"It's the worst thing in the world—it's worse than my pain. I can't eat, nothing tastes good,
and I just don't feel like doing anything."
(AJ, a 52 year old woman with cholangiocarcinoma, experiencing constant pain and nausea
secondary to regional spread of tumor and gastroparesis secondary to radiation therapy.)
Nausea and vomiting (N&V) are complex and often multifactorial problems. Many cancer patients experience either or both during curative therapy or palliative cancer care. Nausea is more frequent, and may be the more significant problem because it is under-assessed and is more poorly controlled than vomiting. Nausea and vomiting are demoralizing, demeaning, and likely to negatively impact life quality (QOL) when either is severe or long-lasting, or interferes with important activities of daily living (ADLs), aggravates other toxicities of treatment (e.g., nephrotoxicity with cisplatin or bladder toxicity with cyclophosphamide secondary to inadequate fluid intake), or when associated with terminal illness.
Postchemotherapy nausea or vomiting can affect enjoyment of leisure activities, usual household tasks, eating and drinking, and spending time with family and friends.1–3 Despite antiemetic advances, patients still rank nausea as their most bothersome chemotherapy side effect, but rank vomiting lower.4,5 More than 75% of patients experience nausea, and about 40% vomit after chemotherapy despite receiving the best available antiemetics.3 Cancer patients may also experience N&V after radiation therapy and surgery, and 60% have nausea and 30% to 50% vomit because of progressive disease or other therapies.6,7
Because symptoms do not typically appear in isolation, nausea and vomiting often occur with each other, and within other symptom clusters, defined as three or more simultaneous symptoms that do not necessarily have the same cause. 8 Symptom clusters including nausea or vomiting vary and depend on disease and therapy factors, and other circumstances. For instance, patients who have advanced cancer or are receiving chemotherapy may concurrently have fatigue, anorexia, insomnia, pain, and dyspnea.3,9,10 Other symptoms can thus occur concomitantly but independently of N&V, or be a causative or resulting factor, and it is likely that distressing and uncontrolled symptoms or symptom clusters have negative effects on patient outcomes.
Chemotherapy, radiation therapy, other emetogenic drugs and therapies, another cancer-related condition or problem, or more than one of these may cause N&V. Chemotherapy can cause acute, delayed, and anticipatory chemotherapy-induced nausea and vomiting (CINV). Moderately to highly emetogenic agents are most likely to induce acute CINV, as well as delayed and persistent CINV. Anticipatory nausea is more common than anticipatory vomiting, and develops within three or four cycles of chemotherapy when CINV has been inadequately controlled—no matter how emetogenic the chemotherapy given.11,12 Anticipatory nausea and vomiting (ANV) occur by classical conditioning, as the events and cues surrounding chemotherapy (e.g., odors, tastes of drugs, visual cues such as the chemotherapy nurse) become linked with and can themselves induce subsequent acute and delayed CINV.3 There are no effective antiemetics for ANV, and more than 50% of patients who developed ANV may have moderate distress and/or nausea in response to odors (smell of the hospital or treatment area, foods or beverages consumed in the treatment area, chemical smells, and personal products such as perfume and shampoo), sights (hospital or treatment center, other patients with cancer, needles, foods and beverages that had evoked nausea or distress during chemotherapy), and tastes evocative of chemotherapy that persist for many years after chemotherapy completion.11 Persistent nausea or distress is related more to the control of CINV than to the emetic potential of the chemotherapy given.
Radiation therapy (RT) is most likely to cause N&V when the treatment field includes the upper and mid abdomen, when a large volume of tissue is treated, or when a larger dose is administered. Thus total body irradiation (TBI) and hemibody RT to the upper body most predictably cause N&V. The risk for N&V is moderate with lower hemibody fields and mild for RT to other body sites.13,14
Nausea and vomiting (intermittent or constant) are common in terminally ill cancer patients (pain and dyspnea are more frequent), but intractable vomiting is infrequent and generally occurs only during the last few days of life.6 Nausea and vomiting of progressive cancer are often multicausal and thus mediated via more than one pathway.7,15 Nausea and vomiting are most likely with advanced cancers of the stomach or breast and mesothelioma, but can occur with virtually any malignancy. Nausea and vomiting of terminal illness are usually moderately or more severe, but some patients report horrible or unendurable N&V.6,16 In rare instances, patients with terminal gastrointestinal (GI) tract, colon or rectum, or female genitourinary tract cancers can experience unendurable N&V that can only be controlled with therapeutic sedation for intractable suffering.
The pathogenesis of N&V is not fully understood but emesis occurs by one or more of several different mechanisms. Most research has focused on acute vomiting from chemotherapy, and less is known about the pathogenesis of nausea, as well as about N&V from other causes. Nausea and vomiting are different entities and may exist along a continuum or may be mediated by different mechanisms. Vomiting is a highly conserved normal physiological reflex that is a protective mechanism to rid a human being or animal of poisons or toxic substances, whether orally ingested or intravenously administered.
The two phases of N&V are pre-ejection and ejection. Nausea, an unpleasant feeling of the need to vomit (feeling sick at one's stomach), occurs in the pre-ejection phase.17,18 Nausea involves the cerebral cortex and autonomic nervous system, and may be accompanied by anorexia, pallor, tachycardia, and cold sweat. With the onset of nausea, the stomach relaxes, and gastric acid secretion is inhibited. Then a single retrograde giant contraction (RGC) of the small intestine propels alkaline small bowel contents back into the stomach, which further decreases the acidity of stomach contents and confines ingested material to the stomach. Retching (dry heaves), the first ejection phase event, occurs when the RGC reaches the stomach.19 Ultimately, vomiting ensues when coordinated contractions of the abdomen and diaphragm compress stomach contents and force them up through the mouth and nose (throwing up).
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