Management of Adverse Effects

Nausea and Vomiting
Antiemetics prevent or relieve nausea and vomiting, which commonly occurs with radiotherapy to the abdomen and with many chemotherapeutic drugs, especially when given in combination. Sometimes the nausea and vomiting is functional or due to the cancer itself. Therefore, the underlying cause should always be sought and corrected.

Stimulation of the vomiting center in the medulla can arise in the chemoreceptor trigger zone (CTZ), cerebral cortex, or vestibular apparatus or can be relayed directly from peripheral areas (eg, gastric mucosa). Antiemetics appear to act in these areas, but their mechanism of action is not well understood. Generally, drug therapy is more successful for prophylaxis than for treatment of nausea and vomiting.

Serotonin-receptor antagonists are the most effective drugs available for the management of nausea and vomiting associated with radiotherapy or chemotherapy and with many disease processes. Virtually no toxicity occurs with granisetron and ondansetron, although headache and, rarely, orthostatic hypotension have occurred with ondansetron. These drugs are first-line antiemetic therapy; their major drawback is expense.

Antidopaminergics include many of the phenothiazines (eg, prochlorperazine, fluphenazine), which appear to act by selectively depressing the CTZ and, to a lesser extent, the vomiting center. These second-line drugs are useful in treating mild to moderate nausea and vomiting. Because most phenothiazines (except thioridazine and mesoridazine) appear to be equally effective if given in sufficient dosage, the choice of drug may depend on consideration of side effects.

Metoclopramide stimulates the motility of the upper GI tract, increases the tone and amplitude of gastric contractions, and increases duodenal and jejunal peristalsis. The result is accelerated gastric emptying and intestinal transit.

Metoclopramide functions as an antiemetic by its gastrokinetic effects and, in addition, appears to have some central dopamine antagonist actions. The most important side effects are extrapyramidal symptoms, which are in part dose-related. Benadryl will protect from these. Other side effects include drowsiness and fatigue. The drug is contraindicated when stimulation of GI motility might be dangerous (mechanical obstruction or perforation), in pheochromocytoma, and in epileptics or in patients receiving other drugs likely to cause extrapyramidal reactions. Its use as an antiemetic has largely been replaced by the serotonin-receptor antagonists.

Principles of Cancer Therapy