Cancer therapy, vomiting, and antiemetics.

Both radiotherapy and chemotherapy for cancer are capable of causing nausea and vomiting. With both treatment modalities, the nausea and vomiting is thought to be a second-order process rather than being due to direct stimulation of neuromechanisms that control vomiting. Both a peripheral (gastrointestinal tract) and central (chemoreceptor trigger zone) effect may be operating with both radiotherapy- and chemotherapy-induced vomiting. With radiotherapy, gastrointestinal toxicity is affected by the type of radiation, radiation dose and field size, fractionation schedule, individual patient factors, and the part of the patient that is radiated. Many different factors also influence the frequency and severity of nausea and vomiting following chemotherapy. With both radiotherapy and chemotherapy, the frequency and severity of nausea and vomiting is probably mediated by a reduction in breakdown of various neurotransmitters. It is presumed that as the levels of neurotransmitters increase, nausea and vomiting develop. Antagonists of these neurotransmitters may afford some antiemetic protection. Nausea and vomiting may be so severe in patients with cancer that they may refuse potentially curative therapy because of it. Anticipatory nausea and vomiting may develop in patients who have become quite sick after receiving treatment. Exposure to stimuli associated with the emetogenic agent is then sufficient to trigger nausea and vomiting. Standard antiemetics do not help anticipatory nausea and vomiting, although behavioural training may. A variety of different drugs have proven useful as antiemetics, including dopamine antagonists such as phenothiazines, metoclopramide, corticosteroids (dexamethasone and methylprednisolone), cannabinoids, and benzodiazapines. Antihistamines and anticholinergics are of value in some situations. New serotonin antagonists appear to be very promising and are currently undergoing clinical studies. Multiagent antiemetic regimens appear to be more effective than single agent regimens in some situations.