In 2018 alone, there is estimated to be 138,321 new cases of cancer and 48,586 deaths due to cancer. One of the main treatments used is chemotherapy, with nausea and vomiting tending to be common side effects experienced by patients. Depending on the extent of chemotherapy-induced nausea and vomiting (CINV), it can affect a person’s lifestyle, quality of life, and perception and compliance to further cancer treatments. In extreme scenarios, it can cause metabolic imbalances, nutrient depletion, anorexia, degeneration of patient’s performance and mental status, oesophageal damage, wound ruptures, and complete withdrawal from possibly beneficial anticancer treatment.

CINV can vary based on the onset, severity, and duration, which is influenced by the specific chemotherapy agent or combination of agents used, dosage, route, and schedule of administration. The following factors also increase a patient’s risk of having CINV:

  • Young women (<50 years of age);
  • Prior chemotherapy;
  • History of motion sickness and/or nausea in pregnancy;
  • Poor health status;
  • Experienced CINV with earlier treatments; and
  • No alcohol consumption.

There are several types of nausea and vomiting related to chemotherapy which can be classified as shown in Table 1.

Table 1. Classification of chemotherapy-induced nausea and vomiting

Type of CINV Description
Acute Occurs within the first 24 hours of chemotherapy treatment, peaking within 5 to 6 hours. The dosage of chemotherapy and antiemetic regimen used can influence patients’ experience.
Delayed Occurs more than 24 hours after chemotherapy and may last for 6 to 7 days. Patients commonly experience this after administration of cisplatin, carboplatin, cyclophosphamide and/or doxorubicin.
Anticipatory Occurs before patients’ next chemotherapy administration that is triggered by a negative past experience. Incidence can range from 18% to 57% where nausea tends to be more common than vomiting. Younger patients are more susceptible due to a more aggressive treatment regimen and overall, poorer emesis control than older patients. Stimuli that reminds a patient of the treatment room and its surroundings is sufficient to trigger nausea and vomiting.
Breakthrough CINV that occurs even though patients are receiving prophylactic antiemetic agents, thus requiring the addition of rescue antiemetic medication.

Patients undergoing chemotherapy should be monitored for signs of dehydration such as postural hypotension, tachycardia, low urine output, and headaches. Patients can also present with other symptoms like paleness, diaphoresis/increased sweating, salivation, and in extreme cases, anorexia. Because nausea and vomiting are non-specific symptoms, it is important to distinguish and exclude chemotherapy from other potential triggers such as:

  • Constipation;
  • Bowel obstruction;
  • Gastroparesis;
  • Malignant ascites;
  • Anxiety;
  • Fluid and electrolyte imbalances (e.g. hypercalcaemia and renal failure);
  • Uraemia;
  • Metastases or tumour site involving the gastrointestinal tract, liver, or central nervous system;
  • Raised intracranial pressure;
  • Peptic ulcer disease;
  • Recent or concurrent radiation therapy; and
  • Vestibular dysfunction.

The severity of CINV experienced can be classified into grades as shown in Table 2.

Table 2. Chemotherapy-induced nausea and vomiting grades

Grade Vomiting Nausea
1 1-2 episodes (5 minutes apart) in 24 hours Loss of appetite without a change in eating habits
2 3-5 episodes (5 minutes apart) in 24 hours Oral intake decreases without significant weight loss, dehydration or malnutrition
3 Equal or more than 6 episodes (5 minutes apart) in 24 hours. Feeding, TPN or hospitalisation indicated. Inadequate food or fluid intake.
4 Life-threatening, urgent intervention needed. Feeding, TPN or hospitalisation indicated.
5 Death

 

In non-urgent situations where immediate medical intervention is not required, healthcare professionals can provide support and patient education. Lifestyle recommendations which can be discussed are:

  • Frequent small meals (5 to 6 times daily) and chew food well. Do not lie down immediately after eating;
  • Eat food cold or warm (not hot);
  • Increase fluid intake to 8 – 10 cups daily (2 to 2.5 litres a day) via soups, popsicles, and small sips (caution if the patient is on a fluid restriction);
  • Have assistance in preparing meals;
  • Avoid alcohol or tobacco;
  • Avoid foods or fluids that are spicy, fatty or have a strong taste or smell;
  • Limit caffeine intake; and
  • Peppermint tea and food with ginger may be of benefit.

Patients with dyspepsia may benefit from an antacid like a proton-pump inhibitor or H2-receptor antagonist.

A chemotherapy agent can be differentiated based on its likelihood to cause emesis as shown in Table 3.

Table 3. Emesis risk of chemotherapy agents

IV Drugs Oral Drugs
 Minimal emetogenic risk (<10%)  Minimal-to-low emetogenic risk (<30%)
  • Alemtuzumab, asparaginase (colaspase)
  • Bevacizumab, bleomycin, bortezomib
  • Cetuximab, cladribine
  • Fludarabine
  • Ipilimumab
  • Methotrexate (<50mg/m2)
  • Nivolumab
  • Obinutuzumab, ofatumumab
  • Panitumumab, pembrolizumab, pertuzumab, pralatrexate
  • Rituximab
  • Temsirolimus, trastuzumab
  • Vinblastine, vincristine, vinorelbine
  • Afatinib, alectinib, axitinib
  • Busulfan (<4mg daily)
  • Capecitabine, chlorambucil, cobimetinib, cyclophosphamide (<100mg/m2 daily)
  • Dabrafenib, dasatinib
  • Erlotinib, everolimus
  • Fludarabine
  • Gefitinib
  • Hydroxycarbamide (hydroxyurea)
  • Ibrutinib, idelalisib, imatinib
  • Lapatinib, lenalidomide
  • Melphalan, mercaptopurine, methotrexate
  • Nilotinib
  • Pazopanib, pomalidomide, ponatinib
  • Regorafenib, ruxolitinib
  • Sorafenib, sunitinib
  • Temozolomide (<75mg/m2 daily), thalidomide, tioguanine, trametinib, tretinoin
  • Vemurafenib, venetoclax, vismodegib, vorinostat
Low emetogenic risk (10–30%)
  • Blinatumomab, brentuximab vedotin
  • Cabazitaxel, carfilzomib, cytarabine (<1 g/m2)
  • Docetaxel, doxorubicin (liposomal)
  • Eribulin, etoposide
  • Fluorouracil
  • Gemcitabine
  • Methotrexate (50–250mg/m2), mitomycin, mitozantrone
  • Paclitaxel, pemetrexed
  • Romidepsin
  • Topotecan, trastuzumab emtansine
  • Vinflunine

 

Moderate emetogenic risk (30–90%)  Moderate-to-high emetogenic risk (>30%)
  • Arsenic trioxide, azacitidine
  • Bendamustine, busulfan
  • Carboplatin, carmustine (<250mg/m2), clofarabine, cyclophosphamide (<1500mg/m2 without anthracycline), cytarabine (>1 g/m2)
  • Dactinomycin, daunorubicin, doxorubicin
  • Epirubicin
  • Fotemustine
  • Idarubicin, ifosfamide, irinotecan
  • Melphalan, methotrexate (>250mg/m2)
  • Oxaliplatin
  • Raltitrexed
  • Busulfan (>4mg daily)
  • Ceritinib, crizotinib, cyclophosphamide (>100mg/m2 daily)
  • Etoposide
  • Idarubicin
  • Lenvatinib, lomustine
  • Olaparib
  • Procarbazine
  • Temozolomide (>75mg/m2 daily)
  • Vinorelbine
High emetogenic risk (>90%)
  • Carmustine (>250mg/m2), cisplatin, cyclophosphamide (>1500mg/m2 and <1500mg/m2 with anthracycline)
  • Dacarbazine

 

Generally, the ultimate goal is to have zero occurrences of nausea or vomiting. A regimen is chosen based on the emetic risk of chemotherapy, patient’s experience with antiemetics, and patient-specific risk factors. Over 90% of patients having highly emetogenic chemotherapy will experience episodes of vomiting. However, this figure is reduced to approximately 30% when patients receive prophylactic antiemetic agents. Although vomiting may often be prevented or decreased using prophylactic regimens, nausea is more challenging to control. Antiemetic therapy should be started before chemotherapy for maximum protection against CINV, and ideally, should be continued for the duration of the emetic activity of the chemotherapy agent. A patient needs to be covered for at least three days after the last dose of highly emetogenic chemotherapy has been administered, whilst moderate risk treatments often require two days of coverage.

It is recommended that all oral anti-nausea medication is administered an hour before treatment whereas intravenous doses are to be given 30 minutes prior to chemotherapy. Table 4 provides some general anti-nausea recommendations.

Table 4. General antiemetic regimens

Emesis Risk Acute CINV Delayed CINV
>90% (high risk) Neurokinin (NK1) receptor antagonist + 5HT3 receptor antagonist AND dexamethasone Dexamethasone
30% to 90% (moderate risk) Palonosetron 0.25mg IV PLUS dexamethasone 8mg oral or IV Dexamethasone 8mg oral or IV once daily
10% to 30% (low risk) Dexamethasone 4-8mg oral or IV OR metoclopramide 10mg when required OR prochlorperazine 10mg oral or 12.5mg IV when required Antiemetics may not be required
<10% (minimal risk) Antiemetic regimen may not be required, but patients who experience CINV can follow the regimen for low risk
Breakthrough Patients can be supplied with an agent from a different class, and in some severe cases, patients may require several antiemetic agents with different mechanisms of action.

Some common drugs that can be used:

  • Ondansetron: 8mg orally or intravenously twice daily (maximum 32mg per 24 hours)
  • Metoclopramide: 10mg orally or IV three times a day (up to 30mg per 24 hours for 5 days)
  • Prochlorperazine: 10mg orally or 12.5mg IV every 6 hours
  • Lorazepam: 0.5mg to 2mg orally/sublingually every 6 hours when required
Anticipatory Avoid strong smells that may precipitate nausea; behavioural therapy may be of use. If required, lorazepam 0.5mg – 2mg beginning the night prior to treatment and repeat on the day of treatment 1-2 hours before chemotherapy.

 

In conclusion, it is easier to prevent nausea and vomiting than it is to treat it. Prevention is important, and optimal antiemetic therapy should be used during each cycle where round the clock anti-nausea treatment is preferred rather than on a when required basis. Patients also need to be adequately hydrated and be observed for signs of dehydration.

References:

  1. Cancer Australia. All Cancers in Australia. Surry Hills: Australian Government; 2017.
  2. Cancer Institute NSW. Prevention of Chemotherapy Induced Nausea and Vomiting. Eveleigh: eviQ Cancer Treatments Online; 2017.
  3. Ettinger DS, Berger MJ, Aston J, Barbour S, Bergsbaken J, Bierman PJ, et al. NCCN Clinical Practice Guidelines in Oncology: Antiemesis [v.2.2017]. Fort Washington: National Comprehensive Cancer Network; 2017.
  4. Huebert K, Van der Meer L. Symptom Management Guidelines: Cancer Related Nausea and Vomiting. Vancouver: BC Cancer Agency; 2014.
  5. Rossi S, editor. Immunomodulators and antineoplastics. In: Australian Medicines Handbook 2018 [online]. Adelaide: Australian Medicines Handbook Pty Ltd; 2018.

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