[8.2] 6132 LEC - ONCOLOGY SUPPORTIVE CARE part 2

Cancer Pain Management

• Oral route is preferred when available 

• Choose the analgesic drug and dose to match the degree of pain suffered by the patient 

• should always be administered on a schedule and not on PRN basis 

• Persistent severe pain, use an analgesic with long duration of action to minimize frequency of administering medication 

• Prevent ADRs 

• Use appropriate adjuvant analgesic and non-drug therapies 

Cancer Pain Management

• Oral route

• is preferred when available 

• Choose the analgesic drug and dose to

• match the degree of pain suffered by the patient 

Pain medication should always be administered on

a schedule and not on PRN basis 

persistent severe pain,

• use an analgesic with long duration of action to minimize frequency of administering medication 

• Prevent ADRs 

Use appropriate

adjuvant analgesic and non-drug therapies 

Mild Pain (rated 1 to 3)

• Treated with non-opioid medications (i.e. NSAIDs, Paracetamol)

Mild to Moderate Pain (rated 4 to 6)

• Treated with weak opioids (e.g. Tramadol) with or without NSAIDs and Paracetamol

• Reassess pain and use rescue medication for breakthrough pain

Moderate to Severe Pain (rated 7 to 10)

• Persistent pain

• Treat with strong opioids (e.g. morphine, fentanyl citrate) with or without NSAIDs and Paracetamol

Moderate to Severe Pain (rated 7 to 10)

• If still not working

• = increase opioid dose until “end of dose failure “ unless S/E develop

Moderate to Severe Pain (rated 7 to 10)

• If S/E develop,

• switch opioid or route of admin; use an equivalent analgesic dose (if you switched opiods)

Moderate to Severe Pain (rated 7 to 10)

• If pain persists,

• reassess pain and treatment and consider invasive intervention

Analgesic Medications

Non-Opioid Analgesic

Opioid Analgesic

Non-Opioid – Opioid Combination

Non-Opioid Analgesic

Act peripherally to inhibit the activity of prostaglandin in the pathway

Opioid Analgesic

Act centrally in the brain and at the level of the spinal cord at specific opioid receptor

Adjuvant Therapy

Antidepressant (Amitriptyline) and Anticonvulsant

Transdermal Lidocaine

Corticosteroid

Benzodiazepine, Diazepam and Lorazepam

Antidepressant (Amitriptyline) and Anticonvulsant

neuropathic pain

Transdermal Lidocaine

localized neuropathic pain

Corticosteroid

inflammation, bone pain, or increased intracranial pressure

Benzodiazepine, Diazepam and Lorazepam

muscle pain or muscle spasms

Chemotherapy-induced N&V

• is one of the most common and distressing acute side effects of cancer treatment '

•  It occurs in up to 80% of patients 

N&V can also result in the following:

• Serious metabolic derangements. 

• Nutritional depletion and anorexia. 

• Deterioration of the patient’s physical and mental status. 

• Esophageal tears. 

• Fractures. 

• Wound dehiscence. 

• Withdrawal from potentially useful and curative antineoplastic treatment. 

• Degeneration of self-care and functional ability. 

Nausea

• is the subjective experience of an unpleasant, wavelike sensation in the back of the throat and/or the epigastrium that may culminate in vomiting (emesis). 

• mediated through the autonomic nervous system.

Vomiting

• (emesis) is the forceful expulsion of the stomach, duodenum, or jejunum through the oral cavity. 

• stimulation of a complex reflex that includes convergence of afferent stimulation

Factors related to the tumor, treatment, and patient all contribute to N&V,

including tumor location, chemotherapy agents used, and radiation exposure. 

n&v Patient-related factors may include the following:

• Incidence and severity of N&V during past courses of chemotherapy. Patients with poor control of N&V during past chemotherapy cycles are likely to experience N&V in subsequent cycles. 

• History of chronic alcohol use. Patients with a history of chronic high intake of alcohol are less likely to experience cisplatin-induced N&V. 

• Age. N&V is more likely to occur in patients younger than 50 years. 

• Gender. N&V is more likely to occur in women. 

• History of morning sickness or emesis during pregnancy

Acute N&V

N&V experienced during the first 24 hours after chemotherapy administration.

Delayed (or late) N&V

N&V that occurs more than 24 hours after chemotherapy administration

Anticipatory N&V (ANV)

N&V that occurs before a new cycle of chemotherapy in response to conditioned stimuli such as the smells, sights, and sounds of the treatment room.

Breakthrough N&V

Vomiting that occurs within 5 days of prophylactic use of antiemetics and requires rescue.

Refractory N&V

N&V that does not respond to treatment.

Chronic N&V in patients with advanced cancer

N&V is associated with a variety of potential etiologies

Risk Factors and Risk Assessment

• Patient’s age (younger patients or younger than 50 years old) 

• Female 

• History of Morning Sickness

• History of Nausea and Vomiting in previous chemotherapy 

• History of Alcoholism

High

• AC combination defined as either doxorubicin or epirubicin with cyclophosphamide

• Carboplatin (greater than or equal to AUC of 4)

• Cisplatin

• Cyclophosphamide (greater than 1,500 mg/m²)

• Doxorubicin (greater 50 mg/m²)

Moderate

• Carboplatin (less than AUC of 4)

• Cyclophosphamide (less than or equal to 1,500 mg/m²)

• Doxorubicin (less than or equal to 50 mg/m²)

• Methotrexate (greater than or equal to 250 mg/m²) 

Low

• Doxorubicin (liposomal)

• 5-Fluorouracil (5-FU)

• Methotrexate (greater than 50 mg/m² but less than 250 mg/m²)

• Paclitaxel

Minimal

• Methotrexate (less than or equal to 50 mg/m²)

• Vinblastine

• Vincristine

SEROTONIN (5HT3) RECEPTOR ANTAGONISTS

ondansetron

granisetron

dolasetron

palonosetron

Serotonin released from the gut in response to various stimuli acts on

the chemoreceptor trigger zone (CTZ) in the brainstem, initiating the vomiting reflex 

SEROTONIN (5HT3) RECEPTOR ANTAGONISTS
moa

• Blocks serotonin receptor peripherally in the gastrointestinal tract and centrally in the medulla 

SEROTONIN (5HT3) RECEPTOR ANTAGONISTS
most effective when

given in conjunction with steroids 

SEROTONIN (5HT3) RECEPTOR ANTAGONISTS
Major side effects of this class of medications include

mild headache and constipation.

ondansetron

(oral) is given 3 times daily, starting 30 minutes before chemotherapy and continuing for up to 2 days after chemotherapy is completed

granisetron

is approved for use without dosage modification in patients older than 2 years, including elderly patients and patients with hepatic and renal insufficiency

dolasetron

(oral) may be dosed as 100 mg within 1 hour before chemotherapy

palonosetron

It has a higher potency, a significantly longer half-life (approximately 40 hours)

NK-1 RECEPTOR ANTAGONISTS (SUBSTANCE P ANTAGONISTS

• In combination with a 5-HT3 receptor antagonist and a corticosteroid, NK-1 receptor antagonists are indicated for

• the prevention of acute and delayed N&V 

• NK-1 RECEPTOR ANTAGONISTS (SUBSTANCE P ANTAGONISTS
  examples

Aprepitant and fosaprepitant

Netupitant and fosnetupitant

Rolapitant

• Aprepitant

• is efficacious in preventing N&V in breast cancer patients receiving highly emetogenic chemotherapy with cyclophosphamide and doxorubicin 

• Fosaprepitant

• is approved as a single dose of 150 mg before chemotherapy on day 1 

Netupitant and fosnetupitant

marketed as either an oral fixed-combination product containing 300 mg of netupitant and 0.5 mg of palonosetron (NEPA) or an IV fixed-combination product containing 235 mg of fosnetupitant and 0.25 mg of palonosetron

Rolapitant

does not affect cytochrome P450 3A4 enzymes; therefore, no dose adjustment for dexamethasone is required.

CORTICOSTEROIDS

• MOA:

• Unknown, thought to act by inhibiting prostaglandin synthesis in the cortex 

Steroids

• quantitatively decrease or eliminate episodes of N&V and may improve patients’ mood 

• given orally or intravenously before chemotherapy and may be repeated 

• CORTICOSTEROIDS
  examples

Dexamethasone

Methylprednisolone

Dexamethasone

often the treatment of choice for N&V in patients receiving radiation to the brain, as it also reduces cerebral edema

Methylprednisolone

also administered orally or intravenously at doses and schedules that vary from 40 mg to 500 mg every 6 to 12 hours for up to 20 doses

 BENZAMIDE ANALOGS

• Blocks dopamine receptor in the CTZ 

• Stimulation of cholinergic activity in the gut 

• Increasing gut motility 

• Antagonizes peripheral serotonin receptor in the intestine

 BENZAMIDE ANALOGS
examples

• Prochlorperazine, Chlorpromazine, Promethazine 

SUBSTITUTED BENZAMIDES
example

Metoclopramide

Metoclopramide is most effective against

• acute vomiting when given IV at high doses 

Metoclopramide has also been safely given by

IV bolus injection at higher single doses (up to 6 mg/kg) and by continuous IV infusion, with or without a loading bolus dose

BUTYROPHENONE

• Similar to and as effective as phenothiazine 

Phenothiazine

– antipsychotic medication with antiemetic effects to treat transient nausea and vomiting associated with viral infections, surgery or gastrointestinal illnesses 

• Benzodiazepines, such as lorazepam and alprazolam,

• are valuable adjuncts in the prevention and treatment of anxiety and the symptoms of anticipatory N&V 

• have not demonstrated intrinsic antiemetic activity as single agents, so they are adjuncts to other antiemetic agents in antiemetic prophylaxis and treatment 

OLANZAPINE’s activity at multiple receptors

• particularly at the D2 and 5-HT3 receptors that appear to be involved in N&V, suggests that it may have significant antiemetic properties 

The addition of olanzapine to

azasetron and dexamethasone improved the CR of delayed CINV

Cannabinoid receptor in the brain and gut

may mediate at least some of the antiemetic activity 

CANNABINOID

• Inhibition of prostaglandin and blockade of adrenergic 

• Heavy and long-term cannabinoid use can lead to Cannabinoid Hyperemesis Syndrome characterized with cyclic vomiting or repeated episodes of severe N&V