Development of Serotonin Antagonists for the Control of Chemotherapy‐Induced Emesis

Chemotherapy‐induced emesis is one of the most common and severe side effects of systemic cancer therapy. During the 1980s, the development of metoclopramide‐based combination antiemetic regimens resulted in complete or near‐complete control of emesis in 60–70% of patients receiving cisplatin‐based chemotherapy. However, 30–40% of patients remained poorly controlled with these regimens, and bothersome side effects such as extrapyramidal symptoms and sedation hindered therapy in some patients. The selective 5‐hydroxytryptamine (serotonin) inhibitors are a new class of antiemetics that have further improved the control of chemotherapy‐related nausea and vomiting. Ondansetron, the first of these compounds available commercially, has proven superior to high‐dose metoclopramide in controlling cisplatin‐induced emesis. In addition, no extrapyramidal side effects have been observed with ondansetron. Although the currently approved dosing schedule for ondansetron is 0.15 mg/kg intravenously (IV) every 4 hours for three doses, recent data indicate that a single 32 mg dose prior to chemotherapy may be superior. The addition of dexamethasone (10–20 mg IV prior to chemotherapy) improves the efficiency of ondansetron; this combination should be considered in all patients receiving cisplatin‐based chemotherapy. The role of ondansetron in non‐cisplatin chemotherapy is not completely defined, but patients unresponsive to other antiemetic therapy often have improved control with the addition of ondansetron.