Combination Antiemetic Regimens
Table 3 summarizes recommended antiemetic regimens, according to the emetic potential of the chemotherapy regimen.
Serotonin Antagonist Plus Dexamethasone(Drug information on dexamethasone)
Combinations of a 5-HT3 antagonist and dexamethasone form the basis of the most effective regimens for controlling acute chemotherapy-induced emesis. Use of these two agents combined has proved to be more effective than either agent alone. Addition of an NK1 antagonist results in increased activity against highly emetogenic chemotherapy. However, inhibition by aprepitant or fosaprepitant of the cytochrome P-450 3A4 metabolic pathway may require a decrease in the dose of concomitantly administered dexamethasone.
Sidebar: Olanzapine is an antipsychotic agent that blocks numerous neurotransmitter receptors. Recent work has suggested that olanzapine may have efficacy as part of a combination regimen to prevent delayed emesis or as an agent for the treatment of breakthrough emesis after highly emetogenic chemotherapy. Particular activity against nausea has been seen (Navari RM et al: J Clin Oncol 30(15s):abstract 9064, 2012).
Treatment of Emesis
Acute Emesis
Antiemetic regimens for acute emesis, by emetic riskA management strategy to prevent acute chemotherapy-induced emesis is outlined in Table 3. All patients should receive education and reassurance, as well as antiemetics tailored to the chemotherapy regimen. For regimens that commonly cause emesis (> 30%), antiemetic combinations are recommended; for regimens of low risk (10% to 30% incidence), a single agent will usually suffice. As stated in Table 3, chemotherapy of minimal risk typically does not require preventive treatment.
Delayed Emesis
Delayed emesis is defined as nausea or vomiting beginning or persisting 24 hours or more after chemotherapy administration. The pathophysiology of this problem is unclear, but it is particularly common after high-dose cisplatin (≥ 50 mg/m2), carboplatin (≥ 300 mg/m2), cyclophosphamide(Drug information on cyclophosphamide) (≥ 600 mg/m2), or doxorubicin(Drug information on doxorubicin) (≥ 50 mg/m2).
In one natural history study, 89% of patients experienced some delayed emesis from 24 to 120 hours after receiving high-dose cisplatin(Drug information on cisplatin), with a peak incidence occurring between 48 and 72 hours. With anthracyclines or cyclophosphamide, the rate of delayed emesis without preventive antiemetics is about 30%.
Some observations suggest that delayed emesis may begin earlier. When combination antiemetic regimens for acute emesis "fail," the initial emetic episode is often at 17 to 23 hours following chemotherapy. In some trials, antiemetics to prevent delayed emesis have been initiated at 16 to 17 hours.
Treatment options
The combination of dexamethasone and an NK1 antagonist has demonstrated efficacy. Activity of palonosetron(Drug information on palonosetron) may also continue for several days. The recommended doses and schedules for the prevention of delayed emesis are given in Table 4.
Treatment regimens for prevention of delayed emesisAnticipatory Emesis
This problem is defined as nausea or vomiting beginning before the administration of chemotherapy in patients with poor emetic control during previous chemotherapy. Because this problem is a conditioned response, the hospital environment or other treatment-related associations may trigger the onset of emesis unrelated to chemotherapy. Strong emetic stimuli combined with poor emetic control increase the likelihood that anticipatory emesis will occur.
Treatment approach
Behavioral therapy involving systematic desensitization can be helpful in managing anticipatory emesis. Also, benzodiazepines appear to be useful. However, the best approach to anticipatory emesis is prevention of prior emesis, which underscores the need to provide the most effective and appropriate antiemetic regimens with the initial course of emesis-producing chemotherapy.
Radiation-induced nausea and vomiting
Emetogenicity of radiation therapy is dependent on anatomic site and dose. For example, total body irradiation is highly emetogenic, while upper abdominal irradiation is moderately emetogenic. Serotonin antagonists remain the mainstay of antiemetic therapy for highly or moderately emetogenic radiotherapy.
