Anti‐Emetic Therapy in Cancer Chemotherapy: Current Status

Abstract

Nausea and vomiting are ranked as the most severe side effects to chemotherapy by cancer patients. Twenty years ago, treatment of nausea and vomiting from chemotherapy only had moderate effect and often unpleasant side effects. The drugs used included dopamine 2 -receptor antagonists and corticosteroids alone or combined. This review summarizes the development of anti-emetic therapy, but will focus on the importance of two new classes of anti-emetics: the serotonin 3 -and the neurokinin 1 -receptor antagonists. Furthermore, evidence-based guidelines for the treatment of chemotherapy-induced nausea and vomiting will be given. The serotonin 3 -receptor antagonists, the first group of drugs developed specifically as anti-emetics, have significantly improved the prophylaxis of chemotherapy-induced emesis especially in combination with a corticosteroid. The improvement in the prophylaxis of nausea with this combination is however modest. A new group of anti-emetics, the neurokinin 1 -receptor antagonists, has now been developed, and the first drug, aprepitant, was marketed in 2003. Aprepitant increases the effect of a serotonin 3 -receptor antagonist plus a corticosteroid against acute emesis induced by highly or moderately emetogenic chemotherapy and aprepitant is also active in the protection against delayed emesis. The importance of drug-drug interactions with anti-emetics and other drugs, especially cytotoxins, through their competition for cytochrome P450 enzymes, have been studied. At present, there is no evidence that such interactions are of major clinical importance. Evidence-based clinical guidelines are now available and regularly updated, but unfortunately clinical implementation is slow. Recommendations for some types of chemotherapyinduced emesis such as delayed emesis, is based on a low level of evidence. Furthermore, the majority of clinical trials include highly selected groups of patients not permitting definite conclusions for other and more heterogeneous patient groups. Development of new anti-emetics with other mechanisms of action is awaited with interest.

QCM-4, a serotonergic type 3 receptor modulator attenuates depression co-morbid with obesity in mice: An approach based on behavioral and biochemical investigations

“…In obesity chronic stress disturbs feeding pattern and metabolism, linking abdominal obesity and distress (Raikkonen et al, 1996;Bjorntorp, 2001), increases the corticosterone levels that leads to "insulin resistance and altered plasma glucose" (Nonogaki and Iguchi, 1997). 5-HT 3 receptor antagonists are currently used in the management of chemotherapy induced vomiting (Herrstedt and Dombernowsky, 2007). Ion channel coupled 5-HT 3 receptors (Davies et al, 1999) are highly expressed in the area postrema, hippocampus and amygdala (Tecott et al, 1993).…”

Effect of (4a) a novel 5-HT3 receptor antagonist on chronic unpredictable mild stress induced depressive-like behavior in mice: an approach using behavioral tests battery

“…The main therapeutic use of 5-HT 3 receptor antagonist is for chemotherapyinduced emesis [9]. However, other therapeutic uses of 5-HT 3 receptor antagonist have been suggested as in pain, addiction and psychiatric disorders [10].…”

The Role of Yoga in the Complementary Treatment of Cancer

“…However, nausea and vomiting may accompany and often alerts humans to many disease processes, especially those involving the gastro-intestinal tract [82]. Nausea and vomiting is also a common side effect of cancer chemotherapy [83] and can be very distressing [84][85][86][87][88]. It remains one of the most difficult of all side effects to treat in these patients [89,90].…”