Antiemetic Regimen Modification for Breakthrough Chemotherapy-Induced Nausea and Vomiting
Adding olanzapine 5 mg orally once daily on days 1-4 should be made to EP's prophylactic antiemetic regimen before her second cycle of dose-dense AC. 1
Background and Assessment
EP is a 56-year-old female who experienced uncontrolled nausea and vomiting during the first 3 days after her first cycle of dose-dense AC (doxorubicin and cyclophosphamide) for breast cancer, despite receiving appropriate prophylactic antiemetics:
- Fosaprepitant 150 mg IV (NK-1 antagonist)
- Ondansetron 16 mg orally (5-HT3 antagonist)
- Dexamethasone 12 mg orally on day 1 and 8 mg orally on days 2-4 (corticosteroid)
Rationale for Adding Olanzapine
The 2020 ASCO guidelines clearly state that for patients receiving an anthracycline combined with cyclophosphamide (which is classified as highly emetogenic chemotherapy), a 4-drug combination should be used:
- NK-1 receptor antagonist
- 5-HT3 receptor antagonist
- Dexamethasone
- Olanzapine 1
EP is currently receiving only 3 of these 4 recommended medications. The missing component is olanzapine, which should be added at a dose of 5 mg orally once daily on days 1-4.
Evidence Supporting Olanzapine Addition
The 2017 ASCO guidelines specifically recommend that "adult patients who experience nausea or vomiting despite optimal prophylaxis, and who did not receive olanzapine prophylactically, should be offered olanzapine in addition to continuing the standard antiemetic regimen." 1
A randomized, double-blind, placebo-controlled study by Komatsu et al. (cited in the 2017 ASCO guidelines) demonstrated that adding olanzapine to a standard antiemetic regimen significantly improved control of chemotherapy-induced nausea and vomiting. 1
Additionally, a 2019 randomized controlled trial showed that olanzapine 10 mg combined with ondansetron and dexamethasone was more effective than placebo in preventing CINV from doxorubicin plus cyclophosphamide in breast cancer patients, with particularly strong benefits in the first 24 hours after chemotherapy. 2
Why Other Options Are Not Optimal
Increasing ondansetron to 24 mg orally: There is no evidence supporting that increasing the dose of ondansetron beyond 16 mg provides additional benefit. The FDA-approved maximum single dose of ondansetron is 16 mg. 3
Adding prochlorperazine 10 mg orally every 6 hours: While dopamine antagonists like prochlorperazine can be used for breakthrough CINV, they are not recommended as first-line additions to prophylactic regimens that have failed. The guidelines specifically recommend olanzapine as the preferred agent to add when initial prophylaxis fails. 1
Changing ondansetron to palonosetron: While palonosetron is an effective 5-HT3 antagonist, the 2017 ASCO guidelines no longer specify palonosetron as the preferred 5-HT3 antagonist for moderately emetogenic chemotherapy. Additionally, simply switching between 5-HT3 antagonists is not the recommended approach when a patient has breakthrough CINV despite receiving a guideline-recommended regimen. 1
Implementation Recommendations
- Add olanzapine 5 mg orally once daily on days 1-4 to EP's antiemetic regimen
- Continue the current regimen of:
- Fosaprepitant 150 mg IV on day 1
- Ondansetron 16 mg orally on day 1
- Dexamethasone 12 mg orally on day 1 and 8 mg orally on days 2-4
Monitoring and Potential Side Effects
- Monitor for sedation, which is the most common side effect of olanzapine
- Advise the patient about potential somnolence, especially during the first 48 hours
- Consider administering olanzapine at bedtime to minimize daytime sedation
- Monitor for other potential side effects including dry mouth, increased appetite, and dizziness
Additional Considerations
If EP continues to experience breakthrough CINV despite the addition of olanzapine, a comprehensive reevaluation of her antiemetic regimen would be warranted, potentially considering:
- Lorazepam as an adjunctive medication
- Alternative NK-1 receptor antagonists
- Evaluation for other causes of nausea and vomiting