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Implications of Recent Guideline Updates on the Management of Chemotherapy-induced Nausea and Vomiting the appropriate proactive steps are taken. Strategies for improving control of CINV include selecting the most effective therapy, integrating evidencebased guidelines into everyday practice, and using tools and resources to closely monitor patients concerning the intensity and duration of their symptoms. Moreover, it is important for clinicians to remain current on updates to the clinical practice guidelines. ● Loretta Fala assisted in the development of this article. References 1. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology™. Antiemesis, V.2.2010. April 7, 2010. http://www.nccn.org/profession als/physician_gls/PDF/antiemesis.pdf. Accessed August 6, 2010. 2. Hesketh PJ. Chemotherapy-induced nausea and vomiting. N Engl J Med. 2008;358(23):2482-2494. 3. Hawkins R, Grunberg S. Chemotherapy-induced nausea and vomiting: challenges and opportunities for improved patient outcomes. Clin J Oncol Nurs. 2009;13(1):54-64. 4. Grunberg SM, Deuson RR, Mavros P, et al. Incidence of chemotherapy-induced nausea and emesis after modern antiemetics. Cancer. 2004;100(10):2261-2268. 5. Wickham R. Best practice management of CINV in oncology patients: II. Antiemetic guidelines and ration-
ale for use. J Support Oncol. 2010;8(2 suppl 1):10-15. 6. Ballatori E, Roila F, Ruggeri B, et al. The impact of chemotherapy-induced nausea and vomiting on healthrelated quality of life. Support Care Cancer. 2007;15 (20):179-185. 7. Shih Y-CT, Xu Y, Elting LS. Costs of uncontrolled chemotherapy-induced nausea and vomiting among working-age cancer patients receiving highly or moderately emetogenic chemotherapy. Cancer. 2007;110 (3):678-685. 8. Burke TA, Wisniewski T, Ernst FR. Resource utilization and costs associated with chemotherapy-induced nausea and vomiting (CINV) following highly or moderately emetogenic chemotherapy administered in the US outpatient hospital setting [published online ahead of print January 26, 2010]. Support Care Cancer. 9. Vanscoy GJ, Fortner B, Smith R, et al. Preventing chemotherapy-induced nausea and vomiting: the economic implications of choosing antiemetics. Community Oncol. 2005;2(2):127-132. 10. Grunberg SM. Obstacles to the implementation of antiemetic guidelines. J Natl Comp Cancer Network. 2009;7(5):601-605. 11. Ettinger DS. Nausea and vomiting with multi-day chemotherapy. From: Recent advances in the management of chemotherapy-induced nausea and vomiting: a case study compendium. Clinical Advances in Hematology & Oncology. 2010;8(5)(suppl 9):12-14. 12. Hesketh P. Penny wise, dollar foolish approach to antiemetic use may compromise patient care. American Society of Clinical Oncology. September 2009. http://jop. ascopubs.org/content/5/5/221.full.pdf. Accessed August 9, 2010. 13. Wiser W, Berger A. Practical management of chemotherapy-induced nausea and vomiting. Oncology. 2005; 19(5):637-645.
14. Georgy A, Neceskas J, Goodin S. Antiemetic treatment in patients with breast cancer: focus on drug interactions and safety concerns. Am J Health Syst Pharm. 2007;64(21):2227-2236. 15. Tipton JM, McDaniel RW, Barbour L, et al. Putting evidence into practice: evidence-based interventions to prevent, manage, and treat chemotherapy-induced nausea and vomiting. Clin J Oncol Nurs. 2007;11(1):69-78. 16. Schwartzberg LS. Chemotherapy-induced nausea and vomiting: which antiemetic for which therapy? Oncology (Williston Park). 2007;21(8):946-953. 17. Michaud LB. Controlling chemotherapy-induced nausea and vomiting—a new antiemetic delivery system. HemOnc Today Website. Epub March 25, 2009. http:// www.hemonctoday.com/article.aspx?rid=38195. Accessed August 7, 2010. 18. Hatoum HT, Lin S, Buchner D, Cox D. Chemotherapy-induced nausea and vomiting-associated hospital and ER visits in real-world practice: palonosetron versus other 5-HT3-RA anti-emetic regimens. J Clin Oncol. 2010;28(15 suppl). Abstract 9127. 19. Navari RM. Palonosetron for the prevention of chemotherapy-induced nausea and vomiting in patients with cancer. Future Oncol. 2010;6(7):1073-1084. 20. Emend® capsules [package insert]. Whitehouse Station, NJ: Merck & Co, Inc; 2010. 21. Gralla RJ, Rapoport BL, Jordan K, et al. Assessing the magnitude of antiemetic benefit with the addition of the NK1 receptor antagonist (NK1) aprepitant for all platinum agents: analysis of 1,872 patients in prospective randomized clinical phase III trials (RCTs). J Clin Oncol. 2010;28(15 suppl). Abstract 9057. 22. Pflederer C, Goodgame BW, Morgensztern D, et al. A prospective study on the incidence of delayed nausea and vomiting following administration of carboplatincontaining regimens for treatment of cancer without
prophylactic aprepitant. J Clin Oncol. 2010;28(15 suppl). Abstract e19552. 23. Gilmore JW, Feinberg BA, Wisniewski T, et al. Risk factors for nausea and vomiting (NV) following highly or moderately emetogenic chemotherapy (HEC or MEC) in U.S. community oncology practice. J Clin Oncol. 2010;28(15 suppl). Abstract e19531. 24. Navari RM, Einhorn LH, Passik SD, et al. A phase II trial of olanzapine for the prevention of chemotherapy-induced nausea and vomiting: a Hoosier Oncology Group study. Support Care Cancer. 2005;13(7):529-534. 25. Lohr L. Chemotherapy-induced nausea and vomiting. Cancer J. 2008;14(2):85-93. 26. National Institutes of Health. CINV clinical studies—gabapentin. ClinicalTrials.gov. http://clinicaltrials. gov/ct2/show/NCT00880191?term=gabapentin+ANd+ CINV&rank=1. Accessed August 10, 2010. 27. Multinational Association of Supportive Care in Cancer. Antiemetic Guidelines (English). Updated April 2010. www.mascc.org/mc/page.do?sitePageId=88041. Accessed August 10, 2010. 28. American Society of Clinical Oncology (ASCO). Original guidelines and guideline updates in progress. Updated October 6, 2009. www.asco.org/ASCO/Down loads/Cancer%20Policy%20and%20Clinical%20Affairs /Clinical%20Affairs%20%28derivative%20prod ucts%29/Guidelines%20in%20Progress%2010.6.09.pdf. Accessed August 11, 2010. 29. Kris MG, Hesketh PJ, Somerfield MR, et al. American Society of Clinical Oncology Guideline for Antiemetics in Oncology: update 2006. J Clin Oncol. 2006;24:2932-2947. 30. Roila F, Herrstedt J, Aapro M, et al. Guideline update for MASCC and ESMO in the prevention of chemotherapy- and radiotherapy-induced nausea and vomiting: results of the Perugia consensus conference. Ann Oncol. 2010;21(suppl 5):v232-v243.
COMMENTARY
Improving Outcomes for Chemotherapyinduced Nausea and Vomiting: A Pharmacist’s Perspective By Sally Barbour, PharmD, BCOP, CPP Duke Comprehensive Cancer Center, Durham, North Carolina
C
hemotherapy-induced nausea and vomiting (CINV) is still one of the most dreaded side effects of systemic cancer treatment and is a cause of great distress for numerous patients.1 Nausea, specifically, remains a symptom that is often ranked high on the list of patient concerns related to their treatment. In a recent survey of women receiving cisplatin-based chemotherapy for gynecologic malignancies, the potential of uncontrolled CINV ranked just above death.2 Although we have witnessed significant advances in the prevention and management of CINV over the past 10 years, some patients still experience symptoms. Etiology/pathophysiology of CINV Recent insights into the causes of nausea and vomiting have led to the development of novel antiemetic agents and a more comprehensive approach to prevention and treatment. The etiology of CINV is multifactorial, and is the end result of a complex network of pathways,
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neurotransmitters, and receptors. It follows that the most effective approach to the management of CINV is to utilize agents with different mechanisms of action that can target these various areas. There are three main components to the emetic reflex: the emetic or vomit-
Recent insights into the causes of nausea and vomiting have led to the development of novel antiemetic agents.
ing center; the chemoreceptor trigger zone (CTZ); and visceral afferent nerve fibers of the small intestine. The vomiting center is not an anatomically distinct area, but rather several regions in the brainstem that coordinate input from multiple sources, such as the gas-
trointestinal tract, the cortical system, and the CTZ (Figure). Upon receiving this input, the vomiting center activates the salivary receptors, respiratory center, and vasomotor centers, as well as the cranial nerves. These areas provide the final efferent output to the abdominal muscles, stomach, diaphragm, and esophagus, resulting in emesis. The second component of the emetic reflex, the CTZ, is located in the area postrema in the floor of the fourth ventricle. Located outside of the blood– brain barrier, the CTZ can detect toxins in the blood, such as chemotherapeutic agents. The third component, visceral afferent nerve fibers, originate from the small intestine. These appear to have the greatest role in CINV, and a variety of receptors, including serotonin subtype-3 (5-HT3) and neurokinin-1 (NK1) receptors, are located on their terminal ends.3-5 Serotonin receptors, which are located both centrally and peripherally, have been shown to play a key role in the
modulation of acute CINV. NK-1 receptors, which are widely distributed throughout the central nervous system, as well as in peripheral sites such as the gastrointestinal tract, also play a significant role, especially in the delayed phase of CINV.4,6 Therefore, some of the most effective agents currently being used in the prevention and treatment of CINV target these receptors. The evolving role of 5-HT3 receptor antagonists The development of 5-HT3 receptor antagonists (RAs) has had a significant impact on the management of CINV, and the utility of these agents has been demonstrated in patients receiving numerous types of chemotherapy regimens.7-10 Currently, there are four 5-HT3 RAs available for use in the United States: the first-generation agents, dolasetron, ondansetron, and granisetron, and the second-generation agent, palonosetron. These drugs have minimal toxicities when used at recom-
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