Management of Nausea and Vomiting

Combination antiemetic regimens

Table 3 summarizes recommended antiemetic regimens, according to the emetic potential of the chemotherapy regimen.

Serotonin antagonist plus 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 acute cisplatin(Drug information on cisplatin)-induced emesis. However, inhibition by aprepitant or fosaprepitant of the CYP3A4 metabolic pathway may require a decrease in the dose of concomitantly administered dexamethasone.

Treatment of emesis

Acute emesis

TABLE 3Antiemetic regimens for acute emesis, by emetic risk

A 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 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, 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 oral dexamethasone and metoclopramide(Drug information on metoclopramide) has been found to be superior to dexamethasone alone or placebo in a double-blind, randomized trial. 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.

Anticipatory emesis

TABLE4Treatment regimens for prevention of delayed emesis

This problem is defined as nausea or vomiting beginning before the administration of chemotherapy in patients with poor emetic control during previous chemotherapy. As 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, which underscores the need to provide the most effective and appropriate antiemetic regimens with the initial course of emesis-producing chemotherapy.