Chemotherapy-induced nausea and vomiting (CINV) remains a major adverse effect of cancer chemotherapy, despite the availability of several antiemetic drug classes. Although not life-threatening, CINV has a major impact on a patient’s quality of life (QOL) and ranks high on the list of factors most feared by patients receiving chemotherapy. Additionally, symptoms from CINV can be severely debilitating and often result in patients refusing further courses of chemotherapy, which can minimize the likelihood of achieving optimal outcomes. “Failure to control acute nausea and vomiting on the first day of chemotherapy will increase the risk of nausea and vomiting on subsequent days and in subsequent cycles of chemotherapy,” says John W. Mucenski, PharmD. “The downstream economic effects of not adequately controlling CINV with the first course of chemotherapy cannot be underestimated. These include calls to the office, additional visits for intravenous (IV) hydration and antiemetics, and the potential for hospitalization.”
CINV is not always confined to the acute period. “Most patients at risk for CINV will be treated with IV antiemetics therapy initially, but will be discharged with oral medications, which are not always as effective as IV agents,” explains Dr. Mucenski. “In many cases, patients will develop delayed-onset CINV, in which nausea and vomiting occur more than 24 hours after chemotherapy administration and last for 5 to 7 days or even longer [Figure 1].”
Providers tend to underestimate the number of patients who suffer from delayed-onset CINV, which evidence suggests affects as many as 50% to 70% of patients and occurs more often than acute-onset CINV. This may occur in part since patients often do not report side effects they experience at home following chemotherapy treatments. This type of CINV can significantly reduce QOL, increase treatment costs, and greatly impair a patient’s ability to provide care to themselves or others once they have been discharged. “It’s imperative to control delayed-onset CINV before it starts and utilize therapies that will most effectively address this issue,” Dr. Mucenski says. “Physicians need to make efforts to become informed on proper prophylaxis against delayed-onset CINV and better protect their patients after they leave outpatient or inpatient settings.”
Analyzing Treatment Options
Current guidelines call for use of a 5-hydroxytryptamine (serotonin) type 3 (5-HT3) receptor antagonist in patients receiving moderately and highly emetogenic chemotherapy. The 5-HT3 receptor antagonists are now included in most regimens for antiemetic control, but there are pros and cons to consider when using different agents. All approved 5-HT3 receptor antagonists are approved to prevent acute CINV, but palonosetron has a distinct advantage over the other agents in this class because it has been approved by the FDA for the prevention of delayed CINV in addition to acute CINV. Palonosetron has been shown to provide significantly higher complete response rates when compared with ondansetron in both acute and delayed phases of CINV in moderately emetogenic chemotherapy recipients. The agent binds differently to 5-HT3 receptors and has a 40-hour half life.
In other studies, significantly more patients who received palonosetron were nausea-free on Days 3-5 following moderately emetogenic chemotherapy when compared with those who received ondansetron. In addition, palonosetron has been demonstrated to be noninferior to ondansetron in the acute phase of CINV for patients receiving highly emetogenic chemotherapy [Figure 2]. Studies have also shown that palonosetron yields significantly higher rates of complete response in delayed-onset CINV when compared with dolasetron.
Combination Therapy Yields Greater Benefits
Substance P, which is mediated through the neurokinin-1 (NK1) receptor, is another recently identified neurotransmitter with activity in CINV. Substance P is one of a group of peptides located throughout the central nervous system and found in the gastrointestinal tract along with 5-HT3 receptors. “Aprepitant is a substance P/NK1 receptor antagonist approved by the FDA for the prevention of acute and delayed CINV when used with a 5-HT3 antagonist and dexamethasone,” says Dr. Mucenski. “The development of novel agents has given patients more options for management and improved control of CINV.” Recent data indicate that the combination of palonosetron plus aprepitant and dexamethasone is highly effective in the prevention of both acute and delayed-onset CINV following a variety of moderately to highly emetogenic chemotherapy regimens. Complete responses—no emesis and no additional medication for nausea and vomiting—have been achieved in the vast majority of patients during both acute and delayed phases of CINV.
The prevention of CINV allows for significantly greater QOL for patients during and following treatment, and can help patients achieve a higher compliance rate with subsequent treatments for their cancer. This can optimize their chances to improve long-term outcomes. “When patients are undergoing chemotherapy associated with moderate-to-severe nausea and vomiting, clinicians should consider combining palonosetron with aprepitant plus dexamethasone to improve outcomes,” Dr. Mucenski says. “Furthermore, guidelines from the American Society of Clinical Oncology are expected soon. These will provide clinicians with evidence-based recommendations to further improve CINV prophylaxis.”
Readings & Resources (click to view)
Saito M, Tsukuda M. Review of palonosetron: emerging data distinguishing it as a novel 5-HT3 receptor antagonist for chemotherapy-induced nausea and vomiting. Expert Opin Pharmacother. 2010;11:1003-1014.
Kris MG, Hesketh PJ, Somerfield MR, et al. American Society of Clinical Oncology guideline for antiemetics in oncology: update 2006. J Clin Oncol. 2006;24:2932-2947.
Grunberg SM, Deuson RR, Mavros P, et al. Incidence of chemotherapy-induced nausea and emesis after modern antiemetics. Cancer. 2004;100:2261-2268.
Navari RM, Province PS. Emerging drugs for chemotherapy-induced emesis. Expert Opin Emerging Drugs. 2006;11:137-151.
Hajdenberg J, Grote T, Yee L, et al. Infusion of palonosetron plus dexamethasone for the prevention of chemotherapy-induced nausea and vomiting. J Support Oncol. 2006;4:467-471.
Rojas C, Stathis M, Thomas AG, et al. Palonosetron exhibits unique molecular interactions with the 5-HT3 receptor. Anesth Analg. 2008;107:469-478.