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www.TheOncologyPharmacist.com Table 4 Updated Guidelines/Recommendations for CINV Emetogenicity NCCN (2010) High Acute Any 5-HT3 RA PLUS dexamethasone PLUS NK-1 RA
ASCO (2006)
MASCC (2010)
Any 5-HT3 RA PLUS dexamethasone PLUS NK-1 RA
Any 5-HT3 RA PLUS dexamethasone PLUS NK-1 RA
Dexamethasone PLUS NK-1 RA
Dexamethasone PLUS NK-1 RA
Dexamethasone PLUS NK-1 RA
Any 5-HT3 RA PLUS dexamethasone PLUS NK-1 RA
Any 5-HT3 RA PLUS dexamethasone
Dexamethasone PLUS NK-1 RA
NK-1 RA
5-HT3 RA PLUS dexamethasone PLUS NK-1 RA NK-1 RA
Any 5-HT3 RA PLUS dexamethasone OPTIONAL NK-1 RA Dexamethasone OR first-generation 5-HT3 RA OR NK-1 RA ± dexamethasone
Any 5-HT3 RA PLUS dexamethasone
5-HT3 (palonosetron preferred) PLUS dexamethasone
Dexamethasone OR 5-HT3 RA
Dexamethasone
Dexamethasone OR metoclopramide OR prochlorperazine
Dexamethasone
Dexamethasone OR 5-HT3 RA OR dopamine antagonist
Delayed
None
None
None
Minimal Acute
No scheduled prophylaxis
No scheduled prophylaxis
No scheduled prophylaxis
Delayed
No scheduled prophylaxis
No scheduled prophylaxis
No scheduled prophylaxis
Delayed AC Regimens Acute Delayed Moderate Acute
Delayed
Low Acute
5-HT3 RA indicates serotonin subtype-3 receptor antagonist; AC, anthracycline plus cyclophosphamide; ASCO, American Society of Clinical Oncology; CINV, chemotherapy-induced nausea and vomiting; MASCC, Multinational Association for Supportive Care in Cancer; NCCN, National Comprehensive Cancer Network; NK-1 RA, neurokinin-1 receptor antagonist. Sources: References 1, 27, and 29.
Several novel delivery systems, including sprays, gels, and dissolving strips, as well as new compounds, are also in development in the United States and Europe (see sidebar). Implications of recent guideline updates for CINV Clinical practice guidelines, including those established by NCCN, ASCO, and MASCC, provide clinicians with valuable evidence-based resources for the management of CINV. The NCCN practice guidelines were updated in April 2010 by a panel of experts that included physicians, pharmacists, and nurses.1 These guidelines are revised as often as several times a year in order to incorporate the latest scientific data. New MASCC practice guidelines also became available earlier this year.27 The ASCO clinical practice guidelines, which were last updated in 2006, are in the process of being revised.28 In addition, the Oncology Nursing Society publishes a resource titled Putting Evidence Into Practice: Evidence-Based Interventions to Prevent, Manage, and Treat Chemotherapy-Induced Nausea and Vomiting.15 Practice guidelines, as well as other CINV-related resources, can be accessed via each of the society’s websites (Table 3). Key recommendations for the treatment of acute and delayed CINV, based on the latest NCCN, ASCO, and MASCC guidelines, are shown in Table 4.1,27,29 All three organizations stress that
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prevention is the overarching goal of antiemesis. Furthermore, they all concur that at biologically equivalent doses, the oral and IV antiemetic formulations have equivalent efficacy.
In its April 2010 guidelines update, NCCN changed the format of the emesis prevention algorithm for MEC by separating day 1 from days 2 and 3. For acute CINV in patients receiving both HEC and MEC, the combination of a 5-HT3 RA, dexamethasone, plus an NK-1 RA is recommended (aprepitant or fosaprepitant is specified in the MASCC and NCCN guidelines). To prevent delayed CINV in patients receiving HEC, the MASCC, NCCN, and ASCO guidelines all recommend dexamethasone plus aprepitant. To prevent delayed CINV in patients receiving a combination of anthracycline plus cyclophosphamide (AC regimen), the guidelines from all 3 societies recommend treatment with aprepitant. The 2010 version of the MASCC guidelines includes the following changes27,30: • For acute CINV in patients receiving non-AC regimens of MEC, palonosetron is specifically recom-
mended, with dexamethasone. The previous MASCC guidelines (2008 version) included a general 5-HT3 RA recommendation plus dexamethasone. • In patients with delayed CINV receiving an AC regimen, aprepitant alone is recommended. The 2008 guidelines recommended aprepitant or dexamethasone. • For acute CINV in patients receiving AC regimens, a 5-HT3 RA with dexamethasone and aprepitant or fosaprepitant is recommended. If aprepitant is not available, palonosetron plus dexamethasone is recommended. In addition, in its April 2010 guidelines update, NCCN changed the format of the emesis prevention algorithm for MEC by separating day 1 from days 2 and 3.1 Future directions and ongoing challenges The guidelines for preventing and treating CINV represent valuable clinical tools for implementing evidencebased practices. Application of these guidelines must be accompanied by accurate patient self-assessment of symptoms throughout the duration of CINV risk.5 It is important for clinicians to ask patients the appropriate questions and provide them with the most effective assessment tools. In addition, there is an ongoing need for better strategies to monitor patients more closely after
they leave the clinic. In the future, research will likely focus on topics such as CINV induced by high-dose chemotherapy; the prevention of cisplatin-induced delayed CINV; and better control of nausea—an important emetogenic challenge that is a different phenomenon than vomiting.30 Further studies are also needed to address current guideline limitations with respect to multiday chemotherapy regimens, combination chemotherapy, and patients who do not respond to initial antiemetic regimens. Nevertheless, based on the evidence, knowledge, and clinical judgment factored into these guidelines, adherence is a worthy attempt to deliver optimal patient care.10 Clinicians must continue to advocate for patients to ensure they receive the most effective antiemetic agents during the appropriate therapeutic window. They must also work with patients to address any cost or reimbursement issues that present barriers to treatment. Conclusion CINV is preventable in the majority of patients receiving chemotherapy.12 How ever, improved therapeutic interventions are needed, particularly for patients with delayed CINV. Ideally, an antiemetic therapy should provide adequate protection for the patient throughout the anticipated period of nausea and vomiting.5,14 Barriers to the optimal treatment of CINV are surmountable when Continued on page 14
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