Chemotherapy-Induced Nausea and Vomiting
Uncontrolled CINV, a common side effect associated with cancer treatment, can negatively impact patient quality of life, delay treatment, and potentially cause physiologic consequences such as metabolic imbalances and esophageal tears. Fortunately, remarkable progress has been made in the CINV arena over the past several decades. Specifically, the introduction of serotonin receptor antagonists (eg, ondansetron, granisetron, dolasetron, palonosetron) and neurokinin-1 receptor antagonists (eg, aprepitant, fosaprepitant) have revolutionized the prevention and management of CINV. These agents are commonly used in combination with dexamethasone as prophylaxis for highly emetogenic chemotherapy.16
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With the exception of palonosetron, however, serotonin receptor antagonists are relatively ineffective for the prevention of delayed emesis.16 As a result, long-acting formulations of ondansetron (EUR-1025, Aptalis Pharmaceutical Technologies) and granisetron (APF530, AP Pharma) are currently under Phase 3 investigation for the prevention of CINV. Data indicate that 24mg of EUR-1025 administered orally once daily results in a similar rate and extent of drug exposure as 8mg of ondansetron dosed three times daily.17 In addition, a trial comparing APF530 with palonosetron for the treatment of acute and delayed CINV revealed that APF530 therapy was well-tolerated, and that its efficacy was non-inferior to that of palonosetron.18 Importantly, APF530’s single subcutaneous dosing offers increased convenience over palonosetron, which is administered intravenously. If approved, APF530 would be the only other serotonin receptor antagonist indicated for the prevention of both acute and delayed CINV.19
Neurokinin-1 receptor antagonists are frequently used for the prevention of delayed CINV, and rolapitant and netupitant are under investigation for use in patients receiving highly emetogenic chemotherapy. Rolapitant (Tesaro) has completed Phase 2 testing, which demonstrated 5-day CINV prevention following administration of a single dose of therapy.20 Netupitant (NKE, Helsinn/Roche), a potent and selective neurokinin-1 receptor antagonist, has recently commenced Phase 3 investigation for use in combination with palonosetron for the prevention of CINV.22 Data have shown that combined neurokinin-1 and serotonin receptor antagonist therapy is more effective in controlling acute and delayed CINV than serotonin antagonists alone, suggesting that a fixed-dose combination product may be a valuable therapeutic adjunct.21
