Clinical Science Review: Comparative Review of 5-HT₃Receptor Antagonists in the Treatment of Acute Chemotherapy-Induced Nausea and Vomiting

Abstract

Since their introduction, 5-HT3 receptor antagonists have become the agents of choice in the prevention of acute chemotherapy-induced nausea and vomiting and are generally superior to high-dose metoclopramide regimens. The availability of four different agents (ondansetron, granisetron, dolasetron, and tropisetron) within this class has prompted investigations into potential differences between the drugs, which appear to be few. More importantly, the results of recently conducted randomized comparative trials in patients receiving moderately or highly emetogenic chemotherapy have demonstrated similar efficacy. Although study designs and patient populations differed, seven large comparative trials in patients receiving highly emetogenic chemotherapy reported no significant differences in complete or complete plus major response rates among the agents. Similar results were generally reported in trials evaluating patients receiving moderately emetogenic chemotherapy. The safety and tolerability of these agents also appear to be similar. The most common adverse events include headache, gastrointestinal effects, lightheadedness, and sedation. All agents are available in both intravenous and oral dosage forms and may be administered as a single dose.

Chemotherapy-Induced Nausea and Vomiting: The Importance of Acute Antiemetic Control

“…Chemotherapy-induced nausea and vomiting (CINV) are two of the greatest fears of patients with cancer [1][2][3][4]. Inadequately controlled CINV and radiation-induced nausea and vomiting (RINV) can precipitate a number of medical complications that may prove life threatening, including dehydration and electrolyte imbalance, or cause physical damage, including Mallory-Weiss tears of the esophagus.…”

“…The distressing symptoms of nausea and vomiting have a considerable impact on all aspects of the patients' qualities of life, as well as those of their family and caregivers. The distress resulting from these symptoms can escalate over time [5,6] and can potentially lead to a patient's refusal to continue with the most effective antitumor therapy [1,7,8]. Indeed, failure to control these side effects can lead to 25%-50% of patients delaying or refusing possible lifesaving antineoplastic therapy [9].…”

“…Acute nausea and vomiting are defined as occurring within 24 hours after chemotherapy and can be further subdivided into acute (within 12 hours) and late-acute (12-24 hours). Delayed nausea and vomiting are usually defined as commencing more than 24 hours after administration of chemotherapy and may persist for 6-7 days [1,10]. They…”

“…This specificity obviates the severe and distressing extrapyramidal side effects sometimes associated with conventional antiemetics [17]. The introduction of the 5-HT 3 -receptor antagonists has represented a significant clinical advance in the prevention of CINV, particularly for patients receiving highly emetogenic cisplatin-containing chemotherapy, in whom the 5-HT 3 -receptor antagonists generally produce superior efficacy to high-dose metoclopramide [1]. Three of these agents are licensed for use in the U.S.: granisetron, ondansetron, and dolasetron.…”

“…Anticipatory nausea and vomiting occur before, during, or after (but before acute chemotherapy symptoms would be expected to occur) the administration of a subsequent course of treatment if previous emetic control has been poor [10,11]. They are conditioned responses linked to visual, gustatory, olfactory, and environmental factors associated with previously administered chemotherapy [1]. Breakthrough nausea and vomiting refer to symptoms that occur despite antiemetic prophylaxis and/or necessitate the use of rescue medication.…”