by Pathophysiology and Classification of Chemotherapy-induced Nausea and Vomiting (CINV)
Nausea and vomiting are common side effects experienced by many cancer patients undergoing chemotherapy treatment. Chemotherapy drugs can directly affect the part of the brain known as the chemoreceptor trigger zone (CTZ), which signals to other parts of the brain and body that nausea and vomiting should occur. The CTZ is sensitive to chemotherapeutic agents as well as to toxic substances in the gastrointestinal tract. When the CTZ is stimulated by these agents, signals are sent to the vomiting center in the medulla, a structure located in the brainstem that controls vomiting. This leads to the activation of the parasympathetic nervous system and causes nausea and vomiting.
Cancer Chemotherapy Associated Nausea And Vomiting Therapeutics can be classified based on when symptoms start in relation to chemotherapy treatment. Acute CINV occurs within 24 hours of chemotherapy administration. Delayed CINV occurs from 24 hours to several days after chemotherapy. Anticipation or expectancy of nausea can also play a role. Breakthrough CINV refers to nausea occurring despite preventive treatment. Each type of CINV involves different pathways in the body and requires tailored treatment approaches. Understanding the pathophysiology and classification of CINV helps guide appropriate prevention and management strategies.
First-generation 5-HT3 Receptor Antagonists for CINV Control
Some of the earliest drugs developed for CINV were the 5-HT3 receptor antagonists, including ondansetron, granisetron, and dolasetron. Serotonin, also known as 5-hydroxytryptamine (5-HT), is one of the key mediators involved in triggering the vomiting reflex in response to chemotherapy. The 5-HT3 receptors are located on neurons in the CTZ and vomiting center. Blocking these receptors was found to be an effective way to prevent both acute and delayed CINV induced by many chemotherapy agents.
The 5-HT3 receptor antagonists revolutionized CINV management when they were introduced in the early 1990s. They helped increase chemotherapy dose intensity and improved patient quality of life compared to previous approaches. However, a significant number of patients still experienced some degree of nausea or vomiting despite 5-HT3 receptor antagonist treatment. This led to the development of newer, multipronged approaches combining different drug classes.
Multidrug Regimens Provide Improved CINV Protection
Clinicians realized more complete prevention of CINV would require targeting additional pathways beyond just 5-HT3 receptors. Combining a 5-HT3 antagonist with other drugs offered synergistic effects. The corticosteroid dexamethasone was added based on its ability to counter inflammation and inhibit prostaglandin and substance P production in the CTZ.
Later, neurokinin-1 (NK1) receptor antagonists such as aprepitant, fosaprepitant, and rolapitant were incorporated into antiemetic regimens. Substance P, which activates NK1 receptors, also contributes to chemotherapy-induced vomiting. Blocking NK1 receptors provided significant protection against both acute and delayed CINV.
Studies demonstrated multidrug combinations significantly outperformed single-drug or two-drug strategies. For example, a triple therapy of 5-HT3 antagonist, dexamethasone, and a NK1 receptor antagonist prior to highly emetogenic chemotherapy reduces both acute and delayed CINV to less than 15% in the majority of patients. This represented a major breakthrough that changed CINV management practice worldwide.
Cancer Chemotherapy Associated Nausea and Vomiting Therapeutics Multidrug regimens are now considered the standard of care for preventing highly and moderately emetogenic chemotherapy-induced nausea and vomiting. Tailoring antiemetic prophylaxis based on individual chemotherapy emetogenicity risk further optimizes CINV control. Ongoing research continues seeking still better strategies to completely prevent this troubling chemotherapy side effect.
Breakthrough CINV Treatments and Non-drug Approaches
Even with optimal prevention using multiple antiemetic agents, some patients may experience breakthrough nausea or vomiting during or between chemotherapy cycles. Rescue medications can help in these situations. The selective NK1 receptor antagonist netupitant, when combined with palonosetron and dexamethasone, was shown highly effective as rescue treatment for CINV not adequately controlled with initial prophylaxis.
Alternative and complementary approaches may also offer adjunctive relief for some patients. Acupuncture, which stimulates points that can suppress nausea in the brain and gastrointestinal tract, showed benefit when added to usual antiemetics in several studies. Relaxation techniques and anti-anxiety medications may help by reducing anticipatory nausea related to chemotherapy expectations. Ensuring adequate hydration and managing gastric emptying can further optimize CINV outcomes. A multidisciplinary approach individualizing prevention and rescue strategies continues advancing this important aspect of supportive cancer care.
Significant advancements have improved management of chemotherapy-induced nausea and vomiting in recent decades. Moving from single agent5-HT3 receptor antagonists to current standard multidrug antiemetic prophylaxis using 5-HT3 antagonists, NK1 receptor antagonists, and dexamethasone has dramatically decreased emesis for most patients receiving highly and moderately emetogenic chemotherapy. Developing new treatments like netupitant can help target refractory or breakthrough nausea as well. Non-pharmacologic adjuncts also offer benefit. Continued research aims to make complete CINV prevention a reality for all through optimized individualized strategies. Reducing this debilitating side effect enhances quality of life and ability to complete chemotherapy for cancer treatment.
*Note:
1. Source: Coherent Market Insights, Public sources, Desk research
2. We have leveraged AI tools to mine information and compile it.
