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.
Division of Oncology, Vanderbilt University, Nashville, Tennessee.
J D
JD
Hainsworth
D000932:Antiemetics / Q000008:administration & dosage / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects*; D004334:Drug Administration Schedule; D006801:Humans; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D014839:Vomiting / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology
D000932:Antiemetics; D000970:Antineoplastic Agents; D012702:Serotonin Antagonists