To assess existing guidelines, related and unrelated to cancer, as a means of developing evidence-based, consensual recommendations regarding the management of cancer-related pain in adults and children with cancer

• Investigators retrieved 25 guidelines for review. Two or three panel members, working independently, scored each set of guidelines by using the Appraisal of Guidelines for Research and Evaluation (AGREE) Instrument to assess quality. Panel members evaluated the domains included in each set of guidelines, including target audience of healthcare providers, environment for which the guideline was written, and the population for whom it was written. Based on quality and domains, eight guidelines were selected as sources from which to extract information to use to develop recommendations.
• The database searched was MEDLINE, using the OVID system, 2000–May 2006. In addition, investigators searched the Internet to retrieve unpublished guidelines from Canadian and non-Canadian health organizations. The National Guidelines Clearinghouse, Guideline International Network, and the McMillan Group were included.
• Search keywords were pain, pain management, neoplasm, pediatric, aged, guideline, and practice guideline.

The reference provides AGREE scores for 11 aspects of pain management across the eight published guidelines as well as detailed recommendations for each of the aspects of pain management.

The authors reviewed these guidelines:

• Scottish Intercollegiate Guidelines Network (SIGN): Control of Pain in Patients With Cancer
• The American Geriatrics Society (AGS): The Management of Persistent Pain in Older Persons
• Registered Nurse Association of Ontario (RNAO): Assessment and Management of Pain
• National Breast Cancer Center and National Cancer Control Initiative (NBCC-NCCI), Australia: Clinical Practice Guidelines for the Psychosocial Care of Adults With Cancer
• Canadian Association of Nursing Oncology (CANO): Cancer Pain Management Manual
• American Pain Society (APS): Guideline for the Management of Cancer Pain in Adults and Children
• Canadian Pain Society (CPS): Accreditation Pain Standard: Making It Happen
• Cancer Care Nova Scotia (CCNS): Best Practice Guidelines for the Management of Cancer-Related Pain in Adults

The analysis led to the statements and recommendations that follow.

• Assessment of pain:
  • Patient self-reporting is the most reliable indicator of pain.
  • Assessment should include physical, functional, spiritual, and social domains of pain.
  • Assessment tools must be valid and appropriate to the age of the patient and the patient's population.
• Plan of care:
  • Establish a written plan of pain management. The plan should be interdisciplinary and consistent with individual and family goals. The guidelines list factors to be considered in the plan.
  • Patients, family members, and caregivers should receive a copy of the written pain management plan. The plan should include causes of pain; types and reasons for analgesic medications; instructions regarding dosage and titration; the side effects of analgesics; the name of the person to call if pain is not relieved or side effects occur; instructions about when and how to use nonpharmacologic approaches; instructions about filling and renewing prescriptions; and realistic goals, timelines, and expectations about pain control.
  • The plan should be updated upon reassessment.
  • Adherence to the plan and other factors should be reassessed at regular intervals and with each new report of pain.
• Pharmacologic Interventions
  • A key principle is to titrate analgesic dosage to achieve desired pain relief and minimize unwanted side effects. Selecting analgesics should involve consideration of pain intensity, patient age, comorbidities, concurrent drugs, prior treatment outcomes, patient preferences and convenience, and cost. The guidelines outline specific considerations relating to each of these areas.
  • Use the simplest analgesic dosage schedules and least-invasive modalities; however, using other than the oral route may be appropriate to provide immediate relief. The route should be tailored to the pain situation and the care setting.
  • The intramuscular route is not recommended.
  • The guidelines provide specific recommendations about opiod use, management of breakthrough pain, principles regarding dose titration, and use of long-acting opiods when dosages are stable. The guidelines recommend
    • Using the same opiod  for round-the-clock dosing and breakthrough pain.
    • Considering opiod rotation.
• Safety and efficacy:
  • To prevent barriers to pain relief, providers should know the difference between addiction, tolerance and dependency. The guidelines define each condition.
  • Respiratory impairment should not be a reason to avoid opiod use, but patients with respiratory impairment who are using opiods should be closely monitored.
  • Establish a protocol for the use of naloxone to manage opiod-induced respiratory depression.
• Side effects: Clinicians should anticipate side effects and institute prophylactic treatment to avoid them.
• Coanalgesic agents: These agents are important adjuncts for pain control. Anticonvulsants and antidepressants provide analgesia for specific types of pain. These should be used with extra caution when prescribed for the elderly.
• Nonpharmacologic interventions: Combine nonpharmacologic interventions with pharmacologic methods according to individual preferences and goals, including such things as psychosocial and spiritual support services.
• Specialty care: Provide access to specialists in cases involving complex pain problems, such as palliative radiation, pulse chemotherapy, spinal infusion, etc.
• Documentation: Documentation should comprise all components of the assessment, including the plan of care, information about interventions and patient responses, and a summary of all education provided to the patient and family. Documentation should be updated as often as pain is assessed or changes occur.
• Education: Education should be provided to patients, family members, and informal care providers, to clarify myths and misconceptions about tolerance and addiction and to promote involvement in effective pain management.
• Outcome measures: Use outcome measures as part of a formal process to evaluate and improve the quality of pain management across all disease stages and across all settings.

Authors did not identify any conflicts of interest.

This reference, a set of standards of practice, provides extensive and detailed guidance regarding all aspects of pain management. The standards can be a very useful reference through the entire process of pain management for patients with cancer.

Refer to the original document: This summary does not contain the full detail that the guidelines provide. The guidelines discuss opioid dosage determination in detail and recommend nonpharmacologic methods; however, the guidelines do not make specific recommendations about modality.

4,900 references were identified that were published between January 1, 1990 and December 31, 2013. 203 articles were included in the final review although only 174 were referenced. Grades used and reported here were A: recommended, high certainty of benefit, B: recommended, high certainty of moderate to substantial benefit, D: recommends against use, moderate to high certainty of no net benefit, and H: recommends against use, moderate to high certainty that harms outweigh benefits.

Interventions for specific symptoms that had strong recommendations for or against use were:

• Anxiety: Music therapy during RT and chemotherapy sessions, meditation, and yoga for patients undergoing therapy (B-level recommendation)
• Depression: Mindfulness-based stress reduction for patients undergoing radiotherapy, relaxation, and yoga (level A recommendation); massage and music therapy (level B)
• Fatigue: Energy conservation (level B)
• CINV: Acupressure and electroacupuncture in addition to antiemetics (B level)
• Neuropathy: Acetyl L carnitine was not recommended because of harm (H level).
• Radiodermatitis: Aloe vera and hyaluronic acid cream were not recommended as standard therapy because of lack of effect (D level).

It appears that only specific types of interventions were included, and there are numerous types of integrative or complementary interventions that were not considered in this review. The findings considered were limited to women with breast cancer. Quality rating of evidence was not discussed individually.

These guidelines provided an evidence-based evaluation of various integrative therapies in women with breast cancer. This set of interventions is not all-inclusive; however, it does provide some guidance to clinicians and others regarding evidence strength in these areas as assessed by this specific study group.

To investigate electroacupuncture to prevent or reduce chemotherapy-induced peripheral neuropathy (PN) associated with taxanes

Women with breast cancer scheduled to receive 12 weeks of adjuvant or neoadjuvant paclitaxel were recruited. Patients were randomized to receive either 12 weekly electroacupuncture or sham electroacupuncture treatment. These were done within two days of the weekly chemotherapy administration. A standard acupuncture protocol was used. The sham procedure did not include any true acupuncture points, and no electric current was transmitted. Study assessments were conducted at weeks 6, 12, and 16.

• N = 48   
• MEAN AGE = 50.1 years
• AGE RANGE = 27–79
• FEMALES: 100%
• CURRENT TREATMENT: Chemotherapy
• KEY DISEASE CHARACTERISTICS: All had breast cancer and were receiving chemotherapy with taxane; most had paclitaxel only.

• SITE: Single site   
• SETTING TYPE: Outpatient    
• LOCATION: New York

PHASE OF CARE: Active antitumor treatment

Single-blind, sham-controlled, randomized, controlled trial

• Brief Pain Inventory (BPI)
• Functional Assessment of Cancer Therapy (FACT) neurotoxicity (NTX) and taxane (TAX) questionnaires
• Grooved pegboard test
• Biothesiometer testing

In the sham group, 45% completed all sessions, and 59% completed the electroacupuncture sessions. The number of sessions attended ranged from 1–12. There were no differences in pain scores at weeks 6 and 12. At week 16, the worst pain in the sham group returned to baseline but increased in the acupuncture group (p = 0.03). There were no differences between groups in biothesiometer or pegboard test results. At week 16, those receiving actual acupuncture reported higher pain on the FACT questionnaires.

Women who received electroacupuncture reported greater increases in pain over time compared to controls. There were no other differences in neuropathy findings between groups.

• Small sample (< 100)
• Subject withdrawals ≥ 10%
• High variability in adherence to sham and actual treatment sessions

The findings of this study did not support the use of electroacupuncture to prevent or mitigate symptoms of PN in women receiving paclitaxel chemotherapy.

The purpose of the study was to evaluate the efficacy of a single fixed 6 mg dose of pegfilgrastim compared with daily filgrastim.

Patients were randomly assigned to receive either a single fixed dose injection of 6 mg pegfilgrastim on day 2 of their treatment cycle or daily injections of filgrastim 5 mcg/kg per day, begun about 24 hours after chemotherapy until documented absolute neutrophil count (ANC) of 10 x 10⁹/L or greater. Chemotherapy dose reductions were permitted if patients had grade 3-4 non-hemopoetic toxicities.

• 152 total participants were evaluated.
• Mean age of the participants was 52.4 years, with a range of 30–75 years.
• All of the participants were women.
• The disease type was not stated. All were receiving doxorubicin and docetaxel chemotherapy every three weeks.
• Patients were excluded if they received systemic anti-infective treatment within 72 hours of chemotherapy.

• Multi-site
• Outpatient 
• 37 centers in Europe, Australia, and the United States

Active antitumor treatment

Double-blind randomized phase III

• Weekly blood samples for ANC determination
• Grade 4 neutropenia defined as ANC less than 0.5 x 10⁹/L
• Neutrophil recovery defined as ANC of 2.0 x 10⁹/L or greater

In cycle 1, mean duration of neutropenia was 1.8 days with pegfilgrastim and 1.6 days in the filgrastim group—no significant difference.  There were no differences between groups for duration of grade 4 neutropenia during other treatment cycles. The safety profile of pegfilgrastim was similar to that for filgrastim.

A single fixed dose of pegfilgrastim per chemotherapy cycle is as safe and effective as daily filgrastim injections.

No significant study limitations were identified.

This study demonstrated that a single fixed dose of pegfilgrastim was as safe and effective as daily filgrastim in these patients. The ability to provide the same effectiveness with fewer injections can be beneficial to patients.

• Participants were assigned randomly to one of three factor-control groups.
• Patients were given a 10-minute foot massage (five minutes per foot) on three consecutive days from 7–8 pm.
• Patients were given slow and firm massage or gentle strokes toward the heart, from the base of the toes up the foot and lower leg to the knee.
• Patients received a short foot massage before study enrollment to reduce the possibility of anticipatory anxiety.

• The study consisted of 87 participants.
• The sample was 60% female and 40% male.
• Patients ranged in age from 18-88 years.
• To be included, patients had to have
  • Been diagnosed with cancer.
  • Been 18 years or older.
  • Reported pain or nausea.
  • Had not received surgery in the last six weeks.
• Primary cancer sites varied, and 32 participants had metastatic disease.

All participants were in the inpatient setting. No further setting description was provided.

• Patients reported symptoms using a 100-mm visual analog scale (VAS) with 0 mm = no nausea, and 100 mm = vomiting or dry retching.
• Heart rate and subjective data were measured at two intervals: before massage and 10–20 minutes after completion of massage.
• On control nights, participants stayed quietly in bed and did a quiet activity with the same measurements.

Evidence suggested that massage reduces feelings of nausea. No significant difference was found between the control session pretest mean nausea score and post-test mean nausea score. In contrast, the mean nausea scores for the massage sessions decreased.

• In session 1, t = 3.117, p = 0.0012, and the mean difference was 6.4 mm.
• In session 2, t = 3.178, p = 0.0011, and the mean difference was 4.9 mm.

• The study did not control for medications, although they were recorded.
• Findings were not correlated with diagnosis, type of cancer, metastases, or treatment schedules.
• The long-term effects of massage are unknown.
• Pain and relaxation were measured as well as nausea and vomiting.

L-carnitine is essential for glucose and lipid turnover and has a role in maintaining energy metabolism.

A high daily fractionated dose ​L-carnitine 2-g solution was given twice daily (BID) for seven days. Ifosfamide and cisplatin cause increased renal excretion and alter the usual enzyme pathways, potentially causing asthenia with impaired energy metabolism.

The study included 50 nonanemic adults with stage IV solid tumors receiving combination chemotherapy, including ifosfamide or cisplatin, with palliative treatment intent.

Not described

The study used a prospective, nonrandomized, single-arm trial, open-label, pre-/posttest design.

Functional Assessment of Cancer Therapy-Fatigue (FACT-F), 13 items with ratings from zero to four

All 50 patients were evaluable; 20 patients had fatigue at the first cycle and 30 had fatigue at the second cycle. L-carnitine levels were greater than 30 μm in 100% of the patients, and it was well tolerated. Fatigue was ameliorated in 90% (n = 45) with L-carnitine (p < 0.001). Of the nonresponders, three patients were stable and two got worse.

• The study had a small sample size.
• The study used a nonrandomized design.
• No comparison group was included.
• L-carnitine depletion may not be the primary cause of fatigue experienced by these patients.
• L-carnitine could be resupplied through diet, which was not monitored.
• Urinary loss of L-carnitine may be asymptomatic.

Cost of supplements and monitoring levels of L-carnitine is unknown.

To assess the effect of providing systematic full access to the medical record on patients’ anxiety, quality of life, and satisfaction

Participants were randomly assigned to either requested access to the medical record or systematic full access groups. In the requested access group, information and the medical record were delivered to the patient at the physician’s or patient’s request. In the systematic access group, patients were given a briefcase that they were to bring to each visit. The briefcase was filled with administrative data as well as reports of surgery, pathology, laboratory, radiology, and hospitalizations and nursing narrative notes. Documents were provided to the patient as well as on CDs, including radiology images. Documents were updated at each visit, and in between visits materials were mailed to the patient. A coordinator provided updated information for the patient to put in the briefcase and explained the material to the patient in a standardized way. Medical and nursing staff also provided information and answered patient questions. Patients completed questionnaires for the study data collection at the beginning of the study and at the end of their first chemotherapy cycle.

• The study reported on a sample of 295 patients.
• Mean patient age was 54.6 ± 12.1.
• The sample was 86.8% female and 31.2% male.
• Newly diagnosed breast cancer, colon cancer, and Hodgkin and non-Hodgkin lymphoma were the most common diagnoses.
• All patients were beginning adjuvant chemotherapy.
• Of the sample, 70.6% were married or cohabiting, 50.2% had secondary or higher level education, and 61.7% were currently employed.

• Multisite
• Outpatient setting
• Cancer center in France

Patients were undergoing the active treatment phase of care.

The study was a randomized controlled trial with repeated measures.

• Spielberger State-Trait Anxiety Inventory
• European Organization for Research and Treatment of Cancer Quality of Life Questionnaire
• Four-point Likert-type scale for satisfaction

Mean anxiety score at baseline was 40.7 in all patients (scores of 20–80 generally indicate a higher level of anxiety). There were no differences at baseline between groups and no change over time in the systematic full access group. There was a significant reduction in anxiety at the end of treatment in the requested access group (p = 0.009), but no differences between study groups. There were no differences between groups in quality-of-life findings. A higher percentage of patients in the full access group were completely satisfied with treatment explanations than in the requested access group; however, the difference between groups was not significant. Full access was not a source of anxiety for 68.8% of patients, and 82.2% said they understood the information.

Provision of full information in an organized medical record provided to patients did not increase patient anxiety, was practical to implement, and may have a positive effect on patient satisfaction with information.

• There was no subgroup analysis of state anxiety findings by anxiety trait findings. 
• The satisfaction measure was a single measure with no established validity or reliability.

This study outlines a practical way to provide full medical record information to patients in a way that was acceptable to them. Findings show that provision of full information did not increase patient anxiety and was associated with a tendency for patients to have more satisfaction with information provision. This may be a useful approach to engage patients in their care. Most of these patients were fairly well-educated, so it is not clear whether these results can be generalized to less educated patients.

To review the effectiveness and safety outcomes of patients selected to receive surgical procedure for lymphedema (LE) after a program of complete decongestive therapy (CDT)

LE therapy consisted of manual lymph drainage, compression bandaging and garments, and vascularized lymph node transfer (VLNT), which was used for upper extremity LE by removing lymph nodes from the groin and transferring them to the affected axilla or along with a deep inferior epigastric perforator (DIEP) flap. Lymphaticovenous anastomosis (LVA) was preferred for lower extremity LE, which was completed by connecting lymphatics to nearby microscopic veins. Both VLNT and LVA are for LE with primarily fluid component. Suction-assisted protein lipectomy (SAPL) is used to treat the solid type of LE and requires continued compression after procedure.

• N = 26
• MEAN AGE = 53 years
• FEMALES: 100%
• KEY DISEASE CHARACTERISTICS: Women with upper extremity LE secondary to breast cancer, congenital lower extremity LE, or lower extremity LE secondary to gynecologic cancer treatment

• SITE: Single-site    
• SETTING TYPE: Inpatient    
• LOCATION: University of California, Los Angeles, United States

• PHASE OF CARE: Transition phase after active treatment
• APPLICATIONS: Elder care, palliative care

Retrospective chart review

• Circumferential limb volume
• Excel database
• Paired T-tests for pre-/postoperative comparisons
• Volume reduction for SAPL at 4 and 12 months after surgery
• Change in compression garment use and lymphedema therapy necessary for VLNT and LVA
• Change in the incidence of cellulitis in all cases

The retrospective chart review of 26 selected patients from one surgeon identifying phases of LE, earlier with fluid component swelling, using VLNT, LVA, or SAPL showed positive results in regard to volume reduction, decreased infection episodes, and decreased garment/CDT requirements.

• Small sample (< 30)
• Baseline sample/group differences of import
• Risk of bias (no control group)
• Selective outcomes reporting
• Key sample group differences that could influence results
• Intervention expensive, impractical, or training needs

Carnitine is a cofactor required for cell energy production that serves as the primary fuel source for heart and skeletal muscles. Cancer-related anorexia/cachexia syndrome (CACS) and oxidative stress (OS) are two prominent features in patients with advanced cancer; therefore, L-carnitine supplementation was tested in patients with advanced cancer. Based on the current knowledge of carnitine use, patients took three doses (2 g) of L-carnitine orally each day for four weeks. Patient outcomes were evaluated at baseline (T0), week two (T1), and week four (T2).

• Twelve patients with locally advanced or metastatic disease were included.
• Mean age was 60 years (range 42–73).
• The majority of patients were women (n = 10) with mixed tumor sites (most common being gynecological cancer), and most were receiving concomitant chemotherapy (n = 10). 
• Patients were excluded if they had an Eastern Cooperative Oncology Group (ECOG) performance status of greater than 2, had insulin-dependent diabetes mellitus, or were pregnant.

Patients were undergoing the active treatment phase of care.

The study was an open-label, nonrandomized trial. 

Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF)

The L-carnitine intervention resulted in improved fatigue outcomes. The observed decline in MFSI-SF fatigue scores was statistically significance at both T1 (p < 0.05) and T2 (p < 0.001) in comparison to the baseline scores. Mean MFSI-SF scores at T0, T1, and T2 were 25.40 (standard deviation [SD] = 13.91), 16.93 (SD = 11.92), and 12.05 (SD = 12.56), respectively. Evaluation of subscales showed a statistically significant difference from T0 to T1 for the General subscale (p < 0.05) and the Physical subscale (p < 0.05).

• The study had a small sample size. 
• The study lacked a neutral comparison group.

To assess the safety and evaluate the efficacy of ​a fixed-dose combination of netupitant and palonosetron (NEPA) over multiple cycles of highly emetogenic chemotherapy (HEC) and moderately emetogenic chemotherapy (MEC)

Oral NEPA (​netupitant [NETU] 300 mg + palonosetron [PALO] 0.50 mg) + dexamethasone (DEX) versus oral aprepitant (APR) (125 mg Day 1; 80 mg Days 2–3) + oral PALO 0.50 mg Day 1 + DEX (for HEC, DEX Days 1–4; for MEC, DEX Day 1 only)

• N = 412  
• AVERAGE AGE = 58 years 
• MALES: 50%, FEMALES: 50%
• KEY DISEASE CHARACTERISTICS: Eligible patients were ≥ 18 years, diagnosed with a malignant tumor, naïve to chemotherapy, and scheduled to receive repeated, consecutive courses of chemotherapy (HEC/MEC). A single intravenous (IV) dose of one or more of the intervention versus control agents was administered on Day 1. Single-day chemotherapy was necessary for inclusion. ECOG ≤ 2.
• OTHER KEY SAMPLE CHARACTERISTICS: Non-AC chemotherapy, no previous NK1RA use, no CYP3A4 inducer use within four weeks, no bone marrow transplant or stem cell rescue therapy, no known hypersensitivity of or contradiction to 5-HT3RA or dexamethasone.

• SITE: Multi-site    
• SETTING TYPE: Outpatient    
• LOCATION: Multinational including Bulgaria, Czech Republic, Germany, Hungary, India, Poland, Russia, Serbia, Ukraine, and the United States

• PHASE OF CARE: Active antitumor treatment

Phase 3 multinational, double-blind, double-dummy, parallel group study design

• Safety: Treatment-emergent adverse events (TEAEs), labs, physical exams, vital signs, ECGs, cardiac troponin I (cTnl), and left ventricular ejection fraction (LVEF)
• Efficacy: Diary (Days 1–6) recorded the onset and duration of emetic episodes and nausea severity (Visual Analog Score [VAS] 0–100). They also recorded the achievement of complete response (CR, no emesis, no rescue medication) or no significant nausea (VAS score of < 25 mm) during the acute (0–24 hour), delayed (25–120 hour), and overall (0–120 hour) phases after the start of chemotherapy.

• Baseline sample/group differences of import
• Subject withdrawals ≥ 10%  
• Other limitations/explanation: Patients participated in up to six cycles (98% completed one cycle, 75% completed four cycles, and 40% completed six cycles).