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Nausea and vomiting - chemotherapy and radiotherapy induced: prevention and treatment

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Shared care information

Different shared care centres will have different roles in the administration of chemotherapy to paediatric oncology children. In centres where little or no chemotherapy is administered, patients may still present with delayed emesis.

In centres where more chemotherapy is administered, all patients should have antiemetic medication prophylactically prescribed as per the guidelines. Check to see what antiemetics the patient has previously required to determine which level of antiemesis to start at.

Introduction

It is essential during chemotherapy, and for 24 - 48 hours following chemotherapy, to ensure that children receive adequate prophylactic antiemetic therapy. Appropriate management of chemotherapy induced nausea and vomiting decreases anxiety and improves the overall compliance with therapy.

Chemotherapy-induced nausea and vomiting may be:

  • Acute - occurs within a few minutes to several hours after chemotherapy administration and resolves within 24 hours.
  • Delayed - occurs within 24 hours to 5 - 7 days from the administration of chemotherapy. Commonly associated with platinum agents (cisplatin and carboplatin) and anthracyclines. 
  • Anticipatory - conditioned response that leads to nausea and vomiting before chemotherapy administration due to anxiety and previous experiences.
  • Breakthrough - vomiting that occurs despite prophylactic treatments and/or requires "rescue" with antiemetic agents.

Radiation induced nausea and vomiting

This is common in children receiving abdominal radiation but also occurs with radiotherapy for brain tumours and total body irradiation. Radiation-induced vomiting responds to prophylaxis with 5HT3 antagonists such as ondansetron.

Other causes of nausea and vomiting

  • Children with advanced disease with metastases have high rates of nausea and vomiting which can be due to disease or medications being given for symptom control eg morphine.
  • Raised intracranial pressure. Due to tumours or medications
  • Gastrointestinal - gastritis, constipation, abdominal tumours
  • Infections
  • Metabolic abnormalities
  • Medications

Principles of preventing and treating chemotherapy-induced nausea and vomiting

  • Antiemetics should be prescribed and administered regularly during chemotherapy.
  • Antiemetics appropriate for the emetogenic class of the chemotherapy should be administered for each day of chemotherapy and for 2 days after if appropriate (longer for agents that cause delayed emesis).
  • Choice of antiemetics should take into account the emetogenicity of the chemotherapy regimen and the patients history
  • If a patient required an increase in antiemetic therapy for the last cycle of similar chemotherapy they should start a next cycle on this higher regimen.
  • To minimise the risk of nausea and vomiting, the first dose of antiemetics should be given prior to starting chemotherapy
    • Oral - 60 minutes prior to chemotherapy
    • Intravenous - 30 minutes prior to chemotherapy
  • Antiemetics should be charted on the regular chart at the time of admission with a start and end date.
  • Scheduled doses of antiemetics must be given on time regardless of whether the patient is experiencing nausea/vomiting or not.
  • Dexamethasone and 5-HT antagonists have been shown to have synergistic action.

Antiemetic failure

Described as  2 or more episodes of vomiting and/or retching in 24 hours despite being prescribed appropriate antiemetics.

  • Move up the next step of treatment
  • An additional antiemetic should be added, from a different therapeutic class
  • If any medication was previously being given on a "when required" basis, this should be changed to a regular dosing schedule.

Antiemetic prophylaxis for acute chemotherapy induced nausea and vomiting in paediatric cancer patients

The table (1) below has the commonly used chemotherapy agents listed. If the patient is receiving an agent not listed below please also check for a more complete list2.

How to use this table:

  1. Optimal control of nausea and vomiting is defined as4 no vomiting, no retching, no nausea, no use of breakthrough antiemetic agents and no nausea related changes to appetite.
  2. If near optimal control is not achieved using first line therapy then the addition of second line agents for the current and subsequent cycles should occur.
  3. The level of antiemetic therapy required is based on the most emetogenic agent in the combination chemotherapy regimen.
  4. See notes below for when steroids should not be used, drug interactions etc. The uses of steroids should be discussed with a consultant.
  5. If anticipatory nausea and vomiting occurs see management of anticipatory nausea and vomiting.
  6. Patients receiving cisplatin are at high risk for delayed emesis and need scripts for prophylactic antiemetics. Patients receiving high dose cyclophosphamide or ifosfomide, anthracyclines or carboplatin may also develop this and should also have medication available at home.

Table 1 - Prophylaxis and treatment for acute chemotherapy induced nausea and vomiting in paediatric cancer patients

Click on image below to access a pdf of the Table.

Table 1

Doses

Aprepitant3,4,5
 > 12 years  125mg/80mg/80mg daily*
 6 months - 11.99 years5  
 Cooks Children Medical Centre:  
 25 to 40kg  80mg daily on day 1,2 and 3
 15 to 24kg  80mg on day 1, then 40mg daily on day 2 and 3
<15kg 40mg daily on day 1,2 and 3
*multiday use for longer chemotherapy courses (e.g. Ifos/Etop - 5/7) can be considered if institutional standard.
Aprepitant use is HML restricted to patients undergoing highly emetogenic chemotherapy and/or anthracycline-based chemotherapy.
Use in children under the age of 12 is unlicensed at the discretion of the consultant.
Check COG protocol prior to prescribing, as aprepitant use may be prohibited in some protocols.
Dexamethasone4
 High start at 2-6mg/m2/dose q12h max 15mg/day
Resistant CINV: 6mg/m2/dose q6h max 20mg/day
(halve dex dose if using aprepitant)
 Moderate  <0.6m2 2mg/dose q12h>0.6m2 4mg/dose q12h
Dexamethasone should always be charted with a stopping date on the QMR4.
Levomepromazine
 Restlessness and confusion in palliative care Continuous subcutaneous infusion
0.5 - 3mg/kg over 24 hours
 Nausea and vomiting in palliative care Continuous intravenous infusion or subcutaneous infusion
Child 1 month to 12 years: 100 - 400 micrograms/kg over 24 hours
Child 12 - 18 years: 5 - 25 mg over 24 hours
Metoclopramide6
0.15mg/kg/dose q6h
(usual max dose is 10mg but can go to 20mg for resistant nausea and vomiting - given with Scopaderm (hyosceine) to prevent extrapyramidal side effects)
Ondansetron4,7
 0.15mg/kg/dose
Usual max dose 8mg however higher doses at 0.15mg/kg/dose can be considered for children >55kg not controlled on first line therapy
STAT dosing - 0.3mg/kg/dose Maximum single dose 16mg
Maximum adult daily dose 32mg. Maximum frequency Q2-4hr

Patients with delayed emesis and all patient receiving Cisplatin

Delayed emesis occurs within 24 hours to 5 - 7 days from the administration of chemotherapy. Delayed emesis is most common with cisplatin but also seen with high dose cyclophosphamide, doxorubicin, carboplatin and Ifosfomide. It is more likely when these drugs are used in combination.

To decrease the incidence and severity of delayed chemotherapy induced nausea and vomiting (CINV) the first step is pre-emptive management of the acute phase of CINV - see Prophylaxis and Treatment table above.

Oral dexamethasone is very effective but the total dose given over the cycle(s) and steroid side effects need to be considered. If the dexamethasone dose was halved due to interaction with aprepitant this can be increased 48 hours after the last dose of aprepitant.

If delayed nausea and vomiting then occur treatment with ondansetron +/- dexamethasone +/- metoclopramide or cyclizine should be restarted and again given regularly to prevent breakthrough until symptoms subside.

If symptoms persist 5-7 days after chemotherapy further investigation for other possible causes should be undertaken.

Managing anticipatory nausea and vomiting (ANV) in paediatric cancer patients

Antiemetic therapy should be optimised from the first cycle to prevent the development of anticipatory nausea and vomiting - see antiemetic prophylaxis for acute chemotherapy induced nausea and vomiting in paediatric cancer patients

Psychological interventions, where available, should be utilised to help manage ANV.

Lorazepam (0.04-0.08mg/kg/dose max 2mg) may be used the night before day 1 of the chemotherapy cycle and a second dose 12 hours later the morning of chemotherapy if required. Regular use of multiple days of Lorazepam for multiday chemotherapy cycles is discouraged due to the risk of benzodiazepine tolerance.

References

  1. Handbook of supportive care in pediatric oncology. Ed Oussama Alba. SickKids Toronto hospital for sick children. 2009 Pub: Jones and Bartlett.
  2. Dupuis L et al. Guideline for the classification of acute emetogenic potential of antineoplastic medication in pediatric cancer patients. PBC 2011, 57:191-198.
  3. Duggan et al. Aprepitant reduces chemotherapy induced vomiting in children and young adults with brain tumours. Journal of Pediatric Oncology Nursing. 2014 31(5) 277-283
  4. Dupuis et al. guideline for the prevention of acute nausea and vomiting due to antineoplastic medication in pediatric cancer patients. Paediatric Blood and Cancer. 2013; 9999:1-10.
  5. Kang et al. Aprepitant for the prevention of chemotherapy induced nausea and vomiting in children. A randomised double blind phase 3 trial. Journal of Clinical Oncology. 2015 16:385-94.
  6. Medsafe data sheet Metaclopramide 29 April 2013.
  7. Medsafe data sheet Ondansetron 24 September 2014.

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Document Control

  • Date last published: 27 July 2016
  • Document type: Clinical Guideline
  • Services responsible: National Child Cancer Network
  • Owner: Siobhan Cross
  • Review frequency: 2 years