Nausea and Vomiting in the Oncology Patient

How to Cite This Chapter: Chan SWS, Goffin JR, Krzakowski M, Sacha T, Krzemieniecki K. Nausea and Vomiting in the Oncology Patient. McMaster Textbook of Internal Medicine. Kraków: Medycyna Praktyczna. https://empendium.com/mcmtextbook/chapter/B31.II.22.2.15. Accessed July 18, 2024.
Last Updated: September 17, 2021
Last Reviewed: September 17, 2021
Chapter Information

Chemotherapy-Induced Nausea and VomitingTop

Etiology and Pathogenesis

Nausea and vomiting are among the most feared adverse events in the treatment of oncology patients and may be associated either with treatment or with the disease itself. Chemotherapy-induced nausea and vomiting (CINV) must be minimized to preserve quality of life for patients undergoing chemotherapy. CINV can be divided, based on timing, into acute (occurring ≤24 h after administration of chemotherapy, typically within a few hours), delayed (occurring after 24 h and lasting 1-5 days), and anticipatory (a conditioned response from previous episodes of CINV).

Each chemotherapy agent can be subcategorized based on the emetogenic risk, where the percentage is based on the predicted probability of emesis without prophylaxis. Categories include high-risk agents (>90% probability of nausea and vomiting), moderate-risk agents (30%-90%), low-risk agents (10%-30%) and minimal-risk agents (<10%). Chemotherapy is often given as a combination of several agents and the emetogenic risk is determined by the most emetogenic of these. Examples of highly emetogenic agents include cisplatin as well as the combination of cyclophosphamide and an anthracycline. Targeted therapies and immune checkpoint inhibitors typically have low to minimal emetogenic risk and do not require prophylaxis.

Several areas in the central nervous system (CNS) and peripheral nervous system are implicated in the pathogenesis of CINV, including the chemoreceptor trigger zone and the vomiting center in the medulla, as well as the enteric nervous system in conjunction with vagal afferent and efferent pathways. The primary targets for antiemetics include 5-hydroxytryptamine (serotonin) receptors (5-HT3), neurokinin 1 (NK1) receptors, and dopamine receptors (D2).

Prevention and Treatment

Antiemetic prophylaxis is the cornerstone of preventing CINV in both the acute and delayed phases. Contemporary antiemetic regimens prevent nausea or the need for rescue medications in 80% of patients receiving a high-risk regimen.

Prophylactic Pharmacotherapy

Acute and delayed nausea and vomiting: The prophylactic regimen depends on the emetogenic risk of the specific therapy. 5-HT3 receptor antagonists (eg, ondansetron, palonosetron) are much less effective in the delayed phase and are therefore usually not used in this phase, with NK1 receptor antagonists (eg, aprepitant, netupitant, fosaprepitant) now filling this role. Typical doses of representative drugs are shown in the tables below. Actual dosing and duration depend on the drug combinations used and their local availability. The prophylactic regimen is usually started within 30 to 60 minutes prior to chemotherapy.

1. Highly emetogenic chemotherapy (HEC): Table 1.

2. Moderately emetogenic chemotherapy (MEC): Table 2.

3. Low emetogenic chemotherapy (LEC): Table 3.

4. Minimal emetogenic risk: No preventive antiemetics are typically required.

Breakthrough nausea and vomiting: If patients experience breakthrough nausea and vomiting (ie, have symptoms despite prophylaxis), ensure that contributing causes such as constipation (possibly from opiate use), metastases to the CNS, bowel obstruction, electrolyte disturbances (eg, hypercalcemia), and radiation-induced nausea are also addressed.

If nausea and vomiting are not well controlled with appropriately used prophylactic regimens, consider the addition of an antiemetic class that has not been used previously. The as needed antiemetic should be used as scheduled until symptoms resolve. Oral olanzapine (2.5 mg bid as needed) is a preferred agent if not used in the prophylactic regimen, and may be increased up to 10 mg per day if already used at a lower dose. Other medications can include dopamine antagonists (eg, oral prochlorperazine [10 mg every 4-6 h], oral metoclopramide [10 mg every 4-6 h], or oral haloperidol [start with 0.5-1 mg every 4-6 h]). Cannabinoids such as oral nabilone (1-2 mg bid, as needed) or dronabinol capsules (2.5-5 mg tid to qid) may be used if other agents are not successful. Caution should be used when combining sedating agents.

In subsequent cycles of treatment, prophylaxis with additional antiemetics is warranted, and NK1 receptor antagonists may be helpful. Alternative strategies also include adjusting the chemotherapy through dose reduction, switching agents, or changing the infusion strategy. If there is a suspected anticipatory emesis, a benzodiazepine such as oral lorazepam (0.5-1 mg 30-60 min prior to the triggering event) can be added. If the patient is experiencing significant dyspepsia, a proton pump inhibitor can also be used.

Nausea and Vomiting in the Palliative SettingTop

Etiology

Symptoms of chronic nausea and vomiting in patients with incurable cancer in the palliative setting can be common, ranging from 30% to 70%. The causes are multifactorial and can include:

1) CNS: Brain metastases, meningeal involvement, vestibular dysfunction.

2) Gastrointestinal system: Malignant bowel obstruction, paraneoplastic disorders, constipation, metastases.

3) Medications: Opioids, antibiotics, palliative chemotherapy, radiation to abdominal and pelvic regions.

4) Endocrine system: Adrenal insufficiency (most often from steroid withdrawal).

5) Electrolyte disturbances: Hypercalcemia, hyponatremia.

6) Infection.

7) Psychologic causes: Anxiety, depression.

Management

The identification of the contributing cause guides treatment decisions. There is a paucity of evidence to suggest an optimal regimen and it is not evident that an etiology-based use of antiemetics is superior to a rescue antidopaminergic agent. In cases where there is no obvious cause, oral or IV metoclopramide (10 mg every 4 h) is the most studied agent and has the potential advantage of parenteral administration. Although there is a lack of comparative data, alternatives to consider include oral or subcutaneous haloperidol (start with 0.5-1 mg every 6 h) and olanzapine (2.5-10 mg). Prolonged use of antidopaminergic agents (>3 months) increases the risk of extrapyramidal adverse effects.

For opioid-related toxicity, constipation and the direct emetogenic effect of opioids should be addressed. For nausea not related to constipation, consider opioid rotation, which is switching from one opioid or administration route to another to reduce adverse events with equianalgesic effect. If that is insufficient in controlling symptoms, the addition of metoclopramide can also be considered.

TablesTop

Table 13.3-1. HEF: Multiple/single IV chemotherapy sample regimen

Drug

Dosing on day 1 (the day of chemotherapy)

Dosing on subsequent days

Aprepitant 

or

Netupitant (in combination with palonosetron)

or

Fosaprepitant

125 mg PO in a single dose

 

300 mg + 0.5 mg PO in a single dose

 

150 mg IV in a single dose

80 mg PO daily (on days 2-3)

 

 

 

Ondansetron

or

Palonosetron

8 mg PO bid or 8 mg IV in a single dose

0.5 mg PO in a single dose

None recommended

 

 

Dexamethasone

12 mg PO or 10 mg IV in a single dose

8 mg PO or 10 mg IV until 2 days after the last dose of chemotherapy

Olanzapine

5 mg PO in a single dose

5 mg PO daily or 2.5 mg PO bid for days of chemotherapy and up to 2-3 days after chemotherapy

bid, twice a day; HEF, highly emetogenic chemotherapy; IV, intravenous; PO, oral.

 

Table 13.3-2. MEC: Multiple/single IV chemotherapy sample regimen

Drug

Dosing on day 1 (the day of chemotherapy)

Dosing on subsequent days

Ondansetron

Palonosetron

8 mg PO bid or 8 mg IV in a single dose

0.5 mg PO in a single dose

None recommended

Dexamethasone

8 mg PO or 10 mg IV

None recommended

bid, twice a day; IV, intravenous; MEC, moderately emetogenic chemotherapy; PO, oral.

Table 13.3-3. LEC: Single IV chemotherapy sample regimen

Drug

Dosing on day 1 (the day of chemotherapy)

Dosing on subsequent days

Dexamethasone

8 mg po or 10 mg IV

None recommended

IV, intravenous; LEC, low emetogenic chemotherapy; PO, oral.

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