Chemotherapy-induced Nausea & Vomiting

Overview

What is CINV?

Chemotherapy-induced nausea and vomiting (CINV) is one of the most severe and upsetting side effects of cancer treatment. Nausea is an uneasy feeling in the stomach with the urge to vomit. Vomiting, also called emesis, is an involuntary reflex that pushes the stomach contents out through the mouth.

Not everyone who takes chemotherapy medicines will have nausea and vomiting. Whether a person gets CINV and how severe it will be depends on the type of medicine, dose and factors individual to the patient.

Causes

Nausea and vomiting from chemotherapy is not yet fully understood. It is thought that these medicines activate receptors in the small intestine which send a signal to the part of the brain that triggers vomiting. Damage to intestinal cells from chemotherapy may also make the body release signals that cause vomiting.

Some chemotherapy drugs are more likely to cause CINV than others. Higher doses and combinations of more than one chemotherapy drug increase the risk of CINV.

Women and younger people are more likely to get CINV than men and older people. Genetic differences can also make a person more likely to get CINV. People who have a history of high alcohol intake are less likely to get CINV.

Symptoms

Doctors divide CINV into three categories:

• Acute emesis (vomiting) happens in the first 24 hours after chemotherapy. It usually starts within one or two hours and reaches its worst point between four and six hours.
• Delayed emesis happens more than 24 hours after chemotherapy.
• Anticipatory emesis happens before chemotherapy. It is a conditioned response in patients who have had severe nausea and vomiting from previous cycles of chemotherapy.

Nausea makes people feel like their stomach contents are churning or “doing flips”. Retching occurs when there is no food in the stomach to vomit and only a small amount of clear liquid comes up.

People with CINV may also have raised heart rate, lightheadedness, sweating, dizziness, a pale or grey appearance, increased salivation, loss of appetite and weakness.

CINV usually goes away after one or two days but in some cases it can last for three to four days.

Complications

People lose a lot of fluids from vomiting. If these fluids are not replaced, the body may not have enough to function properly; this is called dehydration. Signs of dehydration include dark urine, dizziness, fatigue, thirst, headache and dry mouth. A healthcare professional can provide more information on how to avoid dehydration.

Ongoing nausea and vomiting can make it difficult to eat well, leading to nutrient deficiencies and weight loss.

Uncontrolled CINV can tear the oesophagus and reopen surgical wounds.

Severe nausea and vomiting may make people withdraw from cancer treatment which would have helped them get better.

Established Treatments

The goal of treatment is to completely prevent CINV. Doctors use anti-nausea medicines called antiemetics for this.

Medicines for CINV

Antiemetic medicines work by blocking signals in the body that trigger vomiting. People usually take antiemetic medicines before chemotherapy and for a few days afterwards. Sometimes different antiemetics are used together. Examples include:

• Ondansetron
• Granisetron
• Dolasetron
• Palonosetron
• Tropisetron
• Ramosetron
• Azasetron
• Dexamethasone
• Aprepitant
• Fosaprepitant
• Rolapitant
• Metoclopramide
• Prochlorperazine
• Olanzapine

Medical Cannabis and Treatment of Nausea and Vomiting

It is thought that cannabis-based medicines suppress nausea and vomiting by interfering with nervous system signals, specifically at the CB1 (endocannabinoid) and 5-HT1A (serotonin) receptors.

The cannabis plant contains many compounds which are active in the human body. At present, most of the research on cannabis for treatment of CINV focuses on THC (tetrahydrocannabinol) and related synthetic compounds.

Doctors are already using cannabis-based medicines to treat CINV in some parts of the world. Guidelines from the National Comprehensive Cancer Network (NCCN) in America and the American Society for Clinical Oncology (ASCO) say that cannabis compounds can be considered for cases of CINV where conventional antiemetics have failed and as a rescue antiemetic

Dronabinol is a man-made, purified form of THC that is approved in the USA for treating CINV. Nabilone, a man-made compound similar to THC, is also approved in the USA for CINV.

Researchers looked at the efficacy of cannabinoids to treat CINV in a systematic review of 28 studies (Whiting et al., 2015). Cannabinoids investigated were nabilone, dronabinol, nabiximols, levonantradol and THC. Studies included a placebo and/or a conventional antiemetic for comparison. The most common antiemetics included were prochlorperazine, chlorpromazine and domperidone. When taken together, all studies suggested a greater benefit from cannabinoids compared with both conventional antiemetics and placebo, but the benefit was not statistically significant in all studies.

The review also found that the risk of side effects was significantly higher with cannabinoids, including serious adverse events. Side effects included dizziness, dry mouth, nausea, fatigue, somnolence, euphoria, vomiting, disorientation, drowsiness, confusion, loss of balance and hallucination.

Currently published research is limited by small sample size and lack of comparison with newer antiemetics. Long term effects of cannabis usage and interactions with other medicines are not yet fully understood. Further large scale, long term clinical trials are needed. One promising study funded by the New South Wales government is currently in progress in Sydney.

• Efficacy of dronabinol alone and in combination with ondansetron versus ondansetron alone for delayed chemotherapy-induced nausea and vomiting
  This trial compared the efficacy and tolerability of dronabinol with a placebo and ondansetron, a conventional antiemetic medicine, in treatment of CINV. This was a double-blind study which means neither patients nor staff knew which treatment was administered.
  
  64 patients receiving chemotherapy were given ondansetron, dronabinol, a combination of both or a placebo for five days. Results showed reduction in nausea and vomiting was similar for ondansetron and dronabinol. Combination therapy was not more effective than either agent alone. Both treatments were well tolerated.
• Cannabis and cancer chemotherapy: a comparison of oral delta-9-THC and prochlorperazine
  This double-blind study compared efficacy and tolerability of THC with traditional antiemetic prochlorperazine in treatment of CINV.
  
  214 patients receiving chemotherapy were given four doses of either THC or prochlorperazine. Both treatments were found to be equally effective in reducing CINV across a wide range of chemotherapy regimens and tumor types
  
  Patients given THC experienced more drug-related side effects, including reduced ability to concentrate, less social interaction and less activity, however these did not reduce preference for the drug.
• Delta-9-tetrahydrocannabinol as an antiemetic for patients receiving cancer chemotherapy. A comparison with prochlorperazine and a placebo
  This double-blind study also compared THC with prochlorperazine and a placebo in treatment of CINV.
  
  116 patients receiving chemotherapy for gastrointestinal carcinoma were given either THC, prochlorperazine or a placebo.
  
  Results found that although THC and prochlorperazine had similar efficacy in reducing CINV, THC had significantly more frequent and severe side effects in the population of largely elderly adults. The study concluded that “THC therapy resulted in an overall more unpleasant treatment experience than that noted with prochlorperazine or placebo”.

References available at end of page.

The Content is not intended to be a substitute for (a) professional medical advice, diagnosis, or treatment; (b) professional legal advice or guidance on legal or regulatory issues; or (c) information from manufacturers or suppliers in relation to products or product information. Always seek the advice of your physician, qualified health provider, qualified lawyer, or authorised manufacture or supplier in respect of such matters. This Site is provided on the basis that all persons accessing the Site undertake responsibility for assessing the relevance and accuracy of the Content.

Related Advocacy Groups

There are several organizations in Australia which provide information and support to people with cancer and their families. Below are links to their websites:

Chemo at Home

Cancer Council Australia

Cancer Australia

Bowel Cancer Australia

Breast Cancer Network Australia

CanTeen

Leukaemia Foundation

Lung Foundation Australia

Myeloma Foundation Australia

National Breast Cancer Foundation

Ovarian Cancer Australia

Prostate Cancer Foundation Australia

Pancreatic Cancer Alliance

References

Please note: this reference material is informational and does not constitute as advice. Furthermore, the information you are being referred to may not comply with the Australian regulatory environment. GreenChoices recommends any information provided should be discussed with a healthcare professional and does not replace their advice.

1. http://www.uptodate.com
2. https://tgldcdp.tg.org.au
3. https://www.cancer.gov
4. https://www.theroc.us/researchlibrary/Regulation%20of%20nausea%20and%20vomiting%20by%20cannabinoids.pdf
5. https://www.ncbi.nlm.nih.gov/pubmed/21827451
6. https://www.medicinalcannabis.nsw.gov.au/clinical-trials/chemotherapy-trial
7. https://jamanetwork.com/journals/jama/fullarticle/2338251?alert=1
8. https://www.ncbi.nlm.nih.gov/pubmed/17355735
9. https://www.ncbi.nlm.nih.gov/pubmed/6284334
10. https://www.ncbi.nlm.nih.gov/pubmed/517882