Updates in CINV Including NCCN Guideline Revisions

In our last issue, we published a review of treatment options for acute and delayed chemotherapy-induced nausea and vomiting. Since then, a few things have happened on this front. In March, the National Comprehensive Cancer Network (NCCN) updated its “Antiemesis Guidelines,” releasing Version 2.2010. In addition to updating the “Discussion” section, the NCCN changed the structure for preventing emesis in patients receiving chemotherapy with a moderate emetic risk, separating day 1 from days 2 and 3. A more substantive edit of the guidelines occurred in January 2010 (v. 1.2010). At that time, NCCN added romidepsin to the list of intravenous drugs with low emetic risk. Estramustine was added as an oral agent for which antiemetic prophylaxis is now recommended, and the newly approved drug pazopanib (Votrient) was added to the list of oral agents for which antiemetic agents should be administered as needed. The panel also added a statement on breakthrough treatment, noting that “some patients may require several agents utilizing different mechanisms of action.”

The new NCCN guidelines are available at the Website, at www.nccn.org. The Multinational Association of Supportive Care in Cancer held a workshop on updating its antiemetic guidelines at its latest annual meeting in June 2009. The group expects to put the new guidelines on its Website,www.mascc.org, next month. The FDA approved generic orally disintegrating ondansetron tablets to prevent CINV. The drug is not approved for delayed emesis. Another manufacturer received FDA approval to market a generic injectable form of ondansetron. An Indian company was granted FDA approval to sell different doses of injectable granisetron, another 5-HT₃antagonist. NCCN guidelines include ondansetron and granisetron in the list of drug options for preventing acute emesis, but the panel states that these agents are less effective at preventing delayed emesis.

The guidelines note that “intravenous palonosetron (Aloxi) is superior to other 5-HT₃antagonists for preventing delayed nausea”; this is likely because it has a binding affinity for 5-HT₃that is 100 times greater than the other 5-HT₃antagonists and has a significantly longer half life (approximately 40 hours). Palonosetron is the only FDA-approved 5-HT₃antagonist approved to treat delayed-onset CINV.

A.P. Pharma had applied to the FDA for approval of its novel injectable drug APF530, a long-acting form of granisetron, to treat acute and delayed chemotherapy-induced emesis, but the FDA rejected the application last month, citing multiple issues. The agency asked for reanalysis of the trial data submitted with the application, expressed concerns about certain aspects of the dosing system, and questioned whether the complicated two-syringe delivery system could result in improper administration. The FDA also identified deficiencies at the company’s manufacturing facility. The company plans to meet with the FDA on how to resolve the issues but stated the drug would definitely not come to market in 2010.

Palonosetron, which has long been approved in the United States to treat acute and delayed CINV, recently launched in Japan, following regulatory approval in January 2010. Japan is the 63^rd country to approve palonosetron.