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Controlling and assessing nausea
Dr. Richard Gralla
Summary of the presentation given at the TAO Congress on 8/9 December 2016
At the TAO Congress 2016, themed “Tolerability of Immunotherapies”, Dr. Gralla presented the implications for understanding the problem of nausea, a review of several clinical trials in this field and the approach to patients.
Nausea and vomiting are problems in all aspects of cancer care: they are frequent issues in the postoperative period, during chemotherapy and radiotherapy as well as in end-of-life care. Nausea has a very negative effect on quality of life, but is less easy to control than vomiting; a survey of side effects and symptoms in cancer patients between 1983 and 1993 showed that the prevention and treatment of vomiting was improved during that time, whereas hardly any progress was made with regard to nausea. While there is a strong correlation between nausea and vomiting, antiemetic studies nearly always report nausea as exceeding vomiting, in incidence as well as in duration. Furthermore, antiemetic agents always achieve better control of vomiting than of nausea, as shown, for example, by a randomized, double-blind, phase 3 trial comparing olanzapine with placebo, in combination with dexamethasone, aprepitant or fosaprepitant, and a 5-hydroxytryptamine type 3-receptor antagonist (Navari et al.; The New England Journal of Medicine 2016; 375(2): 134–42).
In order to improve the control of nausea, it is important to understand the physiology and neuropharmacology. Vomiting and nausea are related, but nausea is the bigger problem as it is more difficult to control than emesis: a reason for this may be that nausea involves more neurotransmitters. This means that more pathways will have to be targeted in order to achieve an improvement of nausea. Dr. Gralla also discussed another hypothesis which might explain why nausea is more difficult to control: the anti-vomiting effects of antiemetics may work by reducing nausea, so that the nausea stimulus does not reach a vomiting threshold. It has been shown that the vomiting threshold varies: for example, dogs have a lower vomiting threshold than human beings and women are more susceptible to vomiting and nausea than are men. However, the factors that lead to these differences are still unknown. Variations are also seen among individuals. As the perceptible nausea threshold is lower than the vomiting threshold, an individual may perceive nausea without having to vomit. Thus, an antiemetic may prevent nausea and vomiting in one patient, but only vomiting in another patient whose nausea threshold is lower.
Based on these hypotheses, further research is necessary in order to tackle the problem of nausea. As available antiemetic agents decrease nausea as well as vomiting, it should be investigated if agents that affect additional neurotransmitter pathways may help to achieve better control of nausea. Furthermore, future antiemetic trials should use the control of nausea as the primary endpoint instead of primarily focusing on vomiting. Future research will also have to increase the understanding of the physiology involved with nausea and vomiting.
Dr. Richard Gralla, A. Einstein School of Medicine, New York, USA