Cancer Pain

Overview

• Reassure patients and family caregivers that most pain can be relieved safely, quickly and effectively (APS Grade A).
• Pain should be assessed on a regular basis (NCCN Category 2A).
• Patient-based education may be associated with modest reductions in cancer pain (level 2 [mid-level] evidence).
• Anticipate and treat adverse effects associated with analgesics (NCCN Category 2A).
• Provide psychosocial support and skills training to patient and family members/caregivers (NCCN Category 2A).
• Optimize use of integrative physical and cognitive methods of pain control (NCCN Category 2A).
• Analgesics
  • Consider acetaminophen or nonsteroidal anti-inflammatory drugs (NSAIDs) for mild cancer pain (NCCN Category 2A).
  • Opioids used for moderate or severe pain which impairs function or quality of life, for which potential benefits outweigh risks, and no alternative has better risk/benefit profile.
    • Opioid prescription management should include written agreement between physician and patient (APS Grade B)
    • Prophylaxis against constipation with stool softeners and motility agents (APS Grade B).
  • Use transdermal fentanyl only in patients tolerant to opioid therapy (NCCN Category 2A).
• Adjunctive medications
  • Gabapentin not clearly effective for cancer-related neuropathic pain (level 2 [mid-level] evidence).
  • Antidepressants have limited evidence for cancer-related neuropathic pain but may reduce postoperative neuropathic pain in breast cancer patients (level 2 [mid-level] evidence).
  • Cannabinoids for cancer pain have very limited evidence; Sativex approved for cancer pain in Canada, United Kingdom, and Catalonia region of Spain.
  • Corticosteroids (as adjuvant to opioids in advanced cancer) may be ineffective for pain but might improve well-being (level 2 [mid-level] evidence).
  • Anxiolytics for anxiety related to anticipation of painful events and procedures (NCCN Category 2A).
• Management of cancer pain syndromes
  • Treatments for bone pain
    • Bisphosphonates appear effective for painful bone metastases (level 2 [mid-level] evidence).
      • Zoledronic acid, ibandronate, and pamidronate may have similar efficacy for pain relief in patients with painful bony metastases (level 2 [mid-level] evidence).
      • Zoledronic acid may have lower incidence of hypercalcemia (level 3 [lacking direct] evidence).
    • Denosumab (Xgeva) FDA approved for prevention of skeletal-related events including bone fractures from cancer and bone pain requiring radiation.
    • Calcitonin not clearly effective for cancer pain from bone metastases (level 2 [mid-level] evidence).
    • Single fraction radiation therapy appears as effective as multiple fractions for relieving metastatic bone pain, but associated with higher re-treatment and pathological fracture rates (level 2 [mid-level] evidence).
    • Radiofrequency ablation reported to be effective for pain relief of bony metastases (level 3 [lacking direct] evidence).
    • Radioisotopes may provide pain relief in patients with metastatic bone pain (level 2 [mid-level] evidence).
    • Vertebroplasty and kyphoplasty reported to reduce pain in patients with cancer related vertebral fracture (level 3 [lacking direct] evidence).
  • Consider NSAIDs or corticosteroids for treatment of pain associated with inflammation (NCCN Category 2A).
  • For treatment of pain associated with bowel obstruction, consider palliative surgery, radiation, or chemotherapy if cancer itself is cause of bowel obstruction (NCCN Category 2A).
  • Treatment of nerve pain
    • Antidepressants and anticonvulsants are first-line treatment for neuropathic pain (NCCN Category 2A)
    • Consider corticosteroids for nerve compression or inflammation (NCCN Category 2A)
• Invasive pain management considerations
  • Indwelling epidural catheters may be associated with risk for infections (level 2 [mid-level] evidence)
  • Intrathecal ziconotide (Prialt) reduces pain in adults with cancer or AIDS and pain refractory to opioids (level 1 [likely reliable] evidence)
  • Celiac plexus block may reduce opioid use and constipation and slightly reduce pain in adults with pancreatic cancer pain (level 2 [mid-level] evidence); chemical splanchnicectomy reduces pain in patients with unresectable pancreatic cancer (level 1 [likely reliable] evidence)
• Complementary therapies
  • Acupuncture may reduce cancer-related pain (level 2 [mid-level] evidence).
  • Hypnotherapy may be associated with pain reduction in advanced cancer (level 2 [mid-level] evidence).
  • Massage therapy reduces pain intensity in patients with metastatic bone pain (level 1 [likely reliable] evidence).
  • Music intervention reduces anxiety and pain (level 1 [likely reliable] evidence) and may improve mood (level 2 [mid-level] evidence) in patients with cancer.
  • Transcutaneous electrical nerve stimulation (TENS) for treatment of cancer-related pain in adults has insufficient evidence of effect.
  • Psychosocial interventions may reduce cancer pain (level 2 [mid-level] evidence).

General Information

Description

• Pain is one of the most common symptoms in cancer patients.
• Cancer pain can be due to direct tumor invasion of bones, nerves, soft tissues, ligaments, and fascia.
• Pain can also result from cancer-related treatments including chemotherapy, radiation therapy, and surgery.

Types

• Multiple taxonomies of pain exist.
• Descriptions of various types of cancer pain include:
  • acute
  • chronic
  • nociceptive (somatic)
  • visceral
  • neuropathic
• Physiological types
  • nociceptive
    • pain caused by stimulation of pain receptors in cutaneous and deeper musculoskeletal structures
    • associated with tissue injury from surgery, trauma, inflammation, or tumor
  • somatic
    • arises from direct injury to bones, tissue or tendons
    • sometimes considered synonymous with nociceptive pain
    • often includes metastatic bone pain, postsurgical incisional pain, and musculoskeletal inflammation and spasm
  • visceral
    • arises from organ damage or tumor infiltrations, compression or distortion of organs within pelvis, abdomen or thorax
    • may be characterized as nociceptive
  • neuropathic
    • may be directly related to malignant disease, such as tumor infiltration of peripheral nerves, plexuses, roots or spinal cord
    • may arise from treatment side effects, such as surgery, chemotherapy, other drug-induced neuropathy or neuritis and radiation-induced injury to peripheral nerves and spinal cord

Incidence/Prevalence

• Prevalence of cancer pain in patients with cancer ranges from 14%-100%
  • Based on review of 28 epidemiological surveys
  • Reference - Cancer Invest 2005;23(2):182

Causes

• Metastases
• Treatment side effects
  • Radiation
  • Chemotherapy (contributing to peripheral neuropathies)
  • Surgery, possibly resulting directly from
    • direct nerve injury
    • inflammation
    • postamputation phantom pain conditions
    • development of complex regional pain syndrome
• In advanced disease
  • Two-thirds due to tumor infiltration, with direct invasion into
    • bone
    • soft tissue
    • nerves
    • ligaments
    • fascia
  • Almost one-quarter due to treatments for cancer

Recommendations

World Health Organization (WHO)

• World Health Organization's three-step approach
  • for mild pain, use non-opioids (non-steroidal anti-inflammatory drugs [NSAIDs]) and/or adjuvant medications
  • for moderate pain (or persistent or increasing pain), use weak opioids (such as codeine) and/or non-opioids and adjuvant medications
  • for severe pain (or persistent, increasing pain), use strong opioids (such as morphine) and/or non-opioids and adjuvant medications
  • Reference - World Health Organization Pain Ladder
• World Health Organization (WHO) guidelines on persisting pain in children
  • Optimal pain management may require a comprehensive approach comprising a combination of strategies
    • nonopioid
    • opioid analgesics
    • adjuvants
    • nonpharmacological strategies
  • Clinical recommendations
    • use analgesic treatment in two steps according to child’s level of pain severity
    • paracetamol and ibuprofen are medicines of choice in first step (mild pain)
    • both paracetamol and ibuprofen need to be made available for treatment in first step
    • use strong opioid analgesics for relief of moderate to severe persisting pain in children with medical illnesses
    • use morphine as first-line strong opioid for treatment of persisting moderate to severe pain in children with medical illnesses
    • insufficient evidence to recommend any alternative opioid in preference to morphine as opioid of first choice
    • consider alternative opioid analgesics to morphine in consideration of safety, availability, cost and suitability, including patient-related factors
    • use immediate-release oral morphine formulations for treatment of persistent pain in children with medical illnesses
    • consider child-appropriate prolonged-release oral dosage forms
    • switching opioids and/or route of administration in children in presence of inadequate analgesic effect with intolerable side-effects
    • consider alternative opioids and/or dosage forms as an alternative to oral morphine
    • do not routinely rotate opioids
    • opioids recommended to be administered orally
    • consider alternative routes of administration when oral route is not available (based on clinical judgement, availability, feasibility and patient preference)
    • do not administer opioids by intramuscular route in children
    • carefully distinguish between
      • end-of-dose pain episodes
      • incident pain related to movement or procedure
      • breakthrough pain
    • in children with persisting pain, use regular medication to control pain and also appropriate medicines for breakthrough pain
  • Reference - WHO 2012 PDF

American Pain Society

• Overview
  • assess for all types of acute and chronic pain and chose appropriate treatment regimens based on underlying mechanisms causing pain (APS Panel consensus)
  • reassure patients and family caregivers that most pain can be relieved safely, quickly and effectively (APS Grade A)
  • include patient and family caregiver education on pain management as part of treatment plan and encourage active participation in pain management (APS Grade A)
  • when choosing pain management strategies, collaborate with patients and family caregivers and take into account cost and availability of treatment options (APS Panel consensus)
  • provide clinicians with basic and ongoing professional education to assess and manage pain effectively (APS Panel consensus)
• Pain assessment
  • perform comprehensive assessment at each visit (outpatient and inpatient), using patient's self-report as foundation of assessment (APS Grade A)
  • include (APS Grade B)
    • detailed history to assess for persistent and breakthrough pain and its effects on function
    • psychosocial assessment
    • physical exam
    • diagnostic evaluation of signs and symptoms associated with common cancer pain presentations and syndromes
  • use valid pain assessment tools to regularly evaluate and document (APS Grade A)
    • pain intensity
    • effectiveness of pain management plan
  • determine if patient has common cancer pain presentation or syndrome in order to minimize morbidity associated with unrelieved pain through prompt diagnosis and treatment (APS Grade B)
  • with a change in pain or new pain (APS Grade B)
    • perform comprehensive pain assessment
    • perform diagnostic evaluation
    • modify pain management plan
  • use tailored strategies to assess pain in special populations including (APS Grade A)
    • very young children
    • very old adults
    • cognitive impaired
    • known or suspected substance abusers
    • non-English speaking persons
  • show patients and family caregivers how to complete a pain management diary (APS Grade B)
  • be aware of preferences and needs of patients whose education or cultural traditions may affect communication about pain (APS Grade B)
• Pain management
  • develop systematic approach to pain management and teach patients/family caregivers how to use effective strategies for optimal pain control (APS Grade B)
  • base initial treatment on severity of pain as reported by the patient (APS Grade B)
  • provide analgesic medication prescription and instruct patients to (APS Panel consensus)
    • have prescription filled
    • take medication if unexpected pain occurs
    • call healthcare provider for appointment to evaluate pain problem
  • begin bowel regimen to prevent constipation when patient begins opioid analgesic (APS Grade B)
  • adjust opioid doses for each patient to achieve pain relief with acceptable level of side effects (APS Grade A)
  • once patient's pain intensity and dose are stabilized, give long-acting opioid on around-the-clock basis, plus immediate-release opioid as needed for breakthrough pain (APS Grade A)
  • do not use meperidine for chronic cancer pain (APS Grade B)
  • avoid intramuscular administration (APS Grade B)
    • painful
    • absorption not reliable
  • before considering spinal analgesics, use optimally titrated doses of opioids and maximal safe and tolerable doses of coanalgesics through other routes of administration (APS Panel consensus)
  • monitor for and prophylactically treat opioid-induced side effects (APS Grade B)
  • in rare instance when naloxone is indicated for reversal of opioid-induced respiratory depression, titrate it by giving incremental doses that improve respiratory function but do not reverse analgesia (APS Grade B)
  • provide patients and family caregivers with accurate and understandable information about effective cancer pain management, the use of analgesic medications, other methods of pain control, and how to communicate effectively with clinicians about unrelieved cancer pain (APS Grade A)
  • provide patients with written pain management plan (Grade B)
  • clarify myths and misconceptions about pain and pain management and reassure patients and family caregivers that cancer pain can be relieved and that addiction and tolerance are not problems associated with effective cancer pain management (APS Grade B)
  • cognitive and behavioral strategies may be used as part of cancer pain management adjunctive to analgesic medications (APS Grade B)
• Management of procedure-related pain in children and adults
  • give patients information about expected quality and duration of sensations experienced during painful procedure (APS Grade A)
  • treat procedure-related pain prophylactically with analgesics and/or sedation (APS Grade A)
  • give safe, monitored procedural sedation to patients who experience distress from painful procedures during diagnosis and treatment of cancer (APS Grade B)
  • if patients decline procedural sedation, offer nonpharmacologic alternatives to decrease pain (APS Grade A)
• Quality improvement in cancer pain management
  • implement formal process of evaluation and management of cancer pain throughout all stages of disease process and across all practice settings (APS Grade B)
  • designate one person in each practice setting to be responsible for pain management (APS Grade C)
  • evaluate quality of pain management during transition points (such as from hospital to home), to ensure optimal pain management is achieved and maintain (APS Grade B)
• Reference - American Pain Society (APS) guideline for management of cancer pain in adults and children

National Comprehensive Cancer Network (NCCN)

Pain screening and Assessment

• screen patient for pain (NCCN Category 2A)
• if no pain present, rescreen patient at each visit (NCCN Category 2A)
• if pain is present
  • use one of the following pain intensity rating scales to determine levels of current, worst, usual, and least pain in the past 24 hours (NCCN Category 2A)
    • Numerical Rating Scale
      • numerical rating scale assesses pain on scale from 0 (no pain) to 10 (worst pain you can imagine)
      • categorical scale assess pain using 4 categories
        • none 0
        • mild 1-3
        • moderate 4-6
        • severe 7-10
    • The Faces Pain Rating Scale - Revised assesses pain using drawing of faces with different expressions portraying no pain to very much pain
  • treat severe, uncontrolled pain immediately (NCCN Category 2A)
  • conduct comprehensive pain assessment to determine (NCCN Category 2A)
    • cause of pain
    • pathophysiology of pain
    • presence of specific cancer pain syndrome
    • patient goals for comfort and function
• anticipate anxiety about painful events and procedures and offer analgesics (topical, local or systemic) and anxiolytics for procedures that often cause pain or anxiety (NCCN Category 2A)
• comprehensive pain assessment
  • patient self-report of pain is sufficient to determine level of pain
  • goal is to find cause of pain and determine best therapy
  • individualized treatment of pain is based on
    • characteristics of the pain
    • cause of pain
    • patient's clinical condition
    • patient's goals
  • use alternative methods to determine level of pain
    • in non-verbal patient
      • observe patient behavior
      • obtain family/caregiver input on patient's behavior
      • evaluate patient response to pain medication and nonpharmacological interventions
    • in patients with advanced dementia, use of 1 of many published pain assessment tools found at City of Hope Pain & Palliative Care Resource Center, including
      • The Assessment of Discomfort in Dementia (ADD) protocol
      • Checklist of Nonverbal Pain Indicators (CNPI)
      • The Pain Assessment in Advanced Dementia (PAINAD) scale
    • for patients who are intubated or unconscious, use 1 of many pain assessment tools, including
      • Behavioral Pain Scale (BPS) in adult patients and those in intensive care
      • Critical-Care Pain Observation Tool (CPOT) in adult patients and those in intensive care
  • use culturally and linguistically appropriate materials and consider employing a trained interpreter when appropriate
  • determine cause and pathophysiology of pain by medical history, physical exam, laboratory tests, and imaging studies
  • determine the patient experience of the pain, including
    • location, referral pattern, radiation
    • intensity of pain
      • in last 24 hours and currently
      • at rest and with movement
    • interference with activities including general activity, mood, walking, ability to work, relationships, sleep, appetite, and general quality of life
    • timing (onset, duration, course, persistence
    • description or quality of pain
      • consider somatic pain in skin, muscle, or bone if pain is described as aching, stabbing, throbbing, or pressure
      • consider visceral pain in organs or viscera if pain is described as gnawing, cramping, aching, or sharp
      • consider neuropathic pain caused by nerve damage if pain is described as burning, tingling, shooting, or electric/shocking
    • factors that aggravate or alleviate pain
    • other current symptoms and symptom clusters
  • obtain current pharmacologic and nonpharmacologic pain management plan; if medications are used, determine
    • medications used (prescription and over-the-counter)
    • dose, route of administration, and frequency
    • current prescriber
  • determine response to current therapy, including
    • achievement of adequate pain relief
    • adherence to medication plan
    • adverse effects
  • determine if patient is experiencing breakthrough pain with current treatment regimen
  • obtain history of prior pain treatments
    • reason for use
    • length of use
    • response
    • reason for discontinuing
    • adverse effects
  • other factors to consider in pain assessment include
    • attitudinal, cultural, and spiritual beliefs around pain and pain medications
    • patient goals and expectations for pain management
    • risk of opioid misuse/abuse

Management of Pain not Related to Oncologic Emergency

• Management of pain not related to oncologic emergency
  • in opioid-naive patients
    • for all pain levels
      • appropriate dose relieves pain throughout dosing interval but does not cause unmanageable adverse effects (NCCN Category 2A)
      • titrate with caution in patients with certain risk factors, including (NCCN Category 2A)
        • decreased hepatic or renal function
        • chronic lung disease
        • upper airway compromise
        • sleep apnea
        • poor performance
      • oral route of administration is most common but consider alternate routes to maximize patient comfort (NCCN Category 2A)
        • patient referral recommended when (NCCN Category 2A)
          • patient may benefit from nerve block
          • adequate analgesia cannot be obtained
          • patient experiences intolerable adverse effects
        • consider interventional strategies if determined they may provide sufficient benefit, such as (NCCN Category 2A)
          • regional infusion methods (requires infusion pump), including
            • epidural
              • for infusion of opioids, local anesthetics, and clonidine
              • for acute postoperative pain
              • monitor for catheter displacement and infection when used for several days or weeks
            • intrathecal for infusion of opioids, local anesthetics, clonidine, and ziconotide
            • regional plexus
              • for infusion of local anesthetic
              • to anesthetize a single extremity
              • monitor for catheter displacement and infection when used for several days or weeks
          • percutaneous vertebroplasty/kyphoplasty
          • consider neurodestructive procedures for well-localized pain syndromes although spinal analgesics are more common, including
            • peripheral neurolysis for head and neck
            • brachial plexus neurolysis for upper extremity
            • epidural or intrathecal, intercostal, or dorsal root ganglion neurolysis for thoracic wall
            • celiac plexus block or thoracic splanchnicectomy for upper abdominal pain
            • superior hypogastric plexus block for midline pelvic pain
            • intrathecal neurolysis, midline myectomy, superior hypogastric plexus block or ganglion impar black for rectal pain
            • cordotomy for unilateral pain
            • intrathecal L/S phenol black
          • neurostimulation procedures for cancer-related symptoms such as
            • peripheral neuropathy
            • neuralgias
            • complex regional pain syndrome
          • radiofrequency ablation for bone lesions
      • anticipate and treat adverse effects associated with analgesics (NCCN Category 2A)
        • educate patient and caregiver on how to anticipate adverse effects and on management of pain and adverse effects (NCCN Category 2A)
        • for prevention and treatment of opioid-related adverse effects, see Opioids for chronic cancer pain for details
      • consider adjuvant analgesics for specific pain syndrome, particularly in patients who are partially responsive to opioids (NCCN Category 2A)
        • increase dose until
          • analgesia is achieved
          • adverse effects become unmanageable
          • conventional maximum dose is reached
        • consider other symptoms and comorbidities when selecting a drug
        • communicate with patient that treatment is often trial and error as to avoid discouragement
      • provide psychosocial support (NCCN Category 2A)
        • support includes
          • informing patient and family/caregivers that emotional reactions to pain medication is normal and that they are evaluated and treated as part of pain management
          • informing patient that pain will be addressed
          • describing plan and time frame for results
          • informing patient that there are alternative methods to effectively manage pain or other noxious symptoms
          • provide education and support to family members to communicate that management of pain is a team effort
        • skills training includes
          • learning of coping skills to provide pain relief, enhance a sense of personal control over pain, and refocus efforts on increasing quality of life, including
            • methods for managing acute and chronic pain such as
              • Lamaze-type breathing exercises
              • distraction techniques
            • other methods for managing chronic pain such as
              • guided imagery
              • graded task assignments
              • hypnosis to maximize function
            • increasing assertiveness to allow patient to maximize comfort
      • provide patient and family/caregiver education (NCCN Category 2A)
        • assess for
          • meaning and consequences of pain for patient and family/caregiver
          • literacy to ensure family/caregiver understands
          • existing knowledge of pain and pain treatment
        • advise family member(s)/caregiver that
          • relief of pain is important and there is no benefit to suffering with pain
          • pain medication can usually control pain and taking an analgesic on a regular schedule can improve pain control for persistent pain
          • morphine and morphine-like medications
            • most commonly used medications for relief of severe pain
            • should only be used to treat pain and not as a sleep aid or to relieve anxiety or other mood issues
            • other treatment options are available should these medications not work
          • patients with the following risk factors may be at increased risk for opioid misuse/abuse
            • history of prescription or illicit drug abuse, or alcohol dependence
            • history of binge drinking or having friends/family members who binge drink
            • family history of substance abuse
            • history of anxiety, depression, or attention deficit hyperactivity disorder
            • history of sexual abuse
          • patients with history of opioid misuse or abuse may require higher doses for pain control
      • optimize integrative interventions, including (NCCN Category 2A)
        • physical methods, such as
          • bed, bath, and walking supports
          • positioning instruction
          • physical therapy
          • pacing of activities
          • massage
          • heat or ice
          • transcutaneous electrical nerve stimulation (TENS)
          • acupuncture or acupressure
          • ultrasonic stimulation
        • cognitive methods, such as
          • imagery
          • hypnosis
          • distraction training
          • relaxation training
          • active coping training
          • graded task assignments, setting goals, pacing, and prioritizing
          • cognitive behavioral training
      • consider nonsteroidal anti-inflammatory drugs (NSAIDs) or acetaminophen for pain (NCCN Category 2A)
      • consider hospital or inpatient hospice admission for acute severe pain or pain crisis in order to achieve patient-specific goals for comfort and function (NCCN Category 2A)
    • for mild pain (rated 1-3), in addition to above management plan, consider
      • nonopioid analgesics such as NSAIDs or acetaminophen (NCCN Category 2A)
      • slow titration of a short-acting opioid (NCCN Category 2A) for pain not controlled with a NSAID or acetaminophen
    • for moderate pain (rated 4-6) or severe pain (rated 7-10), in addition to above management plan, initiate short-acting opioid by rapid titration (NCCN Category 2A)
  • in opioid tolerant patients, increase opioid dose equivalent to 10%-20% of total opioid taken in previous 24 hours in patients (NCCN Category 2A)
  • subsequent pain management and ongoing care for all patients
    • for all pain levels
      • start regular schedule of opioid with rescue dose if needed for persistent pain (NCCN Category 2A)
      • continue bowel regimen (NCCN Category 2A)
    • if pain is rated moderate-to-severe after initial dosing regimen
      • reevaluate opioid titration for severe pain (NCCN Category 2A)
      • continue opioid titration for moderate pain (NCCN Category 2A)
      • conduct comprehensive pain assessment (NCCN Category 2A)
      • consider consult with pain specialist or opioid rotation (NCCN Category 2A)
    • if pain is mild, reassess and modify treatment to minimize adverse effects (NCCN Category 2A)
    • reevaluate patient at each visit to determine if patient goals have been achieved
      • if goals achieved, the following are recommended (NCCN Category 2A)
        • switching from parenteral to oral or transdermal administration if possible
        • simplifying treatment regimen
        • assessing pain during each visit or each day for inpatients
        • monitoring use of analgesics as prescribed, particularly in patients at high risk or with a history of abuse
        • giving patient written follow-up pain plan, including list of prescribed medications
      • if goals not achieved, consider (NCCN Category 2A)
        • consulting with pain management specialist or palliative care
        • interventional strategies or other treatments

Management of Pain Related to Oncologic Emergency

• Oncologic emergencies include
  • bone fracture of weight-bearing bone
  • neuraxial metastases with threatened neural injury
  • infection
  • obstructed or perforated viscus
• For management of pain related to oncologic emergency, treatment includes pain management as outlined above plus treatment of emergency (NCCN Category 2A)

Management of Cancer Pain Syndromes

• Management for cancer pain syndromes
  • consider trial of the following treatment regimens to complement management of cancer pain with opioids
    • NSAIDs or corticosteroids for pain associated with inflammation (NCCN Category 2A )
    • for bone pain without fracture of weight-bearing bone (NCCN Category 2A)
      • NSAIDs
      • bone-modifying agents such as bisphosphonates or denosumab
      • hormonal therapy or chemotherapy, corticosteroids, or systemic radioisotopes for diffuse bone pain
      • local radiation therapy, nerve block, vertebroplasty, or radiofrequency ablation for local bone pain
      • consultation with orthopedic and pain specialist
    • for pain associated with bowel obstruction (NCCN Category 2A)
      • evaluate cause of obstruction; if cause is cancer itself consider
        • palliative surgery
        • radiation therapy
        • chemotherapy
      • other palliative management options include
        • bowel rest
        • nasogastric suction
        • percutaneous gastrostomy drainage
        • corticosteroids
        • histamine 2 blockers
        • anticholinergics
        • octreotide
    • for treatment of nerve pain (NCCN Category 2A)
      • corticosteroids for nerve compression or inflammation
      • antidepressants and anticonvulsants are first-line treatment options for neuropathic pain; also consider topical agents such as lidocaine patch or corticosteroids
      • consider referral to pain specialist or use of interventional strategies for refractory pain
    • consider radiation therapy, hormones, or chemotherapy for painful lesions that are likely to respond to antitumor agents (NCCN Category 2A )

Scottish Intercollegiate Guidelines Network (SIGN)

• Major recommendations
  • Assessment of pain
    • before treatment, accurate assessment should be performed to determine cause, type and severity of pain and its effects on the patient (SIGN Grade D)
    • patient should be prime assessor of pain (SIGN Grade D)
    • how should pain be assessed?
      • patients should have treatment outcomes monitored regularly using (SIGN Grade D)
        • visual analog scales
        • numerical rating scales
        • verbal rating scales
      • self-assessment pain scales should be used in patients with cognitive impairment, when feasible (SIGN Grade C)
      • observational pain rating scales should be used in patients who cannot complete self-assessment scale (SIGN Grade C)
  • Psychosocial issues
    • Psychological distress
      • comprehensive pain assessment should include screening for psychological distress (SIGN Grade B)
      • cognitive behavior therapy should be part of comprehensive treatment program for pain and related distress and disability (SIGN Grade A)
    • Psychological factors and adherence to treatment
      • patient's beliefs about pain should be discussed as part of comprehensive biopsychosocial assessment (SIGN Grade D)
      • patients should be educated about pain control measures available (SIGN Grade C)
  • Principles of pain management
    • patients should be given information about pain and pain management and be encouraged to take active role (SIGN Grade B)
    • World Health Organization (WHO) cancer pain relief program
      • principles of treatment from WHO cancer pain relief program should be followed (SIGN Grade D)
      • using WHO analgesic ladder
        • treatment should match step of ladder appropriate for severity of pain (SIGN Grade B)
        • analgesia should be adjusted when severity of pain changes (SIGN Grade B)
        • analgesia for continuous pain should be prescribed on regular basis and not as required (SIGN Grade D)
        • appropriate analgesia for breakthrough pain should be prescribed (SIGN Grade D)
  • Treatment with non-opioid drugs
    • paracetamol (acetaminophen) and non-steroidal anti-inflammatory drugs
      • patients at all steps of WHO analgesic ladder should receive paracetamol and/or non-steroidal anti-inflammatory drug, unless contraindicated (SIGN Grade A)
      • patients on non-steroidal anti-inflammatory drug and at high risk of gastrointestinal complications should be prophylactically given one of following (SIGN Grade A)
        • misoprostol 800 mcg/day
        • standard dose proton pump inhibitors
        • double dose histamine-2 receptor antagonists
    • bisphosphonates should be considered as part of therapeutic regimen for metastatic bone disease (SIGN Grade B)
    • neuropathic pain should be treated with either tricyclic antidepressants (such as amitriptyline or imipramine) or anticonvulsants (such as gabapentin, carbamazepine or phenytoin) with careful monitoring of side effects
    • cannabinoids not recommended (SIGN Grade A)
  • Treatment with opioid drugs
    • choice of opioid
      • mild-moderate pain (step 2 of the World Health Organization [WHO] ladder) (SIGN Grade D)
        • mild-moderate pain is score 3-6 out of 10 on visual analog scale or numerical rating scale
        • weak opioids (for example, codeine) in combination with non-opioid analgesic
      • moderate-severe pain (step 3 of the WHO ladder) (SIGN Grade D)
        • oral morphine recommended as first line therapy for severe pain
        • diamorphine recommended as first line subcutaneous therapy for severe pain
      • breakthrough pain (SIGN Grade D)
        • breakthrough analgesia used for moderate or severe breakthrough pain
        • when using oral morphine for breakthrough pain
          • dose should be one-sixth of 24-hour morphine dose
          • dose should be increased appropriately whenever 24-hour dose is increased
      • patients with renal impairment – all opioids should be used with caution and at reduced doses and/or frequency (SIGN Grade C)
    • administration of opioids (SIGN Grade D)
      • consider continuous subcutaneous infusion of opioids for patients unable to take opioids orally
        • simpler to administer
        • as effective as continuous IV infusion
      • staff who prepare drug combinations for continuous subcutaneous infusion should be aware of stability of commonly used drugs; obtain advice on use of other combinations from palliative care specialists
      • patients with stable pain on oral morphine should be prescribed once or twice daily modified release preparation
      • patients with stable pain on oral oxycodone should be prescribed twice daily modified release preparation
  • Non-pharmacological treatment
    • patients with painful bone metastases not responding to medications should be considered for external beam radiation therapy or radioisotope treatment (SIGN Grade B)
    • cementoplasty (SIGN Grade D)
      • patients with pain from malignant vertebral collapse not responding to medications should be considered for vertebroplasty
      • patients with pain and reduced mobility from pelvic bone metastases not responding to medications should be considered for percutaneous cementoplasty
    • to improve pain control and quality of life in difficult to control pain, anaesthetic interventions should be considered, such as (SIGN Grade B)
      • celiac plexus block
      • neuraxial opioids
  • Reference - Scottish Intercollegiate Guidelines Network (SIGN) national clinical guideline on control of pain in adults with cancer (SIGN 2008 Nov PDF)

Choosing Wisely

• American Academy of Hospice and Palliative Medicine does not recommend more than a single fraction of palliative radiation for an uncomplicated painful bone metastasis (Choosing Wisely 2013 Feb 21)

• Canadian Oncology Societies recommend against more than a single fraction of palliative radiation for an uncomplicated painful bone metastasis (Choosing Wisely Canada 2014 Oct 29)

• American Society for Radiation Oncology recommends against routinely using extended fractionation schemes (> 10 fractions) for palliation of bone metastases (Choosing Wisely 2014 Sep 15)

Pain Assessment

Review of Pain Assessment

• Conduct upon admission to healthcare facility, both inpatient and outpatient.
• Reassess on regularly scheduled basis.
• Patient should be actively involved in assessment and pain management plan
• Include:
  • location
  • quality/description
  • intensity
  • duration
  • alleviating and aggravating factors
  • associative factors
  • effect of pain on patient's life
• Recommendations if patient is nonverbal (such as elderly with advanced dementia, patients who are intubated or unconscious) include:
  • obtain self-report when appropriate
  • investigate potential causes of pain
  • observe behaviors using behavioral pain tool
  • use surrogate reporting
  • initiate analgesic trial.
• Reference - Medsurg Nurs 2008 Dec;17(6):413

Pain Assessment Instruments

• systematic review found no pain assessment instrument with established validity and reliability for use in older persons with cognitive impairment (J Am Geriatr Soc 2005 Feb;53(2):319)

Follow up

• Follow-up important for achieving pain control.
• Change pain regimen as necessary, or document as to why no change was made:
  • consider adjusting medications
  • consider switching to or adding on other drug classes or modalities
  • ensure timely response to moderate or severe pain
  • consider other treatments such as radiation therapy
  • consider other procedures such as nerve blocks.
• Use preventive approach to pain management with analgesics:
  • analgesics are more effective around-the-clock, rather than as-needed, with predictable pain like cancer pain
  • around-the-clock schedule maintains therapeutic blood levels of analgesics.
  • Reference - Medsurg Nurs 2008 Dec;17(6):413

Patient Education and Self-Management

Barriers to Pain Control

• Patient barriers to pain control may include:
  • fear of addiction
  • fear of developing tolerance
  • fear of masking disease progression
  • fear of physician fatigue or annoyance

Analgesics

Acetaminophen

• Consider acetaminophen for mild cancer pain (NCCN Category 2A)
  • 650 mg every 4 hours or 1 g every 6 hours for a maximum daily dose of 4 g/day in adults with normal liver function
  • consider lower maximum daily dose to ≤ 3 g/day for chronic administration
  • do not use with combination opioid-acetaminophen medications to prevent excess acetaminophen dosing
• Often combined with short-acting opioids if initial therapy unsuccessful
  • may provide dose-sparing effect that reduces amount of opioid necessary for analgesia and limit opioid-induced adverse effects
  • determine if patient also taking other multi-ingredient products (cold/flu remedies) containing acetaminophen for pain or other conditions
• Acetaminophen has been considered a non-steroidal anti-inflammatory drug (NSAID) with very weak anti-inflammatory activity (Clin Infect Dis 2000 Oct;31 Suppl 5:S202)

Nonsteroidal anti-inflammatory Drugs (NSAIDs)

• Consider NSAIDs for mild cancer pain, including patients with pain associated with inflammation and those with bone pain without oncologic emergency (NCCN Category 2A)
  • 400 mg 4 times/day to a maximum dose of 3,200 mg/day
  • consider short-term use of ketorolac 15-30 mg IV every 6 hours for a maximum of 5 days
  • consider topical NSAID-diclofenac gel 1% 4 times/day or diclofenac patch 180 mg 1-2 patches/day
  • use with caution due to high risk for renal, gastrointestinal, or cardiac toxicity, thrombocytopenia, or bleeding disorder in cancer patients
  • concomitant NSAID and chemotherapy use may increase adverse effects associated with chemotherapy
  • opioid analgesics may be a safe and effective alternative to NSAIDs
• May be used as monotherapy or in conjunction with opioids to reduce moderate to severe pain
• May offer opioid-sparing effect
• Clinician should consider
  • adverse effects, especially gastrointestinal and renal
  • co-existing conditions such as thrombocytopenia or neutropenia
  • antipyretic and anti-inflammatory properties in neutropenic patients masking signs and symptoms of infection

• Aspirin
  • maximum analgesic effect with 650-1,300 mg
  • effective for most mild to moderate pain, but mostly used in low doses as platelet inhibitor (inhibits for 8-10 days)
  • adverse reactions
    • do not use in children or adolescents with viral syndromes due to risk of Reye syndrome
    • gastropathy and salicylate intoxication with high doses
    • can cause asthma if aspirin-sensitive
• Non-selective NSAIDS
  • inhibit cyclooxygenase (COX) enzyme
  • reported to be more effective in pain relief than aspirin or acetaminophen alone and some oral opioid combinations
  • adverse effects
    • may cause asthma if aspirin-sensitive
    • decreased renal blood flow (risk factors include older age, heart failure, renal insufficiency, ascites, volume depletion and diuretic therapy)
    • gastrointestinal adverse effects can occur and may be exacerbated by alcohol, older age or peptic ulcers
    • cardiovascular toxicity may occur
  • combinations with proton-pump inhibitor or misoprostol are available and may reduce risk with chronic NSAID treatment
• Dosing of some NSAIDs
  • aspirin 325-650 mg every 4-6 hours, maximum dose 4,000 mg/day (available in chewable, buffered, enteric-coated and extended-release)
  • diflunisal 750-1,000 mg initially, then 500 mg every 8-12 hours, maximum dose 1,500 mg/day
  • choline magnesium trisalicylate 750-1,500 mg every 8-12 hours, maximum dose 3,000 mg/day
  • acetaminophen 500-1,000 mg every 4-6 hours, maximum dose 4,000 mg/day
  • ibuprofen 200-400 mg every 4-6 hours, maximum dose 2,400 mg/day
  • naproxen 500 mg initially, then 250 mg every 6-8 hours OR 500 mg every 12 hours, maximum dose 1,250 mg/day first day then 1,000 mg/day
  • naproxen sodium 550 mg initially, then 275 mg every 6-8 hours OR 550 mg every 12 hours, maximum dose 1,375 mg/day on first day then 1,100 mg/day
    • naproxen sodium nonprescription 220 or 440 mg initially, then 220 mg every 8-12 hours, maximum dose 660 mg/day
  • ketoprofen 25-75 mg every 6-8 hours, maximum dose 300 mg/day
  • ketorolac (only available injectable NSAID formulation available in United States)
    • 30 mg intramuscularly or IV every 6 hours if < 65 years old, maximum dose 120 mg/day
    • 15 mg intramuscularly or IV every 6 hours if > 65 years old, maximum dose 60 mg/day
    • 10 mg orally every 4-6 hours, maximum dose 40 mg (given only as continuation of intramuscular or IV ketorolac)
    • total use 5 days maximum
  • mefenamic acid 500 mg initially, then 250 mg every 6 hours, maximum dose 1,250 mg/day (total duration 1 week maximum)
  • diclofenac potassium 50 mg every 8 hours, maximum dose 150 mg/day.
  • etodolac 200-400 mg every 6-8 hours, maximum dose 1,200 mg
  • flurbiprofen 50-100 mg every 6-12 hours, maximum dose 300 mg (FDA approved for use in osteoarthritis and rheumatoid arthritis only)
  • nabumetone 1,000 mg initially, then 500-750 mg every 8-12 hours, maximum dose 2,000 mg/day (FDA approved for use in osteoarthritis and rheumatoid arthritis only)

Opioids

• Monitor for adverse effects and prophylactically treat opioid-induced side effects including (APS Grade B; NCCN Category 2A):
  • sedation
  • sleep disturbances
  • cardiac effects
  • constipation (use stool softeners and motility agents to prevent constipation)
  • respiratory depression
  • cognitive impairment (caution patient about impaired driving or work safety).
• Oral route of administration is most common but consider alternate routes to maximize patient comfort (NCCN Category 2A); avoid intramuscular administration (APS Grade B).
• Adjust opioid doses for each patient to achieve pain relief with acceptable level of side effects (APS Grade A; NCCN Category 2A).
• Once patient's pain intensity and dose are stabilized, give long-acting opioid on around-the-clock basis, plus immediate-release opioid as needed for breakthrough pain (APS Grade A).
• Conversion from short-acting opioids to once-daily oral extended-release hydromorphone reported to be effective for most patients with chronic cancer pain.
• Do not use meperidine for chronic cancer pain (APS Grade B).
• Consider opioid rotation if pain is not controlled with adequate titration or if adverse effects are persistent (NCCN Category 2A).
• Use transdermal fentanyl only in patients tolerant to opioid therapy (NCCN Category 2A)
  • transdermal fentanyl may result in a tolerable degree of pain with less constipation than oral morphine in chronic cancer pain patients
  • oral or nasal transmucosal fentanyl may decrease pain intensity and may be more effective than oral morphine for management of breakthrough pain.
• Key concerns with opioid use include:
  • potential issues related to narcotic use - prescription drug abuse, addiction, dependence, tolerance, drug diversion
  • drug interactions.

Adjunctive Medications

Anticonvulsants

• Consider anticonvulsants as a first-line treatment option for patients with neuropathic pain (NCCN Category 2A).

Antidepressants

• Consider antidepressants as a first-line treatment option for patients with neuropathic pain (NCCN Category 2A).
• Antidepressants reported to be effective for neuropathic pain include:
  • tricyclic antidepressants
  • duloxetine
  • venlafaxine.

Cannabinoids

• Beliefs, practices, and knowledge regarding medical marijuana use based on survey of 237 medical oncologists in United States can be found in J Clin Oncol 2018 Jul 1;36(19):1957.

Corticosteroids

• Young patient with undiagnosed mass may be contraindication to corticosteroid therapy; corticosteroids may delay diagnosis by causing oncolytic effect on lymphomas and thymomas.
• Pain from nerve compression or inflammation may respond to corticosteroids (Medsurg Nurs 2008 Dec;17(6):413).