Other Antiemetics
Medications from other drug classes have also been used as antiemetics for CINV. These include dopamine antagonists (prochlorperazine, promethazine), benzodiazepines (lorazepam), butyrophenones (droperidol, haloperidol), benzamides (metoclopramide), and cannabinoids. Many of these agents were used widely until more effective antiemetic agents became available. These agents remain useful for breakthrough symptoms or for patients who are refractory to standard therapy. The appropriate dosages and indications for these agents are shown in Table 7-3. Many of these agents have more side effects than standard agents, especially sedation and extrapyramidal side effects, such as dystonia and akathesia. Lorazepam is commonly used as a rescue antiemetic. Its mechanism of action as an antiemetic is not completely understood, but it may involve disruption of the cortical impulses to the VC, as well as anxiolytic activity. Because each patient has an individualized response to medicines, additional options for rescue antiemetics are needed.
Olanzapine is an atypical antipsychotic agent that antagonizes several serotonin and dopamine receptors as well as other neurotransmitter receptors. Its antiemetic action was first described in patients with refractory nausea or vomiting and advanced cancer.51,52,53 Preliminary studies have shown that olanzapine prevents acute and delayed CINV associated with moderately and highly emetogenic chemotherapy.54,55,56,57 In these trials, the complete response rate to antiemetic regimens containing olanzapine with dexamethasone plus either granisetron or palonosetron was 100% in the acute phase and 75% to 80% in the delayed phase. The usual dose of olanzapine ranges from 2.5 to 10 mg daily for control of refractory symptoms. The dose used in the CINV studies was 5 to 10 mg daily starting up to 2 days before the chemotherapy cycle. The common side effects of olanzapine include sleepiness, dry mouth, and dizziness, although these were not significant in the preliminary reports. Olanzapine is a good choice for control of refractory CINV symptoms, but further study is warranted before it should be routinely recommended for prophylaxis of CINV.
Cannabinoids have long been used for refractory nausea and vomiting. This is based on the effect of the CNS cannabinoid receptors on the CTZ, the NTS, and the VC.58 Small trials have shown conflicting effectiveness in the prevention of CINV.59,60 A new oral cannabinoid, nabilone, has recently been approved for the treatment of CINV in patients who do not respond adequately to other antiemetics.58 Cannabinoids are associated with side effects, such as drowsiness, dry mouth, dysphoria, vertigo, and euphoria. Although some patients have a clear preference for, and good response to, cannabinoids, side effects and a lack of pronounced efficacy limit their use in the general population of chemotherapy patients. These agents are usually reserved for patients who do not have adequate relief from other rescue medications, such as phenothiazines, benzodiazepines, or olanzapine.
Another agent being investigated for the control of CINV is gabapentin in doses of 300 to 900 mg daily for 5 days or more, combined with standard antiemetic regimens.61,62 In preliminary studies, gabapentin improved control of CINV symptoms and was well tolerated. Further studies are needed to define the role of gabapentin in CINV.
5. M.C. is at high risk for acute nausea and vomiting and for delayed symptoms as well. What would be the most appropriate antiemetic regimen for M.C.?
The optimal prophylactic antiemetic regimens depend on the emetic risk of the chemotherapy regimen. Treatment guidelines have been developed by several groups, including the American Society of Clinical Oncology (ASCO), the National Comprehensive Cancer Network (NCCN), and the Multinational Association of Supportive Care in Cancer (MASCC). These evidence- and consensus-based guidelines, which are largely in agreement with their recommendations, are summarized in Table 7-4.
For multiday chemotherapy regimens, prophylaxis with a serotonin antagonist and dexamethasone should be offered for each day that moderately or highly emetogenic chemotherapy is administered.11,14,16 Aprepitant might be useful in these situations, although it has not been studied in this context. Preliminary studies indicated that aprepitant was safe to administer for a total of 5 days. If multiday chemotherapy regimens have a high risk of delayed symptoms, then therapy for the delayed symptoms should be continued for at least 2 to 3 days after the last chemotherapy administration.
For M.C., the best regimen would include a single dose of a serotonin antagonist plus dexamethasone 12 mg oral or IV plus oral aprepitant 125 mg on day 1, then oral dexamethasone 8 mg on days 2 through 4 and oral aprepitant 80 mg on days 2 and 3. She should be offered medications for breakthrough CINV symptoms, such as prochlorperazine and lorazepam. She should be warned of the potential adverse effects of dexamethasone, especially hyperglycemia, and counseled to check her blood sugars more frequently and contact her physician if they remain elevated. M.C. should be advised to maintain a record of her symptoms and contact her physician if the breakthrough medications are not working or if she cannot keep fluids down.
Modern antiemetic regimens can achieve complete emetic control in about 70% to 90% of patients, but the response rate is lower for delayed CINV symptoms. If CINV symptoms are not adequately controlled, alterations in the antiemetic regimen should be made for the next cycle. Suggestions include
upgrading to the next higher emetogenicity level recommendation, adding aprepitant if not already given, and scheduling agents from other pharmacologic classes.
P.7p9
Table 7-4 Recommended Antiemetic Regimens by Emetogenicity of Chemotherapy Regimen | ||||||||||||||||||||||||||||
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Many patients may benefit from nondrug therapy for CINV symptoms, especially for anticipatory nausea and vomiting and anxiety. Techniques include guided imagery, hypnosis, relaxation techniques, systematic desensitization, and music therapy.63 Acupuncture and acupressure techniques have been investigated for use in CINV and some patients benefit from their use. The use of acupressure devices that stimulate the P6 point on the wrist have been proposed; however, in a controlled trial in patients with breast cancer, it was not found to be helpful.64 If patients are troubled by CINV symptoms, it is recommended that they refrain from heavy meals for 8 to 12 hours before the chemotherapy. They should also avoid heavy, greasy foods and food with strong aromas. Chewing gum can mask the metallic taste, which some patients perceive. Dry, salty foods can also help settle the stomach.
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