cancer%20pain
CANCER PAIN
Cancer pain is an unpleasant sensory & emotional experience due to actual or potential tissue damage in patients with cancer.
Effective pain management in cancer patients with pain is an essential part of oncologic management due to increasing evidence of survival.
Pancreatic, head & neck cancer has a high prevalence of cancer pain.
During initial evaluation, follow-ups and new therapy initiation of patients with cancer, it is essential that they will be screened & evaluated for pain.

Principles of Therapy

  • Symptom control should be prioritized when dealing with cancer pain-
    • Studies revealed that symptom control improves survival rates & quality-of-life
  • Goals of pain control involves optimizing the “4As”: analgesia, activities, adverse effects, & aberrant drug intake
    • Analgesic treatments should be utilized at its maximum potential
    • Return to routine activities must be achieved
    • Adverse effects of treatments should be kept to a minimum
    • Drug intake should be monitored to avoid aberrant drug taking
  • Shifting from high-dose non-opioid analgesics, to non-opiod-opioid combination, to pure opioid preparations are recommended for more effective control of pain to avoid the toxicities of non-opioid agents
  • Opioid rotation should be considered if pain is inadequately controlled & further titration is not possible
  • Extended-release or long-acting formulations are recommended for effective control of chronic persistent pain 
  • Pharmacological cancer pain treatment generally have an oral route of administration & dose of analgesic have an “around the clock” regimen
  • Other routes of administration can be considered eg intravenous (IV), subcutaneous (SC), rectal, transdermal, transmucosal in order that the patient have pain relief & comfort
  • Analgesic regimen is based on pain severity that starts with non-opioid analgesics for mild pain, mild opioid analgesics for moderate pain, & progress to strong opioids for severe pain

Pharmacotherapy

Non-Opioid Analgesics

  • Eg Ketamine, Paracetamol, nonsteroidal anti-inflammatory drugs (NSAIDs)
  • Indicated for treatment of mild to moderate pain
  • Lowest effective dose is recommended in shortest period to control symptoms in order to prevent potential side effects [eg hepatotoxicity, gastrointestinal (GI) bleeding, renal failure & thrombotic cardiovascular events]
  • When used with opioid analgesics, it may produce better pain relief & lower incidence of opioid-related side effects
  • COX-2 inhibitors may be considered for patients with history of gastrointestinal or hematologic diseases
  • Ketamine, a noncompetitive NMDA receptor antagonist, may help provide analgesia & modulate central sensitization, hyperalgesia & opioid tolerance in opioid-resistant cancer pain

Opioid Analgesics

  • Mainstay of analgesic therapy & may be combined with non-opioid drugs such as Paracetamol or nonsteroidal anti-inflammatory drugs & with adjuvant drugs
  • Should be considered for cancer survivors with chronic pain who are unresponsive to non-opioid analgesics & other conservative therapies
  • Weak opioids (eg Tramadol, Dihydrocodeine, Codeine) are indicated for mild to moderate cancer pain
  • Strong opioids/pure agonists (eg Morphine, Oxycodone, Oxymorphone, Fentanyl) are the most commonly used opioids in the management of moderate to severe cancer pain
  • Opioid-naive patients are those who have no history of opioid intake while opioid-tolerant patients are the ones who have previously or have chronically taken opioids for cancer pain relief
  • For opioid-naive patients that are experiencing moderate pain, slow titration of short-acting opioids (Morphine, Hydromorphone, Fentanyl, Oxycodone) is suggested
  • Opioid-naive patients experiencing severe pain should receive rapid titration of short-acting opioids
    • Short-acting formulations have the advantage of rapid onset of analgesic effect
    • Route of administration depends on what is best suited to the patient’s ongoing analgesic needs

Buprenorphine

  • A partial mu-receptor antagonist, is a preferred treatment option for patients with moderate to severe pain with severe renal dysfunction undergoing dialysis
  • Transdermal Buprenorphine is a treatment option for patients with stable opioid requirements for chronic pain

Codeine

  • A weak mu- & delta-opioid receptor agonist
  • Provides little or no direct analgesia especially in patients who are poor metabolizers

Fentanyl

  • A semisynthetic mu-opioid receptor agonist with high lipid solubility
  • For patients whose opioid requirements are stable, who are unable to swallow, cannot tolerate Morphine or with poor compliance
  • Transdermal Fentanyl should only be considered for patients whose pain has previously been managed & was responsive to other opioids, & is not indicated for rapid opioid titration
  • Transmucosal Fentanyl formulations (oral, buccal, sublingual, & intranasal) are effective options for managing cancer patients w/ unpredictable & rapid-onset breakthrough pain
    • It is applicable in patients receiving doses of oral Morphine equivalents of at least 60 mg
    • May be considered in patients who are opioid-tolerant for brief episodes of incident pain not attributed to inadequate dosing of an around-the-clock opioid

Hydrocodone

  • A mu- & delta-opioid receptor agonist used as a mild, initial-use opioid,with varied effective dose
  • Only available in combination with oral agents such as Ibuprofen & Paracetamol

Hydromorphone

  • A mu-opioid receptor agonist & weak delta-opioid receptor agonist with properties identical to Morphine
  • Studies have shown that Hydromorphone can effectively reduce moderate to severe pain in cancer patients previously unresponsive to other analgesics but may be more neurotoxic compared to Morphine

Levorphanol

  • A mu/delta/kappa opioid-receptor & N-methyl-D-aspartate (NMDA)-receptor antagonist with shorter half-life compared to Methadone
  • Efficacy is comparable to Methadone but with lesser adverse effects

Methadone

  • A mu-receptor & N-methyl-D-aspartate (NMDA)-receptor antagonist used as a option for the treatment of cancer-related pain
  • Should be given at lowest dose (50%) during initiation & slowly titrated upwards to prevent adverse effects secondary to its long half-life, high potency, & variations in pharmacokinetics per individual
  • It should be used only as prescribed by a pain specialist of palliative care
Morphine
  • A mu-opioid receptor agonist & weak kappa receptor agonist
  • Standard starting treatment in opioid-naive patients who has moderate to severe cancer pain
  • Oral administration is the preferred route for opioid-naive patients while intravenous (IV) or subcutaneous (SC) route is preferred for patients with severe pain that needs urgent relief

Oxycodone

  • Used as an alternative strong opioid with agonist activity at the mu, delta, & kappa opioid receptors
  •  Analgesic & adverse effects are comparable to that of Morphine for the treatment of cancer-related pain
  • Studies have shown that combination with Naloxone produces analgesia with reduced constipation compared to opioid monotherapy

Oxymorphone

  • A long-acting mu-opioid receptor agonist
  • Should be used with caution in patients with renal dysfunction

Dual Mechanism Opioids

  • Eg Tramadol, Tapentadol
  • Acts on both opioid receptors & neurotransmitter reuptake inhibitor
  • Tapentadol is a μ-opioid receptor & norepinephrine reuptake inhibitor used for moderate-severe pain
  • Tramadol, a weak mu-opioid with modest norepinephrine & serotonin reuptake inhibitor properties, may be used for moderate to moderately severe pain

Opioid Switching (Rotation)

  • Treatment strategy which involves changing of an opioid with an equivalent dose of an alternative opioid to enhance the balance between the analgesic therapy & its side effects
  • It is indicated in patients with:
    • Inadequate pain relief despite appropriate dose titration of the initial opioid
    • Intolerable side effects (eg sedation, nausea, vomiting, constipation)
    • Renal impairment
    • Practical considerations (eg patient preference, inability to swallow, etc)
  • Opioids that can be used for switching are Oxycodone, Fentanyl & Methadone
  • Equianalgesic conversion tables should be the guide in changing one opioid to another or between different routes of administration

Adjuvant Therapy

  • Medications that are coadministered to manage an adverse effect of an opioid or to adjuvant analgesics that are added to enhance analgesia

Analgesics

  • They have primary indications other than pain
  • Also called co-analgesics; may be used alone or in combination with other analgesics including strong opioids
  • Usually used in treatment of bone pain, neuropathic pain, visceral pain

Antidepressants

  • Eg tricyclic antidepressants
  • Studies have shown that it can relieve neuropathic pain

Anticonvulsants

  • Eg Gabapentin, Pregabalin
  • Can be used in the treatment of neuropathic pain, mucositis pain in patients receiving concomitant radiotherapy & chemotherapy

Corticosteroids

  • Have been used in relief of neuropathic pain from spinal cord compression, bone pain, headache from brain metastases, abdominal pain from liver capsule distension or intestinal obstruction

Investigational Agents

  • Nabiximol, a Cannabis sativa extract that contains the cannabinoids D9-tetrahydrocannabinol & cannabidiol, is being studied as an adjunctive therapy for patients whose cancer pain is not completely controlled by opioids

Non-Pharmacological Therapy

Psychosocial Support

  • Cancer pain management goals include the patient’s comfort, function & safety
  • Cognitive behavioral interventions & psychosocial support can help in alleviating the patient’s pain severity but also the psychological distress related to it
  • Cognitive interventions aim to enhance the sense of control over the pain or underlying disease

Physical & Complementary Therapy

  • Exercise can help reduce pain in some cancer patients
  • Massage with or without aromatherapies can give transient relief of pain as well as other cancer-related symptoms
  • It was found that acupuncture can be effective in relieving chronic neuropathic cancer pain

Interventional Techniques

  • Indicated in patients who have significant pain from locally advanced disease, severe neuropathic pain & severe pain on movement
  • Neurolytic sympathetic plexus blocks (ie neurolytic celiac plexus block, splanchnic nerve block, neurolytic superior hypogastric plexus block) involves instilling alcohol or phenol with local anesthetics into the nerve plexus that can ablate the sympathetic nerve supply to painful viscera
    • It can be considered in patients with pain from pancreatic cancer
  • Intrathecal neurolytic saddle block is also one of the interventional techniques
  • Neuraxial opioid therapy (epidural & intrathecal opioids) with or without anesthetics can be used in diffuse pain from advanced cancer
  • Vertebroplasty & kyphoplasty involves the introduction of bone cement directly into cancellous bone of the vertebral body to relieve pain due to spinal metastases, vertebral compression fractures, or spinal instability
    • Kyphoplasty utilizes an intervertebral balloon prior to bone cement injection
    • It can be considered in patients with uncontrolled bone pain from malignant vertebral collapses
  • Orthopedic interventions (eg internal fixation of pathological long bone fractures) can be considered in patients whose life expectancy is more than 4 weeks or who are fit to undergo the procedure to relieve pain
  • Ablative surgery to remove large tumors can improve pain control in some painful fungating breast lesions or large sarcomas if pharmacological intervention did not give optimal pain relief
  • Pain due to malignant bowel obstruction may be relieved by palliative surgical procedures ie colostomy or bypass procedures
  • External beam radiotherapy has been found to be effective in the management of metastatic bone pain & in metastatic spinal cord compression (mSCC)
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