Cancer and nausea

Did You Know?

• Errors in patients' memories can influence their PROs compared to if they had been asked while experiencing nausea rather than afterwards.
• In 2008, 12.7 million new cancer cases and 7.6 million cancer deaths were estimated worldwide.

Causes

Medical conditions arising from cancer or its treatment that carry a high risk of nausea or vomiting include malignant bowel obstruction (MBO), chemotherapy-induced nausea and vomiting (CINV), anticipatory nausea and vomiting (ANV), and radiotherapy-induced nausea and vomiting (RINV). Malignant bowel obstruction is a common complication of advanced cancer, particularly in colorectal, ovarian, breast cancer, and melanoma. Three percent of all advanced cancers lead to MBO, and 25 to 50 percent of ovarian cancer patients experience at least one episode. Mechanisms causing nausea in MBO include mechanical compression of the gut, motility disorders, secretion accumulation, decreased absorption, and inflammation. Bowel obstruction may also result from radiation therapy or post-surgical adhesions. Constipating drugs like opioids can slow peristalsis and cause functional obstruction. Chemotherapy-induced nausea and vomiting is classified as early onset (within 24 hours), delayed onset (24 hours to several days), or anticipatory (triggered by taste, odor, sight, thoughts, or anxiety).

Pathophysiology

Nausea and vomiting in cancer patients may have multiple causes, and more than one cause can stimulate symptoms via different pathways. The underlying cause may be disease-related or treatment-related, and in some cases the cause remains unknown. Emetic stimuli are received and processed in the brain, where loosely organized neuronal networks in the medulla oblongata coordinate the emetic reflex. Key brain stem nuclei include the parvicellular reticular formation, the Bötzinger complex, and the nucleus tractus solitarii. Efferent outputs from the brain include vagal efferents to the esophagus, stomach, and intestine, spinal somatomotor neurons to abdominal muscles, and phrenic motor neurons to the diaphragm. Autonomic efferents supply the heart, airways, salivary glands, and skin, producing prodromal signs such as salivation and pallor. Toxic substances in the gastrointestinal tract stimulate vagal afferent nerves in the gut mucosa, which communicate with the nucleus tractus solitarii and area postrema. Receptors involved include 5-hydroxytryptamine3 (5-HT3), neurokinin-1, and cholecystokinin-1. Local mediators from enterochromaffin cells, particularly 5-hydroxytryptamine, play a key role; this pathway is thought to underlie emesis induced by drugs like cisplatin.

Management

Management strategies depend on the underlying causes, whether they are reversible, the stage of illness, prognosis, and patient-specific factors. Anti-emetic drugs are chosen based on previous effectiveness and side effects. 5-HT3 antagonists block serotonin's effect on peripheral and central 5-HT3 receptors on vagal afferent nerve endings and the chemoreceptor trigger zone. They are effective for CINV, malignant bowel obstruction, and kidney failure with elevated serotonin levels. Examples include dolasetron, granisetron, ondansetron, palonosetron, and tropisetron, often used in combination for high-risk patients and recommended as the most effective prophylaxis for acute CINV. Corticosteroids like dexamethasone are used for chemotherapy-induced emesis, malignant bowel obstruction, raised intracranial pressure, and chronic nausea in advanced cancer, though their mode of action is unclear. NK1 receptor antagonists such as aprepitant block NK1 receptors in the brainstem and gastrointestinal tract; their antiemetic activity when added to a 5-HT3 antagonist plus dexamethasone has been shown in phase II studies. Cannabinoids are a useful adjunct in selected patients, offering weak antiemetic efficacy with sedation and euphoria, but their use is limited by toxic effects like dizziness, dysphoria, and hallucinations. They are an option for those intolerant or refractory to other agents.

Financial implications

Chemotherapy-induced nausea and vomiting imposes a heavy financial burden on cancer patients, with costs for prescription antiemetics averaging between $100 and $1400 per chemotherapy cycle depending on the drugs prescribed. These costs may discourage patients from seeking treatment or purchasing medication. For the healthcare system, general cancer symptom management accounts for 5% of annual hospital expenses. Patients receiving prophylactic antiemetic treatment pose a significantly lower burden on the system, while those without prophylaxis incur substantial costs from repeated hospital visits and emergency medication for uncontrolled CINV.