Guidelines for Prevention and Treatment of Chemotherapy-Induced Nausea and Vomiting in Adults Protocol Code Tumour group Physician Contact SCNAUSEA SUPPORTIVE CARE Dr. Paul Hoskins ELIGIBILITY Adults receiving chemotherapy. Drug acquisition: Antiemetics are considered supportive treatment. These agents are t BCCA benefit drugs and are t 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 t intended to replace the clinical judgment of individual practitioners caring for individual patients. BC Cancer Agency - SCNAUSEA Protocol Page 1 of 6
PROPHYLACTIC ANTIEMETIC REGIMENS For multiple days of chemotherapy, repeat antiemetics before each treatment. EMETOGENICITY PRE-CHEMOTHERAPY POST-CHEMOTHERAPY High ONE 5-HT 3 ANTAGONIST: aprepitant 80 mg po daily x 2 days 2,8,9 ondansetron 8 mg po granisetron 1 mg po High-moderate Low-moderate Low Rare PLUS:** dexamethasone 8-12 mg po 1-3 PLUS: aprepitant* 125 mg po 7-9 ONE 5-HT 3 ANTAGONIST: ondansetron 8 mg po granisetron 1 mg po PLUS: dexamethasone 8-20 mg po 1-3 PREFERRED: dexamethasone 4-12 mg po 1,2 ALTERNATE: prochlorperazine 10 mg po OR metoclopramide 20-40 mg po 2 Prophylactic treatment t rmally required. For prophylaxis after prior treatment failures, refer to Figure 1. PLUS:** dexamethasone 4 mg po evening of chemo, 3 then 4 mg po BID x 2-5 days 2,3 AND ONE ANTIEMETIC AS-NEEDED : dexamethasone 4 mg po evening of chemo, 3 then 4 mg po BID x 2-3 days 2,3 AND ONE ANTIEMETIC AS-NEEDED : dexamethasone 4 mg BID for up to 2-3 days 1-3 OR *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 mg 11 which seems sufficient to cover days 2 and 3 12 ) **If patients do t receive aprepitant /fosaprepitant, may increase dexamethasone to 20 mg day 1 and 16 mg BID days 2 to 4 1 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-HT 3 antagonists are as effective as multiple doses. 3,5 Currently available 5-HT 3 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 Page 2 of 6
using medications that prolong QT interval. ECG monitoring is recommended in patients with electrolyte abrmalities, 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 t 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 role for the routine use of 5-HT 3 antagonists more than 24 hours after chemotherapy. 1-3,6 DETERMINING EMETOGENICITY OF CHEMOTHERAPY Emetogenicity: percentage of patients who will experience emesis if t 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 t specified, consult Cancer Drug Manual. o Treat for the most emetogenic agent 1 OR use Hesketh Algorithm. HESKETH ALGORITHM 7 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 t 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 gastritis 1 o medications (pain meds, bronchodilators) 1,2 o brain metastases 1,2 o vestibular dysfunction 2 o electrolyte imbalance, 2 uremia 2 o infection 1 2. Control this episode of nausea and vomiting. Approach to treatment 2 : 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 Page 3 of 6
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 t previously given 2 o prochlorperazine 25 mg pr q12h or 10 mg po/iv q4-6h 2 o metoclopramide 20-40 mg po q4-6h or 1-2 mg/kg iv q3-4h ± diphenhydramine 25-50 mg po/iv q4-6h 2 o lorazepam 0.5-2 mg po or sl q4-6h 2 o haloperidol 1-2 mg po q4-6h or 1-3 mg iv q4-6h 2 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 Page 4 of 6
Figure 1. SUBSEQUENT ANTIEMETIC REGIMENS AFTER TREATMENT FAILURE Did patient have ANY nausea or vomiting last cycle? continue current management Anxiety or signs of anticipatory nausea and vomiting? continue optimal prophylactic regimen and add one or more of: lorazepam 0.5-2 mg PO/SL q12h, start the night before chemo 2,3 behavioural therapy (e.g., relaxation, hypsis, music therapy) 1-3 Vomited within 24 h of chemo? acute nausea and vomiting: Is patient on highest pre-chemo antiemetic regimen? Vomited > 24 h after chemo? delayed nausea and vomiting: treat for duration of emesis + 1 day 3 and Is patient on highest post-chemo antiemetic regimen? increase to a higher risk regimen post-chemo 1,3 continue current management increase to a higher risk regimen pre-chemo 1,3 t t continue current management may increase or change 5-HT 3 antagonist (anecdotal evidence) 2 and may add one or more of: metoclopramide 20-40 mg PO q4-6h 1-3 lorazepam 0.5-2 mg PO/SL bid-qid 1-3 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 BID 2 scopolamine 1 patch q72h 2 t consider one or more of 3 : nabilone 1 mg PO q12h behavioural modification inpatient chemo (monitoring, hydration and electrolyte replacement prn) t may change chemo regimen 2,3 BC Cancer Agency - SCNAUSEA Protocol Page 5 of 6
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 mograph. 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-, pilot study evaluating aprepitant single dose plus palosetron and dexamethasone for the prevention of acute and delayed chemotherapy-induced nausea and vomiting. Cancer 2008;112:2080-7. 13. FDA Drug Safety Communication: Abrmal 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: abrmal 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 Page 6 of 6