Current Options and Prospects for Effective Antiemetic Treatment in an Effort to Increase Adherence of Oncological Patients to Chemotherapy
Chemotherapy-induced nausea and vomiting (CINV) is strongly associated with treatment in the minds of many oncology patients, and its occurrence is rated as one of the most dreaded and stressful complications. For most patients, adherence to recommendations for antiemetic prophylaxis can successfully prevent the occurrence of CINV. A review article published last year by an international team of authors in the journal Future Oncology provides an overview of the current spectrum of options in CINV prophylaxis, focusing on the first combined preparation in this indication, containing the active substances netupitant and palonosetron.
Pathophysiology of CINV
CINV is a multifactorial process involving several neurotransmitters, including serotonin, dopamine, and substance P. In its acute form (within 24 hours of chemotherapy administration), CINV is mediated by the binding of serotonin to 5-HT3 receptors in the gut. Delayed CINV, on the other hand, is mediated mainly by the binding of substance P to neurokinin NK1 receptors in the CNS, specifically in the area postrema and nucleus tractus solitarii. The varying pathophysiological basis of acute and delayed CINV thus requires an appropriate pharmacological approach.
Current Options for Pharmacological Prophylaxis of CINV
Optimal prophylaxis of CINV is crucial for the success of antitumor treatment and for maintaining patients' quality of life. Nausea and vomiting can lead patients with a history of CINV to interrupt or discontinue treatment, or to choose less aggressive and thus less effective treatment options.
Recent studies have shown that adequate management of chemotherapy side effects, including CINV prophylaxis, leads to improved quality of life for patients, prolongs the duration of antitumor therapy, and overall survival. Nausea and vomiting are part of the emetic reflex but can also occur in isolation. Current antiemetics can effectively control vomiting, but their effect on nausea is limited.
Three main drug groups have high therapeutic potential in CINV prophylaxis and treatment: setrons (5-HT3 receptor antagonists), neurokinin receptor NK1 antagonists, and glucocorticoids, especially dexamethasone. In specific cases, the effect of the atypical antipsychotic olanzapine can also be utilized.
First-generation setrons include ondansetron, dolasetron, granisetron, and tropisetron. However, a side effect of first-generation setrons is the prolongation of the QTc interval. The only representative of second-generation setrons, palonosetron, differs from first-generation products in its higher potency, longer half-life, and synergistic effect when administered with NK1 receptor antagonists. These properties underpin its effect in the prophylaxis of both acute and delayed CINV. Compared to first-generation setrons, palonosetron administration has shown significantly less QTc interval prolongation and a lower incidence of dizziness. The favorable safety profile of palonosetron could lead to higher patient adherence to antiemetic and subsequently antitumor therapy.
Combination of Netupitant/Palonosetron (NEPA)
NEPA is the first fixed combination of antiemetics, containing palonosetron and netupitant, a second-generation setron and a representative of NK1 receptor antagonists. In the Czech Republic, this combination is approved for the prevention of acute and delayed CINV in patients receiving highly emetogenic chemotherapy containing cisplatin and moderately emetogenic chemotherapy. NEPA is recommended to be administered orally about 60 minutes before the start of the chemotherapy application. The antiemetic effect persists up to 5 days after NEPA administration.
Summary and Conclusion
Choosing the most appropriate antiemetic treatment regimen enables effective CINV prevention and thus higher adherence to antitumor therapy. As a result, patients' quality of life improves, and overall survival is prolonged. The combined fixed preparation NEPA allows single administration on the day of chemotherapy for up to 5 days of prevention of both acute and delayed CINV. The favorable pharmacokinetic profile of the NEPA combination, allowing the administration of both components orally in a single tablet, simplifies the management of CINV and could lead to the optimization of antiemetic treatment for oncological patients, and consequently to their higher adherence to chemotherapy.
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Sources:
1. Aapro M., Zhang L., Yennu S. Preventing chemotherapy-induced nausea and vomiting with netupitant/palonosetron, the first fixed combination antiemetic: current and future perspective. Future Oncol 2019; 15 (10): 1067–1084, doi: 10.2217/fon-2018-0872.
2. SPC Akynzeo. Available at: www.ema.europa.eu/en/documents/product-information/akynzeo-epar-product-information_cs.pdf
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