Nausea and Vomiting in Cancer Patients

Orlando—When cancer patients undergo chemotherapy treatments, they face numerous challenges, among them nausea and vomiting. Physicians and nurses sometimes underestimate how many patients will have these side effects, according to Charles Loprinzi, MD, professor of breast cancer research at the Mayo Clinic.

At the Spring Managed Care Forum, Dr. Loprinzi discussed the seriousness of nausea and vomiting and how patients can deal with these side effects in a session titled Chemotherapy-Induced Nausea and Vomiting (CINV): Perceptions, Mechanisms, and Treatment Guidelines.

Dr. Loprinzi said there are 3 classifications of CINV: (1) acute, which occurs up to 24 hours after chemotherapy; (2) delayed, which occurs between 24 and 120 hours after chemotherapy; and (3) anticipatory, which occurs prior to chemotherapy. Risk factors associated with CINV include younger age (<50 years), female sex, no or minimal prior history of alcohol use, prior CINV, anxiety, a history of morning sickness or motion sickness, a high dose of chemotherapy, and a rapid infusion rate of chemotherapy.

Dr. Loprinzi noted studies that indicated patients perceived nausea as the most severe side effect of chemotherapy. He also cited an international observational study of 298 patients at 14 practices that found physicians and nurses underestimated the number of chemotherapy patients who would experience nausea and vomiting.

The clinicians predicted 24% of patients with moderately emetogenic chemotherapy would have acute nausea, but 37% ended up having acute nausea. Meanwhile, they predicted 13% would have acute vomiting (13% did), 24% would have delayed nausea (52% did), and 15% would have delayed vomiting (28% did).

The physicians and nurses predicted 34% of patients with highly emetogenic chemotherapy would have acute nausea (33% did), 17% would have acute vomiting (12% did), 39% would have delayed nausea (60% did), and 22% would have delayed vomiting (50% did).

Dr. Loprinzi said the approach to controlling nausea and vomiting should focus on prevention rather than treatment. Some therapeutic options to prevent nausea and vomiting are dexamethasone (a corticosteroid), aprepitant (a neurokinin-1 receptor antagonist), lorazepam (a benzodiazepine), dronabinol (a cannabinoid), and 5-HT₃ receptor agonists such as ondansetron, granisetron, dolasetron, and palonosetron. Dr. Loprinzi said that when 5-HT₃ receptor agonists were introduced, they represented an improvement over other treatments. They are typically used in combination with dexamethasone and are effective at reducing acute vomiting, but they have variable efficacy in delaying events, according to Dr. Loprinzi.

In a trial of patients who received chemotherapy, those who took 0.25 mg of palonosetron intravenously (n=189) had a better response to the medication (defined as no nausea or vomiting and no rescue therapy) compared with those who took 32 mg of ondansetron intravenously (n=185). During the first day following chemotherapy, 81.0% of patients in the palonosetron group had a complete response compared with 68.6% of patients in the ondansetron group (P<.025). During days 2 through 5 following chemotherapy, 74.1% of patients in the palonosetron group had a complete response compared with 55.1% of patients in the ondansetron group (P<.025). The overall complete response rates were 69.3% of the palonosetron group and 50.3% of the ondansetron group (P<.025).

The time to treatment failure (defined as the time to the first nausea or vomiting episode or the use of rescue medication) was significantly superior in the palonosetron group after 5 days (P=.0003). Of the patients in the trial, 72% were female and the majority received cyclophosphamide and/or doxorubicin combination therapy for breast cancer. They had no concomitant dexamethasone pretreatment.

Next, Dr. Loprinzi discussed a meta-analysis of 32 studies involving 5613 patients who received dexamethasone for acute and delayed CINV. The study found dexamethasone was effective for both versions of CINV. Another trial concluded that 8 mg of ondansetron administered intravenously in combination with various doses of dexamethasone had similar efficacy in treating acute and delayed CINV. The regimens included 8 mg of dexamethasone administered intravenously on day 1 and then 4 mg of dexamethasone administered orally on days 2 through 5; 24 mg of dexamethasone administered intravenously on days 1 through 5; and 8 mg of dexamethasone administered intravenously on days 1 through 5. At least 80% of patients in each group had complete control.

Aprepitant is another effective treatment for CINV, according to Dr. Loprinzi. In 2 trials involving 1043 patients, 86% of those taking aprepitant plus cisplatin had a complete response during the first day after chemotherapy compared with 73% of patients in the standard treatment group (P<.001). In addition, 72% of patients taking aprepitant plus cisplatin had a complete response during days 2 through 5 after chemotherapy compared with 52% of patients in the standard treatment group (P<.001). Overall, 68% of patients in the aprepitant plus cisplatin group had a complete response compared with 47% of patients in the standard treatment group (P<.001). The authors defined complete response as no nausea and vomiting and no rescue medication.

Meanwhile, a phase 3, randomized, double-blind study found that a single-dose intravenous fosaprepitant regimen was similar in efficacy compared with a 3-day, oral aprepitant regimen. A complete response was found in 71.9% of patients in the fosaprepitant group and 72.3% of patients in the aprepitant group. During the acute phase, 89.0% of patients in the fosaprepitant group and 88.0% of patients in the aprepitant group had a complete response, whereas during the delayed phase, 74.3% of patients in the fosaprepitant group and 74.2% of patients in the aprepitant group had a complete response.

Dr. Loprinzi then discussed guidelines from the American Society of Clinical Oncology (ASCO) regarding the use of these medications. ASCO recommends patients at high risk of nausea and vomiting (defined as a >90% risk) should take a 5-HT₃ receptor agonist plus dexamethasone plus aprepitant for acute prevention and dexamethasone plus aprepitant for delayed prevention. Patients at moderate risk (defined as between 30% and 90% risk) should take a 5-HT₃ receptor agonist plus dexamethasone for acute prevention and oral dexamethasone or a 5-HT₃ receptor agonist for delayed prevention. Patients at low risk (defined as between 10% and 30% risk) are advised to take dexamethasone for acute prevention, but they do not have to take anything for delayed prevention, according to the guidelines. There are no preventive measures for patients who have a <10% risk of nausea or vomiting.

Although the newer drugs are effective, they are also more expensive than older regimens, according to Dr. Loprinzi. For instance, a 1-mg tab of granisetron costs $8 for non-Medicare plans and $0.77 for Medicare plans (with Medicare patients responsible for $0.15), while a 4-mg tab of dexamethasone costs $1 for non-Medicare and Medicare plans (with Medicare patients responsible for $0.20).