Download - Jamilah Alsaidan, Msc. The three consecutive phases of emesis are: Emesis NauseaRetchingVomiting

Chemotherapy Induced Nausea and VomitingJamilah Alsaidan, Msc

The three consecutive phases of emesis are:

Chemotherapy Induced Nausea and Vomiting

Emesis

Nausea Retching Vomiting

• Inclination to vomit• Feeling in throat or epigastric region alerting

individual vomiting is imminent. Nausea

• Is the labored movement of the abdominal and thoracic muscles before vomitingRetching

• The forceful expulsion of gastric contents through the mouth due to GI retroperistalsisVomiting


Vomiting is triggered by afferent impulses to the vomiting center, a nucleus of cells in the medulla

Impulses are received from sensory centers, such as:

the chemoreceptor trigger zone (CTZ), Cerebral cortex, visceral afferents from the pharynx and GI

tract

Chemotherapy Induced Nausea and Vomiting- Etiology

Numerous neurotransmitter receptors are located in the vomiting center, CTZ, and GI tract

Cholinergic, histaminic, dopaminergic, opiate, serotonergic, neurokinin, and benzodiazepine receptors

Three main causes of vomiting Stimulation of chemoreceptor trigger zone

in the 4th ventricle Stimulation of the GI tract Sensory input and memory

Chemotherapy Induced Nausea and Vomiting- Etiology

Nausea and or / vomiting may be part of the symptom complex for a variety of gastrointestinal, cardiovascular, infectious, neurologic, metabolic or psychogenic processes


N & V may be a feature of such conditions as pregnancy, may follow operative procedures administration of certain medications such

as those used in cancer chemotherapy or inhalation of noxious odors


General Depending on severity of symptoms, patients

may present in mild to severe distress Symptoms Simple: Self-limiting, resolves spontaneously

and requires only symptomatic therapy Complex: Not relieved after administration of

antiemetics; progressive deterioration of patient secondary to fluid-electrolyte imbalances; usually associated with noxious agents or psychogenic events

Chemotherapy Induced Nausea and Vomiting- Clinical Presentation

Signs Simple: Patient complaint of queasiness or

discomfort Complex: Weight loss; fever; abdominal

pain Laboratory tests Simple: None Complex: Serum electrolyte concentrations;

upper/lower GI evaluation

Chemotherapy Induced Nausea and Vomiting- Clinical Presentation

Chemotherapy Induced Nausea and Vomiting- Clinical Presentation Other information Fluid input and output Medication history Recent history of behavioral or visual

changes, headache, pain, or stress Family history positive for psychogenic

vomiting

Gastrointestinal mechanisms Mechanical obstruction- e.g. Gastric outlet

obstruction, Small bowel obstruction Functional gastrointestinal disorders-

e.g.Gastroparesis, Nonulcer dyspepsia, Chronic intestinal pseudoobstruction, Irritable bowel syndrome

Organic gastrointestinal disorders e.g Peptic ulcer disease,Pancreatitis, Pyelonephritis, Cholecystitis ,Cholangitis, Hepatitis

Acute gastroenteritis ( Viral, Bacterial)

Chemotherapy Induced Nausea and Vomiting- Specific etiologies

Cardiovascular diseases Acute myocardial infarction

Miscellaneous causes Pregnancy Noxious odors Operative procedures

Neurologic processes Migraine headache Vestibular disorders

Chemotherapy Induced Nausea and Vomiting- Specific etiologies

Chemotherapy Induced Nausea and Vomiting- Specific etiologies Metabolic disorders Diabetes mellitus

(diabetic ketoacidosis) Renal disease

(uremia) Psychiatric causes Anxiety disorders Anorexia nervosa Drug withdrawal Opiates Benzodiazepines

Therapy-induced causes

Cytotoxic chemotherapy

Radiation therapy Anticonvulsant

preparations Opiates Antibiotics

Emetogenic potential of chemotherapy agents

HighModerateLowMinimal

Chemotherapy Induced Nausea and Vomiting- Emetogenic potential of some cytotoxic agents

High (>90%) Carmustine Cisplatin Cyclophosphamide

≥1,500 mg/m2 Dacarbazine

Dactinomycin Mechlorethamine Streptozotocin

Moderate (30–90%) Carboplatin Cytarabine >1 g/m2

Cyclophosphamide <1,500 mg/m2 Daunorubicin

Doxorubicin Epirubicin Idarubicin Ifosfamide Irinotecan Oxaliplatin

Chemotherapy Induced Nausea and Vomiting- Emetogenic potential of some cytotoxic agents

Low (10–30%) Bortezomib Cetuximab Cytarabine ≤1 g/m2 Docetaxel Etoposide Fluorouracil Gemcitabine Methotrexate Mitomycin Mitoxantrone Paclitaxel Pemetrexed Topotecan Trastuzumab

Minimal (<10%) Bevacizumab Bleomycin Busulfan 2-Chlorodeoxyadenosine

Fludarabine Rituximab Vinblastine Vincristine Vinorelbine

Non-Chemotherapy Etiologies of Nausea and vomiting in cancer patients

Fluid and electrolyte abnormalities Hypercalcemia Volume depletion Adrenocortical insufficiency Drug Induced Opiates Antifungals Antibiotics


Other Uremia Metastases Gastrointestinal obstruction Increased intracranial pressure Peritonitis Radiation Therapy


The overall goal of antiemetic therapy is to prevent or eliminate nausea and vomiting

This should be accomplished without adverse events or with clinically acceptable adverse effects

Simple nausea and vomiting prevention is achieved easily with treatment

Patients with more complex problems require greater assistance

Chemotherapy Induced Nausea and Vomiting- Desired outcome of treatment

General Approach to Treatment

Non drug Modalities Medication

Chemotherapy Induced Nausea and Vomiting- Treatment Modalities

The treatment choice depends on severity of the NV and associated conditions

The management of psychogenic vomiting is greatly dependent on psychological intervention

Underlying problems are complex and must be addressed

Treatment of underlying psychological disorder with its appropriate medications

E.g. Bulimia nervosa


Non drug modalities include Dietary, Psychological, or physical changes

Simple complaints- Avoid or intake in moderation troublesome food, beverage or odor

Behavioral interventions include relaxation, biofeedback, self hypnosis, cognitive distraction, guided imagery, and systematic desensitization

Chemotherapy Induced Nausea and Vomiting- Non Drug Modalities

Antiemetic drugs- both non-prescription and prescription are recommended

The treatment of simple nausea and vomiting usually requires minimal therapy. Drugs are usually effective in small, infrequently administered doses.

The management of complex nausea and vomiting, for example, in patients who are receiving cytotoxic chemotherapy, may require combination therapy.

Chemotherapy Induced Nausea and Vomiting- Pharmacologic Therapy

Many treatment options for clinician to choose from

Factors that enable a clinician to discriminate between medication options:

A) The suspected etiology of the symptoms B) The frequency, duration, and severity of the

episodes C) The ability of the patient to use oral, rectal,

injectable, or transdermal medications D) The success of previous antiemetic

medication


In relation to chemotherapy administration; Nausea or vomiting that occurs:

within 24 hours: Acute Intensity peaks after 5-6 hours after 24 hours: Delayed before chemo given: Anticipatory


The distinction between acute and delayed symptoms becomes blurred with respect to time of onset after several doses and for several consecutive days

Delayed symptoms are best described with cisplatin


Breakthrough vomiting occurs despite prophylactic treatment and /or requires additional rescue medications

Refractory emesis refers to emesis that occurs during treatment cycles when antiemetic prophylaxis and / or rescue therapy has failed in previous cycles


Factors to consider when selecting an antiemetic for CINV include the following:

1) The emetic risk of the chemotherapy agent or regimen

2) Patient specific factors3) Patterns of emesis after administration of

specific chemotherapy agents or regimens

Chemotherapy Induced Nausea and Vomiting- Factors to consider

The emetic risk of the agent is the most important and primary factor to consider when deciding IF you will administer prophylactic agents and WHICH antiemetic agent to select

The combination of metoclopramide and dexamethasone was the most common regimen to prevent delayed nausea and vomiting before the availability of aprepitant

The combination is still used when aprepitant has not been incorporated into the initial regimen for CINV

Single agent phenothiazaine butytophenone, or steroids are used for mildly to moderately emetogenic regimens and for “as needed” use for prolonged symptoms ( breakthrough symptoms)

Chemotherapy Induced Nausea and Vomiting- Factors to consider

Patients receiving chemotherapy classified to be high risk should receive a combination antiemetic regimen containing three drugs on the day of chemotherapy administration (Day one)

A serotonin 5-HT3 inhibitor (e.g. Dolasetron, Granisetron, Ondansetron, Palonosetron, ) + dexamethasone plus NK1 inhibitor ( e.g. aprepitant)


Patients receiving regimens that are classified as being of moderate emetic risk should receive a combination antiemetic regimen containing an serotonin 5-HT3 inhibitor plus dexamethasone on day 1.

The exception to this is patients receiving an anthracycline and cyclophosphamide should receive the triple regimen described for high emetic risk regimens

For prophylaxis prior to administration of regimens classified as low emetogenic risk dexamethasone alone is recommended


High Emetic risk Serotonin 5-HT3 inhibitor + dexamethasone +

aprepitantModerate Emetic risk Anthracycline + cyclophosphamide:Serotonin 5-HT3 inhibitor + dexamethasone + aprepitant All other regimens of moderate emetic risk:Serotonin 5-HT3 inhibitor + dexamethasone

Low Emetic Risk DexamethasoneMinimal riskNo medication

Chemotherapy Induced Nausea and Vomiting- Prophylaxis of Acute Phase of CINV on Day of Chemotherapy Administration (Day 1)

High Emetic Risk Serotonin 5-HT3 inhibitor : Dolasetron 100 mg po or 100 mg IV or 1.8

mg/kg IV Granisetron 2 mg po or 1 mg IV or 0.01 mg/kg

IV Ondansetron 24 mg po or 8 mg IV or 0.15

mg/kg IV Palonosetron 0.25 mg IV AND Dexamethasone 12 mg po AND Aprepitant 125 mg po

Chemotherapy Induced Nausea and Vomiting- Prophylaxis of Acute Phase of CINV on Day of Chemotherapy Administration (Day 1) DOSES

Moderate emetic risk Anthracycline and cyclophosphamide- as before,

as high emetic risk All other regimens of moderate emetic risk: Dolasetron 100 mg po or 100 mg IV or 1.8

mg/kg IV Granisetron 2 mg po or 1 mg IV or 0.01 mg/kg IV Ondansetron 24 mg po or 8 mg IV or 0.15 mg/kg

IV Palonosetron 0.25 mg IV AND Dexamethasone 8mg IV


Low Risk Dexamethasone 8mg IV

Minimal Risk None


High Emetic Risk Days 2 and 3 after chemotherapy: dexamethasone (8mg

IV) + aprepitant (80mg PO)Moderate Emetic risk Anthracycline + cyclophosphamide:Days 2 and 3 after chemotherapy: aprepitant ( 80mg

PO) All other regimens of moderate emetic risk:Days 2–4 after chemotherapy: dexamethasone 8mg PO

daily or Serotonin 5-HT3 inhibitor

Ondansetron 8mg PO daily or twice dailyGranisetron 1mg PO dailyDolasetron 100mg PO daily

Chemotherapy Induced Nausea and Vomiting- Prophylaxis of Delayed Phase of CINV

Low Emetic Risk- None

Minimal Emetic Risk- None

Chemotherapy Induced Nausea and Vomiting- Prophylaxis of Delayed Phase of CINV

The best strategy to prevent delayed CINV is to control acute CINV

Aprepitant, dexamethasone and metoclopramide have demonstrated efficacy in preventing delayed CINV

Patients receiving cisplatin and other agents are at highest risk to experience delayed NV

The management of delayed CINV caused by high risk emetogenic regimens is more well defined than moderate emetic risk regimens


Cannabinoids are used after the failure of other regimens or to stimulate appetite

Consider using an H2 blocker or proton pump inhibitor to prevent dyspepsia ( may mimic nausea)

Not FDA approved indications therefore doses not recommended


Download - Jamilah Alsaidan, Msc. The three consecutive phases of emesis are: Emesis NauseaRetchingVomiting

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