Table 2. Comparison of Aprepitant and Standard Regimens continued...
Benzodiazepines such as lorazepam, midazolam, and alprazolam have become recognized as valuable adjuncts in the prevention and treatment of anxiety and the symptoms of anticipatory nausea and vomiting (ANV) associated with chemotherapy, especially with the highly emetogenic regimens given to children.[103,104,105] Benzodiazepines have not demonstrated intrinsic antiemetic activity as single agents. Therefore, their place in antiemetic prophylaxis and treatment is adjunctive to other antiemetic agents. Benzodiazepines presumably act on higher CNS structures, the brainstem, and spinal cord, and they produce anxiolytic, sedative, and anterograde amnesic effects. In addition, they markedly decrease the severity of EPRs, especially akathisia, associated with dopaminergic receptor antagonist antiemetics.
Lorazepam may be administered orally, IM, IV, and sublingually. Dosages range from 0.5 to 3 mg (alternatively, 0.025–0.05 mg/kg, or 1.5 mg/m2, but ≤4 mg per dose) in adults and 0.03 to 0.05 mg/kg in children every 6 to 12 hours.[Level of evidence: I][103,108,109] Midazolam produces mild-to-marked sedation for 1 to 4.5 hours at doses equal to 0.04 mg/kg given IV over 3 to 5 minutes.[110,111] Alprazolam has been shown to be effective when given in combination with metoclopramide and methylprednisolone.
The adverse effects of lorazepam include the following:
- Perceptual disturbances.
- Disorders of micturition and/or defecation.
- Visual disturbances.
- Anterograde amnesia.
- Psychological dependence.
- Depressed mental acuity with intoxication.
Olanzapine is an antipsychotic in the thienobenzodiazepine drug class that blocks multiple neurotransmitters: dopamine at D1, D2, D3, and D4 brain receptors; serotonin at 5-HT2a, 5-HT2c, 5-HT3, and 5-HT6 receptors; catecholamines at alpha-1 adrenergic receptors; acetylcholine at muscarinic receptors; and histamine at H1 receptors. Common side effects include the following:[115,116,117]
Olanzapine has also been associated with increased risk of hyperlipidemia, hyperglycemia, new-onset diabetes and, in rare cases, diabetic ketoacidosis.[115,117,118] Olanzapine should be used with caution in elderly patients; it has been associated with increased risk of death and increased incidence of cerebrovascular adverse events in patients with dementia-related psychosis and carries a boxed warning to that effect. Olanzapine's activity at multiple receptors, particularly at the D2 and 5-HT3 receptors that appear to be involved in N&V, suggests that it may have significant antiemetic properties.
There have been case reports on the use of olanzapine as an antiemetic.[Level of evidence: II];[120,121,122,123] These case reports prompted a phase I study in which olanzapine was used for the prevention of delayed emesis in cancer patients receiving their first cycle of chemotherapy consisting of cyclophosphamide, doxorubicin, cisplatin, and/or irinotecan. The protocol was completed by 15 patients, and no grade 4 toxicities were seen. The maximum tolerated dose was 5 mg/day for 2 days prior to chemotherapy and 10 mg/day for 7 days postchemotherapy. On the basis of these data, olanzapine appeared to be a safe and effective agent for the prevention of delayed emesis in chemotherapy-naive cancer patients receiving cyclophosphamide, doxorubicin, cisplatin, and/or irinotecan.