With 70% to 80% of patients who have cancer experiencing chemotherapy-induced nausea and vomiting (CINV), and reports of up to 40% of patients having anticipatory symptoms, the recent approval of a new anti-emetic called Akynzeo (netupitant/palonosetron) might be a welcome new supportive-care treatment for some patients.
The new medication could make a big difference in treating CINV, says Deborah L. Selm-Orr, an oncology nurse with Cancer Treatment Centers of America at Eastern Regional Medical Center in Philadelphia.
“Anticipatory CINV is when acute and delayed CINV were not adequately treated, and the patient then demonstrates a conditioned response [prior to additional treatment], much like Pavlov’s dogs,” she says. “So, it is best to treat CINV aggressively,” which could be possible because of the drug’s goal of preventing both acute and delayed CINV.
How Akynzeo Works
Akynzeo combines a standard anti-emetic, Aloxi (palonosetron) with a new drug called netupitant, which has been shown to prevent the side effect both immediately after chemotherapy and up to 3 days later (called the delayed phase of CINV).
The combination of the drugs helps prevent the side effect in two different ways.
“Our current understanding of pathways for nausea and vomiting includes at least 26 different chemical transmitters. At this time, we only have two distinct pathways that can be blocked: the NK1 pathway and the 5-HT3 pathway,” says Selm-Orr, who helped develop the CINV patient-care resources for the Oncology Nursing Society. “The new combination pill is a joining of blocking these two pathways.”
Specifically, Aloxi is a 5-HT3 receptor antagonist, which blocks the receptors in the brain and gut that trigger nausea and vomiting, while netupitant blocks the activation of the NK1 receptors in the central nervous system, preventing another signaling pathway involved in CINV.
Using a combination of anti-emetic drugs to tackle different pathways involved in CINV is a strategy that has been included in treatment guidelines, but Akynzeo is the first drug that combines two different types of therapies. Physicians have long been concerned about patients adhering to their anti-emetic therapy, and one goal is that this combination treatment improves adherence and, subsequently, patients’ quality of life.
The Food and Drug Administration based its approval of the supportive-care drug on two clinical trials that included a combined 1720 participants. Patients in the trial were randomly assigned to receive either the combination drug of Akynzeo or Aloxi alone.
In the first of the two trials, Aloxi prevented chemotherapy-induced vomiting in the acute phase (89.7%), delayed phase (80.1%), and overall (76.5%), but Akynzeo outperformed the standard in all phases with 98.5%, 90.4%, and 89.6% of patients, respectively, not reporting vomiting or nausea that needed rescue medication.
The oral drug should be taken 1 hour before each cycle of chemotherapy, along with the steroid dexamethasone. For patients receiving cisplatin chemotherapy, which carries a high risk of CINV, dexamethasone should be given once each on days 2 and 4. Common side effects reported with Akynzeo included headache, constipation, weakness, fatigue, and indigestion. There is also a rare risk of hypersensitivity, which can result in anaphylaxis.
In the Clinic