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.
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 PLUS:** dexamethasone 8-12 mg po1-3 PLUS: aprepitant* 125 mg po7-9
aprepitant 80 mg po daily x 2 days2,8,9
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 days1-3OR • metoclopramide 10-40 mg po every 4-6 hours PRN x 3-4 days1-4 High-moderate Low-moderate ONE 5-HT3 ANTAGONIST: • ondansetron 8 mg po • granisetron 1 mg po PLUS: dexamethasone 8-20 mg po1-3 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 days1-3OR • metoclopramide 10-40 mg po every 4-6 hours PRN x 3-4 days1-4 Low PREFERRED: dexamethasone 4-12 mg po1,2 ALTERNATE: prochlorperazine 10 mg po OR metoclopramide 20-40 mg po2
• dexamethasone 4 mg BID for up to 2-3 days1-3OR
• prochlorperazine 10 mg po every 4-6 hours PRN x 3-4 days1-3OR
• metoclopramide 10-40 mg po every 4-6 hours PRN x 3-4 days1-4
Rare Prophylactic treatment not normally required.
• prochlorperazine 10 mg po every 4-6 hours PRN x 3-4 days1-3OR
• 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. *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
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 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
yes
no
Figure 1. SUBSEQUENT ANTIEMETIC REGIMENS AFTER TREATMENT FAILURE
yes no no yes no yes Anxiety or signs of anticipatory nausea and vomiting? Vomited within 24 h of chemo?
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
acute nausea and vomiting: Is patient on highest pre-chemo antiemetic regimen?
not controlled
controlled Vomited > 24 h after
chemo? increase to a higher risk regimen pre-chemo1,3 continue current management and no yes not controlled and controlled not controlled not controlled controlled
delayed nausea and vomiting: treat for duration of emesis + 1 day3
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
consider one or more of3: • nabilone 1 mg PO q12h • behavioural modification
• inpatient chemo (monitoring, hydration and electrolyte replacement prn)
may change chemo regimen2,3 continue
current management increase to a higher risk regimen post-chemo1,3
may increase or change 5-HT3antagonist (anecdotal evidence) 2
Is patient on highest post-chemo antiemetic regimen?
Did patient have ANY nausea or vomiting last cycle? continue current management
Call Dr. Paul Hoskins or tumour group delegate at (604) 877-6000 or
1-800-663-3333 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.
