate impact in favor of treatment (–0.40). Patients with more-advanced disease made clinically moderate gains (–0.36) with cognitive behavioral interventions, comparable to the gains made with expressive-supportive therapy (–0.40). Relaxation and guided imagery studies were of lower methodological grade; pure educational interventions failed to show any clinical benefit.

The process of attempting to pool trials and explore effects is complicated and often misleading. Key findings follow.

• In general, interventions targeting patients with clinically diagnosable levels of anxiety or depression are more beneficial than are interventions targeting patients with a lower level of anxiety or depression.
• Group psychotherapy appears to be more effective than individual therapy at treating both anxiety and depression.
• Within a group format, cognitive behavioral interventions appear to be equally effective as supportive-experiential therapies. Duration of treatment need not exceed 20 hours.

Most trials in this analysis relied solely on self-reported measures of anxiety and depression. Literature in the field of cancer indicates that patients with cancer may under-report these symptoms; therefore, self-reported measures may be unreliable and collateral data are needed. In addition, further investigation of the timing of psychological intervention, to determine when the intervention is best delivered, is needed.

To determine the overall efficacy and magnitude of clinical benefit of psychological interventions in patients with breast cancer, specifically looking at three outcome variables: anxiety, depression, and quality of life (QOL)

Databases searched were MEDLINE (1966–January 2004), EMBASE (1980–2004), Cochrane Controlled Trials Register (1985–February 2004), PsycLit (1973–2004), Biological Abstracts (1990–December 2003), CancerLit (1975–October 2002), CINAHL (1982–December 2003), and Health Star (1975–January 2004).

Search keywords were randomized clinical trial and breast cancer and psychological interventions (cognitive behavioral therapy, group psychotherapy, relaxation, supportive therapy, visual imagery) and psychological adjustment (anxiety, depression, maladjustment, distress, quality of life).

Studies were included in the review if they

• Were a randomized clinical trial (RCT)
• Included at least two arms: an intervention arm and a control arm
• Evaluated the efficacy of a psychological/behavioral intervention
• Were aimed at alleviating psychiatric/psychological morbidity, as defined by anxiety, depression, and/or QOL
• Reported on female patients with a histologically confirmed diagnosis of breast carcinoma of any stage who have undergone surgery.

Trials examining efficacy of interventions designed to assuage surgical distress were excluded.

• A total of 383 citations were identified, with 36 potentially relevant articles identified and screened for retrieval.
• The final meta-analysis included 18 RCTs with usable information by outcome.
• Study quality was evaluated using a framework provided by Cook and Campbell (1979) and a quality assessment scale developed and validated by Jadad and colleagues (1996).

Cook, T.D., & Campbell, D.T. (1979). Quasi-experimentation: Design and analysis issues for field settings. Boston, MA: Houghton Mifflin.

• Fourteen trials assessing anxiety were identified, yielding a sample of 1,278 patients.
• Fourteen trials measuring depression were identified, yielding a sample of 1,324 patients.
• Seven trials measuring QOL were identified, yielding a sample of 623 patients.
• Less than half of the trials included were considered to be of high methodological quality.
• Patients’ ages ranged from 25 to 73 years, and approximately 70% were married or in a committed relationship.
• Studies were conducted in the United States, Canada, England, Italy, Australia, Japan, and China.

Anxiety

• Overall effect size (ES) was -0.40 (95% CI, -0.72 to -0.08) in favor of the treatment condition in comparison to the control.
• Sensitivity analyses exploring the impact of methodological quality on overall ES found a reduction in ES associated with higher quality studies, -0.26 (95% CI, -0.42 to -0.10).
• Trials using patients with high morbidity (metastatic breast cancer) yielded a statistically significant overall ES of -0.40.
• Trials whose treatment extended beyond 20 hours had a statistically significant overall ES of -0.30 in favor of treatment.
• Treatment orientation showed differential impact on overall ES with cognitive behavioral therapy (CBT), yielding an ES of -0.11, as well as ESs of -0.40 for guided imagery and relaxation, -0.43 for supportive-expressive therapy, and 0.02 for educational interventions.

Depression

• Overall ES for depression was -1.01 (95% CI, -1.48 to -0.54) in favor of treatment.
• Trials with higher methodological grade were associated with an overall ES of -0.24 in favor of treatment, while lower quality studies had an overall ES of -1.99.
• Studies in which patients had lower morbidity yielded an overall ES of -0.45, whereas those with patients with more advanced disease yielded an overall ES of -1.20.
• Couples and group therapy reached statistical significance with an ES of -1.02 and -1.35, respectively.
• Treatment orientation showed ESs of -0.85 for CBT, -0.55 for guided imagery, -1.80 for supportive expressive therapy, and -0.45 for educational interventions. With the exception of educational interventions, the other subgroup analyses reached statistical significance.

Quality of Life

• Overall ES was 0.74 (95% CI, 0.12 to -1.37) in favor of the treatment group, but this was not statistically significant. When lower quality studies were removed, statistical significance was achieved, but ES was reduced (0.35, p=0.04).

Overall ES trends among the three outcomes show that more reliable studies were associated with smaller gains. Interventions targeted to patients with clinically important levels of anxiety or depression tended to reap the most benefit, compared to patients who undergo treatment on a prophylactic basis. Group psychotherapy appears to be superior to individual therapy in the treatment of both anxiety and depression. However, a direct impact of group therapy on QOL was not supported in this analysis. CBT interventions appeared to be equally as effective as supportive-experiential therapies. Interventions need not span beyond 20 hours to produce statistically significant ES.

The quality of most studies was not high.

Future trials in psychosocial oncology should incorporate methodological features to enhance internal validity. Evaluation of statistically significant findings on psychometric testing may not reflect clinically significant findings and vice versa. This underscores the need for incorporating qualitative analysis in future studies. There is an absence of studies examining the efficacy of short-term interventions on QOL in advanced breast cancer and should be addressed in future research. Short-term, group interventions may provide the best utilization of scarce resources for the most effect; however, they should be targeted to those patients experiencing clinically important levels of distress. Findings point to the need for higher quality research design and reporting in this field.

To evaluate the efficacy of nefopam on acute and chronic postoperative pain from breast surgery

Women were randomized to either nefopam or normal saline placebo control. All patients received 0.05mg/kg of midazolam preoperatively, and all patients received the same anesthetic regimen. At the end of surgery, 30 mg of IV ketorolac was given and, postoperatively, patients were given 0.5 mcg fentanyl if pain rating was 5 or higher. After discharge from PACU, ketorolac was given according to pain ratings, and meloxicam daily was begun as soon as patients started eating. Pain was assessed at 6 and 24 hours postop and at 10 days and at three months.

• N = 83   
• MEAN AGE = 53.2 years
• FEMALES: 100%
• CURRENT TREATMENT: Other
• KEY DISEASE CHARACTERISTICS: All had breast cancer.
• OTHER KEY SAMPLE CHARACTERISTICS: All were scheduled to undergo lumpectomy.

• SITE: Single site   
• SETTING TYPE: Multiple settings    
• LOCATION: Republic of Korea

• PHASE OF CARE: Active antitumor treatment

• Double-blind, randomized, controlled trial

• Numeric rating scale for pain

Pain scores were significantly lower in the nefopam group immediately after surgery, and at 6 and 24 hours postoperatively (p < 0.01). No differences existed in pain rating at 10 days and three months. Analgesic consumption during the initial postoperative period was also lower in the nefopam group (p = 0.03). Some differences in pain were seen between groups when stratified according to postoperative radiation or nonradiation.

Prophylactic use of nefopam was associated with reduced pain in the first three days postoperatively among women undergoing surgery for breast cancer.

• Small sample (< 100)

Nefopam is a strong central-acting nonopioid analgesic that was shown to be of benefit for management of acute pain. This medication is more commonly used in European countries, and may be a useful alternative to opioids in patients with cancer. Further research is needed to explore its utility for management of various types of cancer-related pain and comparative effectiveness with other common approaches for pain management.