Cancer Chemotherapy Associated Nausea and Vomiting Therapeutics: Breaking Down Progress in Treatment Options

Managing Side Effects of Chemotherapy

One of the most common and distressing side effects experienced by cancer patients undergoing chemotherapy is nausea and vomiting. Chemotherapy drugs work by targeting fast-growing cells like cancer, but they can also affect healthy cells in the gastrointestinal tract that are regularly replaced, causing nausea and vomiting. Until recent decades, nausea and vomiting associated with chemotherapy was a major challenge with few effective treatment options. However, advances in anti-emetic therapies have significantly improved symptom management.

5-HT3 Receptor Antagonists Lead the Way

Cancer Chemotherapy Associated Nausea And Vomiting Therapeutics first major breakthrough was the development of 5-HT3 receptor antagonists in the early 1990s. 5-HT3 receptors are located on the vagus nerve and in the chemoreceptor trigger zone of the brain, areas involved in causing nausea and vomiting. Drugs that block these receptors like ondansetron were found to be highly effective in reducing acute vomiting following chemotherapy. They became the standard first-line treatment for prevention of nausea and vomiting from highly emetogenic chemotherapy. Later innovations added additional 5-HT3 drugs like granisetron and palonosetron with enhanced efficacy profiles.

NK1 Receptor Antagonists Add Robust Prevention

While 5-HT3 receptor antagonists revolutionized control of acute vomiting, they were less effective against delayed and long-term nausea. The discovery of neurokinin-1 (NK1) receptors in the 1990s and development of NK1 receptor antagonists like aprepitant helped address this unmet need. When added to standard 5-HT3 and corticosteroid therapy, NK1 antagonists were shown to significantly reduce risk of both acute and delayed chemotherapy-induced nausea and vomiting even with highly emetogenic regimens. This three-drug combination became the new standard for optimal prevention.

Multiday Dosing Resolves Breakthrough Issues

Despite advances, Cancer Chemotherapy Associated Nausea and Vomiting some patients still experienced occasional breakthrough nausea or vomiting while undergoing repeat chemotherapy cycles over months. This prompted researching different dosing schedules for anti-emetic drugs. Clinical trials found that extending the duration of NK1 receptor antagonist administration over multiple days matched to the chemotherapy regimen dramatically reduced breakthrough rates compared to single-dose therapy. This led to approval of 3-day and even 5-day extended regimens using NK1 antagonists that provided more complete control of nausea for the entire chemotherapy treatment period.

Guidance Tailors Combinations to Chemotherapy Risk

With numerous anti-emetic options available, treatment guidelines from professional societies seek to optimize prevention based on individual chemotherapy regimens and patient risk factors. Highly emetogenic agents require combination therapy with a 5-HT3, NK1, and corticosteroid, while moderately emetogenic regimens may only require two agents. Guidelines also account for repeated chemotherapy administration and past history to minimize all nausea. This risk-adapted, multi-drug approach has allowed over 90% of patients to avoid emesis altogether following chemotherapy.

Additional Areas for Future Improvement

While major advances have been achieved, ongoing research continues toward developing even more effective and personalized anti-emetic treatments. Areas of active investigation include safer, longer-acting NK1 drugs to replace aprepitant, refined guidelines incorporating newer regimens and biomarkers, integrating nonpharmacologic aids, and studying underreported patient populations like pediatric and breast cancer patients. Additional receptor targets beyond 5-HT3 and NK1 are also under exploration that may lead to the next generation standard of care. Overall, investigators remain dedicated to further enlarging the therapeutic window and improving quality of life for the growing number of cancer patients worldwide.

One of the most common and distressing side effects experienced by cancer patients undergoing chemotherapy is nausea and vomiting. Chemotherapy drugs work by targeting fast-growing cells like cancer, but they can also affect healthy cells in the gastrointestinal tract that are regularly replaced, causing nausea and vomiting. Until recent decades, nausea and vomiting associated with chemotherapy was a major challenge with few effective treatment options. However, advances in anti-emetic therapies have significantly improved symptom management.

5-HT3 Receptor Antagonists Lead the Way

Cancer Chemotherapy Associated Nausea And Vomiting Therapeutics first major breakthrough was the development of 5-HT3 receptor antagonists in the early 1990s. 5-HT3 receptors are located on the vagus nerve and in the chemoreceptor trigger zone of the brain, areas involved in causing nausea and vomiting. Drugs that block these receptors like ondansetron were found to be highly effective in reducing acute vomiting following chemotherapy. They became the standard first-line treatment for prevention of nausea and vomiting from highly emetogenic chemotherapy. Later innovations added additional 5-HT3 drugs like granisetron and palonosetron with enhanced efficacy profiles.

NK1 Receptor Antagonists Add Robust Prevention

While 5-HT3 receptor antagonists revolutionized control of acute vomiting, they were less effective against delayed and long-term nausea. The discovery of neurokinin-1 (NK1) receptors in the 1990s and development of NK1 receptor antagonists like aprepitant helped address this unmet need. When added to standard 5-HT3 and corticosteroid therapy, NK1 antagonists were shown to significantly reduce risk of both acute and delayed chemotherapy-induced nausea and vomiting even with highly emetogenic regimens. This three-drug combination became the new standard for optimal prevention.

Multiday Dosing Resolves Breakthrough Issues

Despite advances, Cancer Chemotherapy Associated Nausea and Vomiting some patients still experienced occasional breakthrough nausea or vomiting while undergoing repeat chemotherapy cycles over months. This prompted researching different dosing schedules for anti-emetic drugs. Clinical trials found that extending the duration of NK1 receptor antagonist administration over multiple days matched to the chemotherapy regimen dramatically reduced breakthrough rates compared to single-dose therapy. This led to approval of 3-day and even 5-day extended regimens using NK1 antagonists that provided more complete control of nausea for the entire chemotherapy treatment period.

Guidance Tailors Combinations to Chemotherapy Risk

With numerous anti-emetic options available, treatment guidelines from professional societies seek to optimize prevention based on individual chemotherapy regimens and patient risk factors. Highly emetogenic agents require combination therapy with a 5-HT3, NK1, and corticosteroid, while moderately emetogenic regimens may only require two agents. Guidelines also account for repeated chemotherapy administration and past history to minimize all nausea. This risk-adapted, multi-drug approach has allowed over 90% of patients to avoid emesis altogether following chemotherapy.

Additional Areas for Future Improvement

While major advances have been achieved, ongoing research continues toward developing even more effective and personalized anti-emetic treatments. Areas of active investigation include safer, longer-acting NK1 drugs to replace aprepitant, refined guidelines incorporating newer regimens and biomarkers, integrating nonpharmacologic aids, and studying underreported patient populations like pediatric and breast cancer patients. Additional receptor targets beyond 5-HT3 and NK1 are also under exploration that may lead to the next generation standard of care. Overall, investigators remain dedicated to further enlarging the therapeutic window and improving quality of life for the growing number of cancer patients worldwide.

​Get more insights, On Cancer Chemotherapy Associated Nausea and Vomiting Therapeutics