Chemotherapy-Induced Nausea and Vomiting (CINV) is one of the most widely reported and distressing side effects for individuals undergoing cancer treatment. This adverse reaction can affect up to 80% of patients without proper preventive measures. CINV is a significant factor in a patient’s overall quality of life and their ability to adhere to the prescribed treatment schedule. Uncontrolled CINV can lead to serious physical complications, including dehydration, malnutrition, and electrolyte imbalances. Modern oncology focuses heavily on prophylaxis, or prevention, to mitigate these effects and ensure a smoother course of therapy.
Causes and Mechanisms
CINV involves complex processes in both the gastrointestinal tract and the central nervous system. Chemotherapy agents damage the rapidly dividing cells lining the gut, causing the release of chemicals, particularly serotonin. This serotonin binds to 5-HT\(_3\) receptors on vagal nerve fibers in the intestinal wall, transmitting a signal to the brainstem that initiates the emetic reflex.
A separate pathway involves the chemoreceptor trigger zone (CTZ), an area of the brain located outside the blood-brain barrier. Chemotherapy drugs activate receptors in the CTZ, which signals the nucleus tractus solitarius, often called the vomiting center. This central mechanism is mediated primarily by the neurotransmitter Substance P, which binds to neurokinin-1 (NK-1) receptors. The activation of both peripheral and central pathways coordinates the muscle contractions that result in vomiting.
The timing of CINV symptoms corresponds closely to these mechanisms. Serotonin release and 5-HT\(_3\) receptor activation are strongly associated with the immediate, or acute, phase of CINV. Conversely, the Substance P/NK-1 receptor mechanism is the primary driver of symptoms in the delayed phase. Understanding these distinct neurochemical pathways allows for a more targeted approach to antiemetic drug selection.
Classification and Risk Factors
CINV is classified into five distinct categories based on its timing relative to chemotherapy administration and the patient’s response to treatment.
Classification of CINV
- Acute CINV: Nausea or vomiting occurring within the first 24 hours following the infusion of the chemotherapy agent. Symptoms typically peak approximately five to six hours after treatment.
- Delayed CINV: Manifests more than 24 hours after treatment and can persist for up to five days.
- Anticipatory CINV: A conditioned response occurring before the patient even receives the drug, often triggered by sights or smells associated with prior chemotherapy sessions.
- Breakthrough CINV: Nausea or vomiting that occurs despite the patient receiving appropriate prophylactic antiemetic medications.
- Refractory CINV: CINV that continues to occur during subsequent cycles, even with changes to the antiemetic regimen.
The likelihood and severity of CINV depend on both the specific chemotherapy regimen and individual patient characteristics. The single most significant factor is the emetogenic potential of the chemotherapy drug, which is categorized into four risk levels: highly emetogenic (HEC, causing CINV in over 90% of patients without prophylaxis), moderately emetogenic (MEC, 30-90% risk), low, and minimal. The dose and route of administration also contribute to the risk.
Individual patient factors also play a substantial role in determining CINV risk. Female patients and those under the age of 55 are generally at a higher risk of experiencing CINV. A personal history of motion sickness, nausea and vomiting during pregnancy (hyperemesis gravidarum), or previous CINV episodes increases susceptibility. A history of chronic, heavy alcohol consumption is associated with a lower incidence of CINV.
Symptoms and Complications
The primary symptoms of CINV are nausea, an unpleasant feeling in the stomach, and emesis, the act of vomiting. Nausea is often reported to be the more distressing and prolonged symptom, sometimes persisting even when vomiting is controlled. Retching, a spasmodic contraction of the respiratory and abdominal muscles without the expulsion of stomach contents, can also occur.
Poorly controlled CINV leads to a cascade of complications that threaten the patient’s well-being and ability to continue cancer therapy. Significant fluid loss from repeated vomiting results in dehydration and serious electrolyte imbalances, such as low potassium or sodium levels. Persistent nausea causes a reduced appetite, leading to substantial weight loss, malnutrition, and physical deterioration.
In severe cases, the physical strain of violent vomiting can cause esophageal tears (Mallory-Weiss tears) or fractures in patients with underlying bone metastases. The psychological impact is also profound, contributing to anxiety, depression, and anticipatory nausea that can make future treatments more difficult.
Treatment and Management Strategies
The overarching goal in managing CINV is effective prophylaxis, meaning the prevention of symptoms before they start. Pharmacological treatment is tailored to the emetogenic risk of the chemotherapy regimen, with guidelines recommending a multi-drug approach for HEC and MEC. The standard of care for highly emetogenic chemotherapy involves a combination of three or four antiemetic agents.
Pharmacological Agents
The core antiemetic regimen includes several drug classes:
- 5-HT\(_3\) receptor antagonists (e.g., ondansetron): These primarily target the acute phase of CINV by blocking serotonin receptors in the gut and brain.
- Neurokinin-1 (NK-1) receptor antagonists (e.g., aprepitant): These block Substance P from binding to brain receptors, making them particularly effective against delayed CINV.
- Corticosteroids (e.g., dexamethasone): These are administered in combination and are thought to work through anti-inflammatory mechanisms.
For highly emetogenic chemotherapy, a four-drug regimen often includes the atypical antipsychotic olanzapine, which has shown enhanced efficacy for controlling nausea. Dopamine antagonists and cannabinoids, such as dronabinol, are typically reserved for treating breakthrough or refractory CINV. The specific combination and duration of antiemetics are carefully selected based on the patient’s risk factors and the chemotherapy agents being administered.
Non-Pharmacological Strategies
Non-pharmacological strategies serve as adjunctive therapies to complement the medication regimen. Behavioral therapies, such as systematic desensitization and guided imagery, can reduce the severity of anticipatory CINV. Dietary adjustments, such as eating small, bland meals and avoiding strong odors, also help manage symptoms. Evidence supports the use of ginger supplements and acupressure on the P6 point on the wrist as non-invasive methods to alleviate nausea.