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Guidelines for Prevention and Treatment of Chemotherapy-Induced

Nausea and Vomiting in Adults


Protocol Code

SCNAUSEA

Tumour group

SUPPORTIVE CARE

Physician Contact

Dr. Paul Hoskins

ELIGIBILITY
Adults receiving chemotherapy.
Drug acquisition: Antiemetics are considered supportive treatment. These agents are not
BCCA benefit drugs and are not covered by any BCCA program. Patients being treated with
these agents should have prescriptions filled at a community pharmacy and must arrange
their own payment for the drugs.
EXCLUSION CRITERIA
Pediatric patients.
Radiation-induced nausea and vomiting.
APPROACH TO TREATMENT
The goal is NO nausea or vomiting.1-3
It is far easier to prevent nausea and vomiting than to treat it.1,2
Anticipatory nausea and vomiting is a conditioned response, and can only happen after a
negative past experience.1,2
Ensure optimal antiemetic therapy for every cycle of chemotherapy.
Use of guidelines: This is a general reference and is not intended to replace the clinical
judgment of individual practitioners caring for individual patients.

BC Cancer Agency - SCNAUSEA Protocol

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Warning: The information contained in these documents are a statement of consensus of BC Cancer Agency professionals regarding their views of currently accepted approaches to treatment. Any clinician
seeking to apply or consult these documents is expected to use independent medical judgement in the context of individual clinical circumstances to determine any patient's care or treatment. Use of these
documents is at your own risk and is subject to BC Cancer Agency's terms of use available at www.bccancer.bc.ca/legal.htm

PROPHYLACTIC ANTIEMETIC REGIMENS


For multiple days of chemotherapy, repeat antiemetics before each treatment.
EMETOGENICITY

PRE-CHEMOTHERAPY

POST-CHEMOTHERAPY

High

ONE 5-HT3 ANTAGONIST:


ondansetron 8 mg po
granisetron 1 mg po

aprepitant 80 mg po daily x 2 days2,8,9

PLUS:**
dexamethasone 8-12 mg po1-3
PLUS:
aprepitant* 125 mg po7-9

High-moderate
Low-moderate

ONE 5-HT3 ANTAGONIST:


ondansetron 8 mg po
granisetron 1 mg po

PLUS:**
dexamethasone 4 mg po evening of
chemo,3 then 4 mg po BID x 2-5 days2,3
AND ONE ANTIEMETIC AS-NEEDED:
prochlorperazine 10 mg po every 4-6
hours PRN x 3-4 days1-3 OR
metoclopramide 10-40 mg po every 4-6
hours PRN x 3-4 days1-4
dexamethasone 4 mg po evening of
chemo,3 then 4 mg po BID x 2-3 days2,3

AND ONE ANTIEMETIC AS-NEEDED:


prochlorperazine 10 mg po every 4-6
hours PRN x 3-4 days1-3 OR
metoclopramide 10-40 mg po every 4-6
hours PRN x 3-4 days1-4
Low
PREFERRED:
dexamethasone 4 mg BID for up to 2-3
dexamethasone 4-12 mg po1,2
days1-3 OR
prochlorperazine 10 mg po every 4-6
ALTERNATE:
hours PRN x 3-4 days1-3 OR
prochlorperazine 10 mg po OR metoclopramide 10-40 mg po every 4-6
metoclopramide 20-40 mg po2
hours PRN x 3-4 days1-4
Rare
Prophylactic treatment not
prochlorperazine 10 mg po every 4-6
normally required.
hours PRN x 3-4 days1-3 OR
metoclopramide 10-40 mg po every 4-6
hours PRN x 3-4 days1-4
For prophylaxis after prior treatment failures, refer to Figure 1.
PLUS:
dexamethasone 8-20 mg po1-3

*For inpatients unable to swallow:

consider replacing pre-chemotherapy aprepitant with fosaprepitant IV 150 mg

post-chemotherapy fosaprepitant NOT needed,2,9,10 dose of 5-HT3 antagonist and dexamethasone


remain the same (fosaprepitant 150 mg confers comparable serum level to aprepitant 125 mg11 which
seems sufficient to cover days 2 and 312)
**If patients do not receive aprepitant /fosaprepitant, may increase dexamethasone to 20 mg day 1 and
16 mg BID days 2 to 41

TREATMENT NOTES
Oral and IV formulations of 5-HT3 antagonists are equally effective. If IV administration is
clinically indicated, use same doses.3
Single doses of 5-HT3 antagonists are as effective as multiple doses.3,5
Currently available 5-HT3 antagonists (ondansetron, granisetron) are equally effective.
Choose based on availability and cost.1-3,5
1. Ondansetron may increase the risk of arrhythmia and Torsade de Pointes in patients:
with congenital long QT syndrome
with pre-existing hypokalemia or hypomagnesemia, or
BC Cancer Agency - SCNAUSEA Protocol

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Warning: The information contained in these documents are a statement of consensus of BC Cancer Agency professionals regarding their views of currently accepted approaches to treatment. Any clinician
seeking to apply or consult these documents is expected to use independent medical judgement in the context of individual clinical circumstances to determine any patient's care or treatment. Use of these
documents is at your own risk and is subject to BC Cancer Agency's terms of use available at www.bccancer.bc.ca/legal.htm

using medications that prolong QT interval.


ECG monitoring is recommended in patients with electrolyte abnormalities, congestive
heart failure, bradyarrhythmias, or taking concomitant medications that prolong the QT
interval.13 Results from an ongoing FDA safety review are expected in early 2012.14
2. Dolasetron is not recommended due to increased risk of QT prolongation and Torsades
de Pointes.15

Except for highly emetogenic chemotherapy, a corticosteroid alone is the cornerstone of


therapy for prevention of delayed nausea and vomiting. There is no role for the routine use
of 5-HT3 antagonists more than 24 hours after chemotherapy.1-3,6

DETERMINING EMETOGENICITY OF CHEMOTHERAPY


Emetogenicity: percentage of patients who will experience emesis if not treated.
o high greater than 90%
o high-moderate = 60% to 90%
o low-moderate = 30% to less than 60%
o low = 10% to less than 30%
o rare less than 10%
Single agent chemotherapy: consult Cancer Drug Manual.
Combination chemotherapy:
o Consult chemotherapy protocol.
o If emetogenicity is not specified, consult Cancer Drug Manual.
o Treat for the most emetogenic agent1 OR use Hesketh Algorithm.
HESKETH ALGORITHM7
Identify the most highly emetogenic agent in the combination, then add the contribution of
other agents using the following rules:
o high, high-moderate, low-moderate: increase the emetogenicity of the combination
by one level per agent.
o low: increase the emetogenicity of the combination by one level, regardless of how
many such agents are added.
o rare: do not contribute.
TREATMENT FAILURES
If a patient experiences nausea or vomiting despite optimal prophylactic therapy, complete
steps 1, 2, and 3 as follows:
1. Rule out or treat other causes of nausea and vomiting:
o intestinal obstruction,1,2 gastroparesis,2 gastritis1
o medications (pain meds, bronchodilators)1,2
o brain metastases1,2
o vestibular dysfunction2
o electrolyte imbalance,2 uremia2
o infection1
2. Control this episode of nausea and vomiting.
Approach to treatment2:
o give additional antiemetic agent from a different class
o use rectal or iv route of administration if patient is vomiting
o consider around-the-clock dosing rather than prn
BC Cancer Agency - SCNAUSEA Protocol

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Warning: The information contained in these documents are a statement of consensus of BC Cancer Agency professionals regarding their views of currently accepted approaches to treatment. Any clinician
seeking to apply or consult these documents is expected to use independent medical judgement in the context of individual clinical circumstances to determine any patient's care or treatment. Use of these
documents is at your own risk and is subject to BC Cancer Agency's terms of use available at www.bccancer.bc.ca/legal.htm

o monitor hydration and electrolytes


o may need to use multiple agents in alternating schedules
Consider admission to hospital.
Possible antiemetic regimens include:
o dexamethasone 12 mg po/iv daily, if not previously given2
o prochlorperazine 25 mg pr q12h or 10 mg po/iv q4-6h2
o metoclopramide 20-40 mg po q4-6h or 1-2 mg/kg iv q3-4h diphenhydramine 25-50
mg po/iv q4-6h2
o lorazepam 0.5-2 mg po or sl q4-6h2
o haloperidol 1-2 mg po q4-6h or 1-3 mg iv q4-6h2
o dimenhydrinate 100mg po q12h alternating with prochlorperazine 10 mg po q12h (for
a q6h regimen)3

3. Plan prophylactic regimen for next cycle using Figure 1.

BC Cancer Agency - SCNAUSEA Protocol

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Warning: The information contained in these documents are a statement of consensus of BC Cancer Agency professionals regarding their views of currently accepted approaches to treatment. Any clinician
seeking to apply or consult these documents is expected to use independent medical judgement in the context of individual clinical circumstances to determine any patient's care or treatment. Use of these
documents is at your own risk and is subject to BC Cancer Agency's terms of use available at www.bccancer.bc.ca/legal.htm

Figure 1. SUBSEQUENT ANTIEMETIC REGIMENS AFTER TREATMENT FAILURE


no

Did patient have ANY nausea or vomiting last cycle?

continue current
management

yes
Anxiety or signs of
anticipatory nausea
and vomiting?

yes

continue optimal prophylactic regimen and add one or more of:


lorazepam 0.5-2 mg PO/SL q12h, start the night before chemo2,3
behavioural therapy (e.g., relaxation, hypnosis, music therapy)1-3

no
Vomited within 24 h
of chemo?

acute nausea and vomiting:


Is patient on highest pre-chemo
antiemetic regimen?

yes

no

yes

no

Vomited > 24 h after


chemo?

increase to a higher risk


regimen pre-chemo1,3

controlled

continue
current
management

not controlled
delayed nausea and vomiting:
treat for duration of emesis + 1 day3

may increase or change 5-HT3 antagonist (anecdotal evidence)2


and

and
Is patient on highest post-chemo
antiemetic regimen?
no
increase to a higher risk
regimen post-chemo1,3

yes

not
controlled

may add one or more of:


metoclopramide 20-40 mg PO q4-6h1-3
lorazepam 0.5-2 mg PO/SL bid-qid1-3
haloperidol 1-2 mg q4-6h 2
dimenhydrinate 100 mg PO q12h, alternate with
prochlorperazine 10 mg PO q12h (i.e., q6h regimen)3
olanzapine 2.5 5 mg PO BID2
scopolamine 1 patch q72h2
not controlled

controlled

continue
current
management

controlled

consider one or more of3:


nabilone 1 mg PO q12h
behavioural modification
inpatient chemo (monitoring, hydration and
electrolyte replacement prn)
not controlled
may change chemo regimen2,3

BC Cancer Agency - SCNAUSEA Protocol

Page 5 of 6

Warning: The information contained in these documents are a statement of consensus of BC Cancer Agency professionals regarding their views of currently accepted approaches to treatment. Any clinician
seeking to apply or consult these documents is expected to use independent medical judgement in the context of individual clinical circumstances to determine any patient's care or treatment. Use of these
documents is at your own risk and is subject to BC Cancer Agency's terms of use available at www.bccancer.bc.ca/legal.htm

Call Dr. Paul Hoskins or tumour group delegate at (604) 877-6000 or 1-800-6633333 with any problems or questions regarding this treatment program.
Date activated:

4 May 1999

Dated revised:

1 Mar 2012 (addition of fosaprepitant IV, ondansetron QT, olanzapine,


scopolamine, references)

REFERENCES
1. Basch E, Prestrud AA, Hesketh PJ et al. Antiemetics: American Society of Clinical Oncology (ASCO) Clinical
Practice Guideline Update. J Clin Oncol Nov 1 2011; 29(31):4189-98.
2. Ettinger D. NCCN Clinical Practice Guidelines in Oncology - Antiemesis v.1.2012.: National Comprehensive
Cancer Network; 2012.
3. Hoskins P. Antiemetic Guidelines. 2004 October 2004;26:1.
4. Skeel RT editor. Handbook of Cancer Chemotherapy, 6th ed. Philadelphia PA: Lippincott Williams & Wilkins;
2003.
5. McEvoy GK editor. American Hospital Formulary Service 2004. Bethesda: American Society of Health-System
Pharmacists Inc.; 2004.
6. Geling O, Eichler HG. Should 5-hydroxytryptamine-3 receptor antagonists be administered beyond 24 hours after
chemotherapy to prevent delayed emesis? Systematic re-evaluation of clinical evidence and drug cost implications. J
Clin Oncol 2005;23(6):1289-94.
7. Hesketh PJ, Kris MG,Grunberg SM et al. Proposal for classifying the acute emetogenicity of cancer
chemotherapy. J Clin Oncol 1997;15:103-9.
8. The Antiemetic Subcommittee of the Multinational Association of Supportive Care in Cancer (MASCC),. Prevention
of chemotherapy- and radiotherapy-induced emesis: results of the 2004 Perugia International Antiemetic Consensus
Conference. Ann Oncol 2006;17(1):20-8.
9. Grunberg S, Chua D, Maru A et al. Single-dose fosaprepitant for the prevention of chemotherapy-induced nausea
and vomiting associated with cisplatin therapy: Randomized, double-blind study protocol-EASE. J Clin Oncol 2011;
29(11): 1495-1501.
10. Merck Canada Inc. Emend IV (Fosaprepitant) product monograph. Kirkland Quebec; June 10, 2011.
11. Lasseter KC, Gambale J, Jin B, et al.: Tolerability of fosaprepitant and bioequivalency to aprepitant in healthy
subjects. J Clin Pharmacol 2007;47:834-40.
12. Herrington JD, Jaskiewicz AD, Song J: Randomized, placebo-controlled, pilot study evaluating aprepitant single
dose plus palonosetron and dexamethasone for the prevention of acute and delayed chemotherapy-induced nausea
and vomiting. Cancer 2008;112:2080-7.
13. FDA Drug Safety Communication: Abnormal heart rhythms may be associated with use of Zofran (ondansetron)
09-15-2011. Accessed 10 Nov 2011 at:
http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm272041.htm
14. GlaxoSmithKline ondansetron cardiac conduction study at
http://www.gsk-clinicalstudyregister.com/protocol_compounds.jsp
15. US Food and Drug Administration. FDA drug safety communication: abnormal heart rhythms associated with
Anzemet (dolasetron mesylate), 17 Dec 2010. Available at: www.fda.gov/Drugs/DrugSafety/ucm237081. Access 1
Feb 2011.

BC Cancer Agency - SCNAUSEA Protocol

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Warning: The information contained in these documents are a statement of consensus of BC Cancer Agency professionals regarding their views of currently accepted approaches to treatment. Any clinician
seeking to apply or consult these documents is expected to use independent medical judgement in the context of individual clinical circumstances to determine any patient's care or treatment. Use of these
documents is at your own risk and is subject to BC Cancer Agency's terms of use available at www.bccancer.bc.ca/legal.htm