Chemotherapy-Induced Nausea and Vomiting - Pathophysiology, Risk Factors, and Treatment

Introduction

Nausea and vomiting are two common severe side effects of cancer chemotherapy that can adversely affect patients’ quality of life and their capability to endure and comply with treatment. Despite advancements in the control and treatment of chemotherapy-induced nausea and vomiting (CINV), these adverse effects remain among the most uncomfortable conditions for patients and one of the major challenges in cancer therapy.

Cancer patients report nausea as the most uncomfortable adverse effect of chemotherapy. Recently, an antiemetic, mainly serotonin (5-HT3) receptor antagonist, has been used as the go-to treatment for chemotherapy-induced nausea. Despite the extensive usage of antiemetics, chemotherapy-induced nausea persists to be notified by up to 70 % of grown-up cases obtaining moderately emetogenic chemotherapy agents and highly emetogenic chemotherapy agents, and 58 % of school-age children acquiring highly emetogenic chemotherapy.

Nevertheless, the investigation has revealed that antiemetics are clinically efficacious against emesis but not against nausea. Antiemetics confirmed to be successful were presented prophylactically before chemotherapy to control the beginning of nausea or vomiting. Treatment for nausea administered following the insult of chemotherapy are not effective. Again, clinical investigations have indicated that controlling chemotherapy-induced nausea and vomiting in the acute duration is associated with managing delayed nausea and vomiting.

What Is the Pathophysiology of Chemotherapy Induced Nausea and Vomiting?

• Nausea is the personal incident of undesirable, wavelike feeling in the throat, back, and epigastrium that may culminate in vomiting. Vomiting, also known as emesis, is the forceful expulsion of content from the stomach, duodenum, or jejunum via the oral cavity. Retching includes the gastric movement and esophageal motions of vomiting without removal of vomitus, also called dry heaves.

• Advancement has been created in comprehending the neurophysiological mechanisms that prevent nausea and vomiting. Both are regulated or controlled by the central nervous system but by different means. Nausea is moderated via the autonomic nervous system.

• Two primary processes have been proposed in the pathophysiology of the emetic reaction. One is via a central pathway comprising the chemoreceptor trigger zone, placed outside the blood-brain barrier in the medulla oblongata. The further one is via a peripheral pathway, including the vagal afferent nerves in the gastrointestinal tract. Different neurotransmitter receptors, involving dopamine, 5-hydroxytryptamine type 3, neurokinin-1, and cholecystokinin, are triggered by chemotherapy, generating an emetic reaction. The numerous pathways are supposed to be accountable for the diverse kinds of chemotherapy-induced nausea and vomiting. Acute emesis is controlled by the stimulation of the peripheral pathway, while delayed emesis occurs from the inspiration of the central pathway.

What Are the Risk Factors of Chemotherapy Induced Nausea and Vomiting?

Patients obtaining chemotherapy are at increased risk of nausea and vomiting, and the commencement, severity, triggering factors, and period differ. Characteristics associated with the tumor, therapy, and patient all induce nausea and vomiting, involving the tumor area, chemotherapy agents utilized, and radiation exposure.

Patient-corresponding characteristics may possess the following factors:

• Occurrence and severity of nausea and vomiting during previous periods of chemotherapy. Patients with inadequate control of nausea and vomiting at the time of past chemotherapy cycles are likely to experience nausea and vomiting in the following rounds.

• Record of chronic alcohol usage. Cases with a history of increased alcohol intake experienced negligible cisplatin-induced nausea and vomiting.

• Nausea and vomiting are likely to happen in cases younger than 50 and hence it can be age defined.

• Females are at a higher risk of developing nausea, and vomiting than males due to intolearance susceptibility.

• History of morning sickness or emesis at the time of pregnancy.

Other causal elements may involve the following:

• Fluid and electrolyte inequalities, like hypercalcemia, volume deficit, or water intoxication.

• Tumor invasion into the gastrointestinal tract, the liver, or the central nervous system, particularly the posterior fossa.

• Constipation.

• Specific medications like opioids.

• Infection.

• Uremia.

Doctors must be conscious of all possible reasons and characteristics of nausea and vomiting, particularly in cancer patients who may obtain multiple therapies and medicines.

What Is the Treatment of Chemotherapy Induced Nausea and Vomiting?

Pharmacologic Therapy:

• 5-HT3 Antagonists - Serotonin is the primary neurotransmitter in acute chemotherapy-induced nausea and vomiting. The 5-HT3 receptor antagonists obstruct serotonin receptors in the chemoreceptor trigger area and the gastrointestinal tract.

• NK-1 Antagonists - Substance P is another neurotransmitter that mediates chemotherapy-induced nausea and vomiting. The NK-1 receptor antagonists obstruct substance P from binding to its neurokinin receptors and are pivotal in preventing delayed chemotherapy-induced nausea and vomiting.

Other Agents:

• Olanzapine - Olanzapine is an FDA-approved antipsychotic drug that obstructs dopamine, serotonin, and histamine receptors.

• Dexamethasone - Dexamethasone is typically utilized in the prevention and therapy of chemotherapy-induced nausea and vomiting. It functions synergistically, improving the efficacy of other chemotherapy-induced sickness and vomiting agents, although the exact mechanism stays inspired.

• Dopamine Antagonists - Dopamine antagonists like Metoclopramide, Promethazine, and Prochlorperazine are typically utilized for breakthrough chemotherapy-induced nausea and vomiting. Metoclopramide is used slightly continually due to the improved risk for irreversible extrapyramidal side effects involving akathisia, dystonia, tardive dyskinesia, and drug-induced parkinsonism.

• Cannabinoids - The FDA-approved synthetic cannabinoids were used in chemotherapy-induced nausea and vomiting in the 1980s, especially in cases with refractory chemotherapy-induced nausea and vomiting other than conventional antiemetics.

• Nonpharmacologic Therapy - There are numerous nonpharmacologic choices for chemotherapy-induced nausea and vomiting. While pharmacologic treatment remains the mainstay for preventing and treating chemotherapy-induced nausea and vomiting, non-pharmacologic treatments deliver adjunctive help. Clinical investigations have confirmed positive outcomes with the usage of acupuncture and acupressure. Ginger is clinically effective for chemotherapy-induced nausea and vomiting. However, it has yet to be verified what type of chemotherapy-induced nausea and vomiting is best treated with it. Additional non-pharmacologic alternatives are dietary alterations, including a bland diet, small meals, relaxation methods, hypnosis, guided imagery, and behavioral treatment.

Conclusion:

Antiemetic regimens must be assessed and reviewed for certain patients at every therapy cycle. At each stage of patient review and clinical decision-making, clinicians must include value-dependent studies to define the patient’s optimal procedure for therapy. With such a process, we expect to progress in the prophylactic treatment of this disturbing and challenging adverse effect of chemotherapy, thus supporting and enhancing the treatment experience and quality of life.