Table 2. Comparison of Aprepitant and Standard Regimens continued...
A randomized phase III trial evaluated the use of aprepitant in combination with a 5-HT3 receptor antagonist and dexamethasone in patients with germ cell tumors who were receiving 5-day cisplatin combination chemotherapy. There was a significant reduction in the amount of emesis and use of rescue medications with the use of aprepitant. This study suggests that aprepitant may be useful in the prevention of CINV in multiday chemotherapy regimens.
Fosaprepitant dimeglumine, a water-soluble, phosphorylated analog of aprepitant, is rapidly converted to aprepitant after IV administration. Fosaprepitant (115 mg) was approved by the FDA as an alternative to the 125-mg oral aprepitant dose on day 1 of a 3-day regimen. As demonstrated in a randomized, double-blind study of patients receiving cisplatin chemotherapy, single-dose IV fosaprepitant (150 mg) given with ondansetron and dexamethasone was noninferior to the standard 3-day dosing of oral aprepitant in preventing CINV.
Steroids are sometimes used as single agents against mildly to moderately emetogenic chemotherapy but are more often used in antiemetic drug combinations.[Level of evidence: II];[68,69][Level of evidence: I] Their antiemetic mechanism of action is not fully understood, but they may affect prostaglandin activity in the brain. Clinically, steroids quantitatively decrease or eliminate episodes of N&V and may improve patients' mood, thus producing a subjective sense of well-being or euphoria (although they also can cause depression and anxiety). In combination with high-dose metoclopramide, steroids may mitigate adverse effects such as the frequency of diarrheal episodes.
Steroids are often given IV before chemotherapy and may or may not be repeated. Dosages and administration schedules are selected empirically. Dexamethasone is often the treatment of choice in treating N&V in patients receiving radiation to the brain, as it also reduces cerebral edema. It is administered orally, IM, or IV in the dose range of 8 mg to 40 mg (pediatric dose: 0.25–0.5 mg/kg).[70,71,72,73,74] Methylprednisolone is also administered orally, IM, or IV at doses and schedules that vary from 40 mg to 500 mg every 6 to 12 hours for up to 20 doses.[69,75]
Dexamethasone is also used orally for delayed N&V. Long-term corticosteroid use, however, is inappropriate and may cause substantial morbidity, including the following:
- Proximal muscle weakness (especially involving the thighs and upper arms).
- Aseptic necrosis of the long bones.
- Cataract formation.
- Hyperglycemia and exacerbation of preexisting diabetes or escalation of subclinical diabetes to clinical pathology.
- Adrenal suppression with hypocortisolism.
- Weight gain.
- GI irritation.
- Mood changes.
A study that examined chemotherapy in a group of patients with ovarian cancer found that short-term use of glucocorticoids as antiemetics had no negative effects on outcomes (e.g., overall survival or efficacy of chemotherapy). As previously shown with metoclopramide, numerous studies have demonstrated that dexamethasone potentiates the antiemetic properties of 5-HT3 -blocking agents.[77,78,79,80,81] If given IV, dexamethasone should be given over 10 to 15 minutes, since rapid administration may cause sensations of generalized warmth, pharyngeal tingling or burning, or acute transient perineal and/or rectal pain.[73,82,83,84]