Olanzapine

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Olanzapine is an atypical antipsychotic antagonist of muscarinic, adrenergic, dopamine, and serotonin receptors. Clinical studies demonstrated that it improves prophylactic antiemetic regimens’ prevention of acute, delayed, and refractory or breakthrough CINV.3 As summarized below, olanzapine figures prominently in the updated 2017 ASCO guideline for antiemetics. However, it is important to note that olanzapine can lead to orthostatic hypotension and hyperglycemia and should not be administered to elderly patients with dementia-related psychosis.3

Cannabinoids

The FDA has approved the cannabinoids dronabinol and nabilone for treating refractory CINV. These agents are believed to antagonize the brain’s CB1 and CB2 receptors.3

The 2017 Updated ASCO Guideline                 

For adults undergoing chemotherapy regimens carrying a high emetic risk, such as cisplatin or cyclophosphamide plus an anthracycline, the updated 2017 ASCO guideline on antiemetics recommend adding olanzapine to standard combination antiemetic regimens, such as 5-HT3 receptor antagonist plus NK1 receptor antagonist plus dexamethasone.4 For adults undergoing carboplatin chemotherapy regimens or high-dose chemotherapy regimens, and for children receiving high-emetic-risk chemotherapies, the updated ASCO guideline recommends NK1 receptor antagonists plus 5-HT3 receptor antagonist plus dexamethasone.4

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The updated guideline notes that dexamethasone can be effective for patients receiving anthracycline plus cyclophosphamide chemotherapy when it is administered only on the day of chemotherapy; the authors therefore recommended that it be administered only on day 1 for these patients.4

For refractory or breakthrough treatment-related nausea and vomiting resistant to standard antiemetic regimens, the ASCO guideline authors recommended adding olanzapine to standard antiemetic regimens, or either dronabinol or nabilone cannabinoid as a rescue antiemetic therapy.4 However, they cautioned that the evidence base for cannabis (marijuana) is nascent and remains insufficient to justify a recommendation for its use to prevent or treat CINV.4

For low-emetic-risk radiotherapy, the updated guideline recommended rescue therapy alone, after RINV symptoms occur.4 For antiemetic prophylaxis against high-RINV-risk radiotherapy, such as among patients undergoing total body irradiation, the updated guideline recommended 5-HT3 receptor antagonist (ondansetron or granisetron, once to twice daily during radiation therapy, with the first dose administered prior to initiation of radiotherapy), and dexamethasone (4 mg oral or intravenous, once daily on days of radiation therapy, starting before radiotherapy).4 For moderate-RINV-risk radiotherapy, such as among patients undergoing upper abdominal or craniospinal irradiation, the updated guideline recommended prophylactic 5-HT3 receptor antagonist (ondansetron, granisetron, or tropisetron) and dexamethasone (4 mg oral or IV).4

References

  1. US National Cancer Institute (NCI). Treatment-Related Nausea and Vomiting (PDQ®)–Health Professional Version. https://www.cancer.gov/about-cancer/treatment/side-effects/nausea/nausea-hp-pdq
  2. Sommariva S, Pongiglione B, Tarricone R. Impact of chemotherapy-induced nausea and vomiting on health-related quality of life and resource utilization: a systematic review. Crit Rev Oncol Hematol. 2016;99:13-36.
  3. Rao KV, Faso A. Chemotherapy-induced nausea and vomiting: optimizing prevention and management. Am Health Drug Benefits. 2012;5(4):232–240.
  4. Hesketh PJ, Kris MG, Basch E, et al. Antiemetics: American Society of Clinical Oncology clinical practice guideline update. J of Clin Oncol. 2017;35(28):3240-3261. doi: 10.1200/JCO.2017.74.4789
  5. Molassiotis A, Burke TA, Dicato M, Gascon P, Roila F, Aapro M. Anticipatory nausea, risk factors, and its impact on chemotherapy-induced nausea and vomiting: results from the Pan European Emesis Registry Study. J Pain Sympt Manag. 2016;51(6):987-993.
  6. Kirkbride P, Bezjak A, Pater J, et al. Dexamethasone for the prophylaxis of radiation-induced emesis: a National Cancer Institute of Canada Clinical Trials Group phase III study. J Clin Oncol. 2000;18(9):1960-1966.
  7. US Department of Health and Human Services, National Institutes of Health, National Cancer Institute. Common terminology criteria for adverse events (CTCAE), Version 4.0. https://www.eortc.be/services/doc/ctc/CTCAE_4.03_2010-06-14_QuickReference_5x7.pdf