Chemotherapy Nausea and Vomiting Relief
One of the side effects of chemotherapy that has had major impact on quality of life has been nausea and vomiting. In recent years, with a better understanding of the pathways involved in the chemotherapy induced emesis, new antiemetics have been developed that are very effective. Chemotherapeutic agents activate receptors in the brain and in the intestine that trigger nausea and vomiting. The peripheral pathway is activated during the first 24 hours of giving chemo and causes active emesis. The central pathway located in the brain induces emesis 25-120 hours post chemo and is considerably delayed. In the 70's the dopamine receptors were the target for antiemetics and were not very effective.
With the discovery of the 5-HT3 receptors in the intestine a new class of drugs was introduced in the 90's. The 5-HT3 receptor antagonists ondansetron (Zofran) was the first 5-HT3 receptor inhibitor FDA approved which is given orally every eight hours and was the first drug to have an impact on high ematogenic drugs. Granisetron (Kytril) was approved in 1997 orally and is given every 12 hours. This drug was approved for moderately and highly ematogenic chemotherapy.
In 2003, a second generation 5-HT3 receptor antagonist called palonosetron (Aloxi) was FDA approved. Palonosetron has a prolonged half-life and inhibits 5HT3-NK1 receptor making this drug more effective in preventing acute and delayed vomiting.
The NK1 receptor was another target for antiemetic development and in 2003 aprepitant (Emend) for three days was approved. The NK1 receptor inhibitor combined with 5HT3 receptor inhibitor and decadron showed to be very effective in highly ematogenic chemotherapy.
In 2008, fosaprepitant (Emend IV) the intravenous form of aprepitant was FDA approved which required only one intravenous dose for high ematogenic chemotherapy.
In the last couple of years, nelupitant and rolapitant were two new NK1 receptor inhibitors with a long half-life very efficient for delayed nausea.
The efficiency in preventing nausea and vomiting with 5HT3 receptors and NK1 receptors when combined is 85%.
NCCN/ASCO/ ESMO all have issued guidelines based on ematogenic risk level, which is low, moderate or high.
Adherence to these societies' guidelines has had a major impact on controlling chemotherapy induced emesis.