Development of antiemetic therapy in cancer patients.

Patients still consider nausea and vomiting to be severe adverse consequences of cancer chemotherapy. The physiology of chemotherapy-induced nausea is generally unknown, but the finding that high doses of metoclopramide induce the antiemetic effect by antagonizing 5-HT3 receptors, has evoked increased interest in serotonin as a possible neurotransmitter. This has led to development of more selective 5-HT3 antagonists, such as ondansetron, granisetron and tropisetron, with improvement of antiemetic therapy, especially in patients receiving cisplatin-based chemotherapy. The efficacy of serotonin antagonists is further optimized by the addition of steroids and the dopamine D2 antagonist metopimazine. Many questions in antiemetic treatment are still unanswered and future trials should focus on patients receiving multiple-day chemotherapy or multiple cycles of chemotherapy and on patients resistant to initial antiemetic therapy.