Treatment of Chemotherapy-induced Nausea in Cancer Patients


problems as they typically do not develop until after the patient has left the treatment location, are often under-reported and are not well controlled by currently available antiemetics.11,24


All in all, there is still room for improvement of control of nausea associated with chemotherapy for cancer. Furthermore, current antiemetics have been associated with significant adverse effects, such as sedation, extrapyramidal side effects and hypotension (associated with dopamine antagonists), as well as headache, diarrhoea or


constipation (associated with serotonin [5-HT3] receptor antagonists). A desirable attribute in any substitute or additional6,7,9,10


antiemetic


medication would be the absence of clinically significant adverse effects. Thus far, two non-invasive and non-toxic interventions have demonstrated promising control of chemotherapy-induced nausea when used in combination with routine antiemetics.


Antiemetics


The most commonly used treatment for chemotherapy-induced nausea and vomiting from moderately and highly emetogenic regimens


is a combination of serotonin (5-HT3) receptor antagonists, a steroid (dexamethasone), and a neurokinin-1 (NK1) receptor antagonist (aprepitant).11,13


The most commonly used anitemetics are the serotonin


(5-HT3) receptor antagonists, including ondansetron (Zofran®), granisetron (Kytril®) and dolasetron mesylate (Anzemet®) and


palosetron. An ondansetron, dexamethasone and aprepitant regimen was able to protect 66–78% of patients from emesis and 50% from nausea during the first cycle of cisplatin-based chemotherapy.11


Serotonin (5-HT3) antiemetics do not significantly reduce delayed nausea and emesis. By contrast, dexamethasone and aprepitant are recommended against delayed nausea and emesis.11,13


Studies have


shown that dexamethasone is the most potent antiemetic for prevention of delayed nausea and vomiting. Furthermore, aprepitant


increases the efficacy of serotonin (5-HT3) antiemetics plus dexamethasone regimens to reduce both acute and delayed chemotherapy-induced nausea and vomiting during highly emetogenic regimens, such as cisplatin.8,11,25


Other neurotransmitter receptors in the gut that are targets of antiemetic medications include dopamine, canniboid, histamine and cholinergic receptors. Dopamine receptor antagonist antiemetics, such as metoclopramide and metopimazine, are primarily used as rescue antiemetics.8,11


Food and Drug Administration (FDA) ‘generally regarded as safe’ (GRAS) list for up to 4g daily. Recently, ginger has been studied scientifically for its effect on nausea and vomiting associated with motion sickness, surgery and pregnancy.21,27–34


Despite the fact that many patients use ginger for prevention or treatment of nausea and vomiting caused by chemotherapy for cancer, only seven studies were found that assessed the efficacy of ginger for chemotherapy-induced nausea and vomiting.14


All studies were in adults


with cancer and five of the seven studies enrolled fewer than 60 subjects. In one of the larger studies, Zick et al. found no difference between placebo and two doses of ginger (1 and 2g) in the prevalence or severity of delayed or acute chemotherapy-induced nausea and vomiting in 162 adults reporting chemotherapy-induced nausea and vomiting with a previous identical chemotherapy cycle (of any emetogenicity).35


Lack of effect could be partly attributed to starting ginger following the start of chemotherapy and an underpowered sample for the secondary aim testing acute effects. Four other small studies found significant reductions in nausea with ginger. In 41 patients being treated for leukaemia with cytosine arabinoside, subjects who received ginger (0.5g) along with Compazine® (prochlorperazine) prior to chemotherapy had significantly less severe nausea on the day of chemotherapy and on the following day than those taking the placebo capsules.36


Another study compared ginger (1.5g) with


psoralen in patients receiving methoxsalen (8-MOP) for extra-corporeal chemotherapy and found that the total nausea score was reduced by approximately one-third in those receiving ginger.37


Sontakke et al.


compared the effects of ginger (4g/day) with metoclopromide and ondansetron in controlling chemotherapy-induced nausea and vomiting in response to low-dose cyclophosphamide.38


Ginger was equally


effective as metoclopromide in achieving complete control, but both were less effective than ondansetron. In the only study demonstrating effectiveness of ginger to reduce delayed chemotherapy-induced nausea, Levine et al. also found less gastric dysrhythmia in subjects taking a high protein drink with 2g of ginger per day.39


At the American Society of Clinical Oncology (ASCO) Annual Meeting 2009, our research group presented the largest study to date investigating the efficacy of ginger in reducing chemortherapy-induced nausea.10


Cannibinoid receptor agonists have shown


antiemetic effectiveness, but their use is restricted due to association with severe adverse events. Despite effectiveness against motion sickeness, antihistamines and anticholinergics have no effect on chemotherapy-related nausea and vomiting.8,11


Ginger Supplementation


Ginger, an ancient tuber mentioned in both the Bible and the Koran, is most known for its role as a flavouring agent for food in Asian and Indian recipes.26


Since the 16th century, the dried aromatic rhizome


(underground stem) of ginger (Zingiber officinale Roscoe), has also been used by practitioners of both Indian (Ayurvedic) and traditional Chinese medicine to treat gastrointestinal upsets such as nausea and excessive flatulence. North American folklore also recognises the ability of ginger to relieve gastrointestinal upsets including nausea. Ginger is also believed to be the only plant that can prevent symptoms of motion sickness and it has been approved for that use by Germany’s Commission E, the agency responsible for regulating the use of herbal products in that country.26


Ginger is on the the US EUROPEAN ONCOLOGY


We demonstrated that three daily doses of ginger (0.5, 1.0 and 1.5g) reduced acute chemotherapy-induced nausea, compared with placebo, in 644 adults receiving chemotherapy for primarily breast, lung and alimentary cancer (90% female, mean age 53 years). In contrast to the other chemotherapy-induced nausea and vomiting studies, we began the administration of ginger three days prior to chemotherapy. We conclude that cancer patients can alleviate chemotherapy-induced nausea by using ginger supplementation (0.5–1.0g daily), which is equivalent to quarter to half a teaspoon of ground ginger, along with the standard 5-HT3 receptor antagonist antiemetics and dexamethasone.10


It


is important to note that the ginger used in this study consisted of capsules containing a purified liquid extract equivalent to 250mg of ginger. The purified liquid extract concentrated the biologically active components of the ginger root, such as gingerols, zingerones and shogaols.27


It is unclear whether ginger in other forms, such as tea, crystallised or raw, would show the same efficacy.


Acupressure


Acupressure has been used for centuries in traditional Chinese medicine to control nausea and vomiting.9,15,40


Acupressure involves acupoint stimulation of the pericardium 6 (P6) located on the anterior 15


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