Bergsbaken: Chemotherapy-induced Nausea and Vomiting

Name treatment and patient-related risk factors for chemotherapy-induced nausea and vomiting

• Younger age

• Female

• Prior anticancer agents

• History of little or no alcohol use

• HIstory of morning sickness

• History of prone to motion sickness

• Anxiety

Name 5 chemotherapy drugs that are considered highly emetogenic at typical doses.

• Carboplatin (AUC >24)

• An Anthracycline + Cyclophosphamide

• Cisplatin

• Cyclophosphamide (>1500 mg/m2)

• Doxorubicin (>60 mg/m2)

*he won't test on cut offs

In global terms, describe the emetogenic risk of most oral, targeted agents.

Define acute vs delayed N/V, anticipatory N/V, and breakthrough N/V

What is the difference between a regimen that is considered highly-emetogenic vs moderately emetogenic?

• Go with whatever the highest risk drug is

What four drugs or drug classes are employed in current prophylaxis regimens for nausea & vomiting for high-emetic risk chemotherapy.

What is the maximum daily dose of ondansetron? How about the max single IV dose of ondansetron?

• Max daily dose = 24 mg

• Max single IV dose = 16 mg

What antiemetic prophylaxis regimen is typical for patients receiving chemotherapy with Minimal risk for nausea & vomiting? Low risk for nausea & vomiting?

What antiemetic prophylaxis regimen is typical for patients receiving chemotherapy with Moderate risk for nausea & vomiting?

What antiemetic prophylaxis regimen is typical for patients receiving chemotherapy with High risk for nausea & vomiting?

• 4 drug regimen!!

  • acute (day 1)

    • Olanzapine

    • NK1 antagonists **

    • 5HT3 R-antagonists

    • Dexamethasone

  • delayed (days 2-4)

• olanzapine

• dexamethasone

• **If aprepitant PO is used in the acute stage, must continue days 2+3 dosing

How should patients experiencing breakthrough nausea & vomiting be treated?

• Ondansetron or prochlorperazine

• Add one drug in a different class and continue standard antiemtic regimen

  • Olanzapine

  • Dronabinol

  • halo/metclo/scopola

  • prochlorperazine/promethazine

  • 5HT3 antag

  • Dexamethasone

  • Lorazepam(anticipatory only) 

How long should CINV prophylaxis continue for patients receiving regimens that are:

Only listed the NCCN preferred options, there are other treatment options

Moderately emetogenic

• 3 days 

  • Day 1 (2 drug regimen): 5HT3 RA + dexamethasone

  • Days 2-3: dexamethasone OR 5HT3 RA monotherapy 

Highly emetogenic

• 4 days 

  • Day 1 (4 drug regimen): Olanzapine + NK1 RA + 5-HT3 RA + Dexamethasone

  • Day 2-4: 

    • Olanzapine + Dexamethasone +/- Aprepitant on days 2 & 3 IF NK1-RA used on day 1

What are the major differences in the pharmacology and routes of administration of the HT3R antagonists?

• Ondansetron (1st generation)

  • Very effective for preventing acute CINV, but less for delayed CINV

  • PO,IV

• Granisetron (1st generation)

  • Very effective for preventing acute CINV, but less for delayed CINV

  • PO, transdermal patch, IV, SQ

• Palonosetron (2nd generation)

  • IV administration or PO in combination w/ netupitant 

  • 40 hour half-life

  • Effective for preventing acute and delayed CINV

Which one of the HT3R antagonists is least likely to cause prolongation of the QTc interval?

Palonosetron

What is the most common GI adverse effect of the HT3R antagonists?

• Ondansetron

  • Common: Headache and constipation 

  • Rare: QT prolongation & serotonin syndrome 

• Granisetron

  • Common: constipation & headache (less extend than ondansetron), Injection site reaction 

  • Rare: serotonin syndrome & QT prolongation (not associated with patch or SQ inj)

• Palonsetron

  • Side effects are uncommon 

  • Rare: serotonin syndrome

How do the doses of ondansetron differ for prophylaxis of patients receiving minimal/low, moderate, vs highly-emetogenic chemotherapy regimens?

• Minimal / low

  •  No routine prophylaxis recommended for minimal risk

  • Ondansetron 8-16 mg PO once for low risk 

• Moderate

  • Ondansetron 16-24 mg PO once or 8-16 IV once 

• Highly-emetogenic

  • Ondansetron 16-24 mg PO once or 8-16 IV once

What are the different formulations of the NK-1R antagonists, and how do their adverse effects differ?

• Aprepitant

  • PO (3 day course), IV emulsion (once)

  • Common SE: fatigue

• Fosaprepitant 

  • IV (once)

  • Common AE: injection site reaction

What drug interactions are expected with NK-1 R antagonists?

CYP3A4, CYP2C9

Fosaprepitant- infusion reactions

Design a prophylactic regimen for each CINV risk category (i.e., minimal, low, MEC, HEC).

Minimal

• No routine prophylaxis

Low

• Day 1: Dexamethasone OR metoclopramide OR prochlorperazine OR 5-HT3-RA

MEC

• Day 1 (2 drug regimen): 5HT3 RA + dexamethasone

• Days 2-3: dexamethasone OR 5HT3 RA monotherapy 

HEC

• Day 1 (4 drug regimen): Olanzapine + NK1 RA + 5-HT3 RA + Dexamethasone

• Day 2-4: 

  • Olanzapine + Dexamethasone +/- Aprepitant on days 2 & 3 IF NK1-RA used on day 1

How do the doses and frequency of dosing of olanzapine for CINV differ from its use as an atypical antipsychotic?

For CINV, olanzapine is typically given at 5–10 mg once daily for 3–4 days per chemotherapy cycle to prevent nausea and vomiting. In contrast, when used as an atypical antipsychotic, olanzapine is prescribed at 5–20 mg once daily for long-term treatment of conditions like schizophrenia or bipolar disorder.