Anti-Nausea Drugs for Chemotherapy Patients
Nausea is one of the most common and most difficult aspects of chemotherapy for cancer patients. Nausea can have secondary effects on cancer patients by interfering with their eating habits during and immediately after chemotherapy.
Drugs to mitigate chemotherapy-induced nausea include Kytril, Megace, and Zofran. The high cost of some of these drugs has kept many cancer patients not covered by insurance from obtaining one of these potentially beneficial drugs. If you are receiving chemotherapy and are experiencing nausea, you should be able to demand that any HMO, PPO, or insurance carrier pay for this class of drug. These drugs may enable a cancer patient to tolerate chemotherapy long enough for it to be effective.
An interesting study evaluated glutathione and vitamins C and E for their antinausea properties. Glutathione and vitamins C and E significantly reduced cisplatin-induced vomiting in dogs. The anti-nausea activity of antioxidants was attributed to their ability to react with free radicals generated by cisplatin. Ginger extract has also been shown effective in reducing nausea symptoms (Keating et al. 2002).
Aprepitant (Emend®) for Chemotherapy-Induced Nausea and Vomiting
Chemotherapy-induced acute and delayed nausea and vomiting (CINV) can occur with either an initial chemotherapy cycle or with repeated chemotherapy cycles. Cisplatin is a commonly used chemotherapy drug known to cause CINV in most patients who receive it. Cisplatin is used to slow or stop cancer cell growth in patients with metastasized testicular and ovarian tumors who have already had surgical and/or radiotherapy procedures. It is used in patients with metastasized ovarian tumors who are unresponsive to standard chemotherapy, but have not yet received cisplatin.
Patients with advanced transitional-cell bladder cancer that is no longer controlled by surgery and/or radiotherapy also receive cisplatin. The drug is given intravenously in cycles, often in combination with other chemotherapy drugs. Severe CINV usually occurs within 1 to 4 hours after administration and symptoms can continue for 24 hours or persist for up to a week. A delayed form can occur in patients who had no nausea when cisplatin was initially administered. This form begins 24 hours or more following cisplatin chemotherapy. The symptoms of cisplatin CINV are so debilitating that some patients refuse further chemotherapy treatment.
On March 26, 2003, aprepitant (Emend®) received FDA approval. Aprepitant is a drug to be used in combination with other anti-nausea/anti-vomiting drugs to prevent CINV. Standard anti-nausea therapy for CINV is dexamethasone (Decadron®, a corticosteroid) and ondansetron (Zofran®, a 5-HT3 or serotonin receptor antagonist). However, aprepitant works in combination with these anti-nausea drugs by targeting a different family of receptors in the brain associated with nausea called the NK1 receptors (neurokinin 1). A typical combination treatment regimen directed by a treating physician is:
- Day 1: 125 mg of aprepitant orally 1 hour before chemotherapy; 32 mg of ondansetron intravenously before chemotherapy; and 12 mg of dexamethasone orally.
- Days 2 through 4: 80 mg of aprepitant orally on days 2 and 3 only; and 8 mg of dexamethasone orally in the morning on days 2 to 4.
Aprepitant (Emend) is the first NK1 blocking drug to be approved by the FDA. FDA approval was based on the results of studies including over 1000 cancer patients who received chemotherapy that caused CINV (de Wit et al. 2003; Heskith et al. 2003; Poli-Bigelli et al. 2003). In these studies, when compared to symptoms in patients who received standard CINV medicines, the symptoms of CINV were reduced significantly when aprepitant was included with the standard medicines.
In a Phase III study (520 patients; multicenter, randomized, double-blind, placebo-controlled; endpoint of complete response) that evaluated patients for 5 days after chemotherapy, 72.7% of the patients using aprepitant had complete response on days 1 to 5 (no nausea and vomiting; no rescue therapy). This response was significantly higher than the 52.3% response in the standard therapy group (Hesketh et al. 2003). A similar Phase III study evaluated 523 patients for efficacy and 568 patients for safety for 5 days following high-dose cisplatin chemotherapy. During the 5 days after chemotherapy, patients in the aprepitant group had a complete response of 62.7% vs. 43.3% in the standard therapy group. Incidence of adverse events was similar in both groups (72.8% vs. 72.6%). In the aprepitant group, complete response ranged from 82.8% on day 1 to 62.7% on days 2 to 5 vs. 68.4% on day 1 and 46.8% on days 2 to 5 for the standard therapy group (Poli-Bigelli et al. 2003).
Another Phase III double-blind study (endpoint of complete response) enrolled 202 patients and observed them for 6 chemotherapy cycles. The group receiving aprepitant (125 mg before cisplatin and 80 mg on days 2 to 5 vs. 375 mg/250 mg) reported a complete response of 64% vs. 49% for the group receiving standard ondansetron/dexamethasone treatment. After cycle 6, the aprepitant group still had a complete response of 59% compared to 35% in the standard therapy group (de Wit et al. 2003). Researchers conducting these three studies concluded that aprepitant plus a standard regimen of odansetron and dexamethasone consistently provided superior protection from CINV compared to standard therapy alone (de Wit et al. 2003; Heskith et al. 2003; Poli-Bigelli et al. 2003). Additionally, de Wit et al. (2003) concluded that aprepitant provided sustained protection against CINV over multiple cycles of chemotherapy when existing drugs often become less effective.
A multi-center, randomized, double-blind, placebo-controlled study seeking to define the most appropriate dose regimen of oral aprepitant (375 mg/250 mg vs. 125 mg/80 mg vs. 40 mg/25 mg vs. standard therapy) was conducted in 376 patients with cancer who were receiving initial cisplatin. (While the study was ongoing, aprepitant 375 mg/250 mg was discontinued resulting from pharmacokinetic data obtained that indicated an apparent interaction with dexamethasone.) The authors concluded that an aprepitant 125-mg/80-mg regimen added to a standard regimen of intravenous ondansetron and oral dexamethasone had the most favorable benefit to risk profile (Chawla et al. 2003). Possible drug interactions with aprepitant include some chemotherapies, birth control pills (reduces effectiveness), blood thinners (Coumadin), and other drugs (e.g., Orap®, Seldane®, Hismanal®, and Propulsid®) as well as non-prescription and herbal products (Merck 2003).