CURRENT THERAPY FOR CHEMOTHERAPY INDUCED NAUSEA AND VOMITTING

 

Chemotherapy induced nausea and vomiting (CINV) can affect very significantly, the quality of life in cancer patients. Over the last two decades major progress has been made in understanding the pathophysiology of CINV resulting in the development of new drug classes like the 5-HT3 antagonists (5-hydroxytriptamine – 3 receptor antagonists), and the NK1 antagonists.

 

The 5-HT3 receptors are present in the brain and in the gastrointestinal tract, which play a major role in acute CINV ( < 24 hours post therapy). The first generation 5-HT3 antagonists developed are ondansetron (Zofran), granisetron (Kytril) and dolasetron (Anzemet). A second generation 5-HT3 antagonist is palonsetron (Aloxi). These antagonists are excellent in controlling acute CINV as single agents for moderately emetogenic chemotherapy. Granisetron comes in a transdermal patch as well which is very convenient for patients, since it delivers 5 days of antiemetic therapy.

 

The NK1 receptor antagonists are located in the brain stem and play a major role in delayed CINV (24 – 120 hours post therapy). The NK1 receptor antagonists are aprepitant (Emend) oral form or fosaprepitant intravenous preparation.

 

For highly emetogenic chemotherapy (example cisplatin) multiple antiemetic classes are combined to control CINV, the most common combination being a 5-HT3 antagonist combined with an NK1 antagonist and a corticosteroid. It is not clear the exact mechanism by which corticosteroids decrease CINV possibly by decreasing some of the neurotransmitters secreted during the process. It is clear by randomized trials that when they are added to 5-HT3 inhibitors and NK1 inhibitors they improve the efficacy of antinausea treatment by 25 to 30%. In addition to the level of emetogenicity of the chemotherapy used behavior characteristics of specific patients like anxiety or previous vomiting with chemotherapy need to be taken into consideration in which case antianxiety agents like lorazepam (ativan) can be added. Currently, for the vast majority of patients, CINV can be controlled.