Chemotherapy induced nausea and vomiting (CINV) is a major adverse effect of chemotherapy and contributes to a decreased quality of life.1 In order to prevent CINV, prophylaxis with 5-hydroxytryptamine-3 (5-HT3) antagonists, neurokinin-1 (NK-1) antagonists and steroids (dexamethasone) are recommended in the National Comprehensive Cancer Network (NCCN) guidelines.2 However, breakthrough CINV may occur despite prophylaxis, which is often difficult to treat. The NCCN guidelines recommend treating breakthrough CINV with an agent that was not utilized in the prophylaxis regimen such as haloperidol, metoclopramide, promethazine or lorazepam.2 Recently, olanzapine has been investigated in the treatment of breakthrough CINV. Olanzapine acts on dopamine, 5-HT2c and 5-HT3 receptors that appear to be involved in nausea and vomiting.3 Olanzapine has been shown effective at relieving opioid-induced nausea in cancer patients in the past.4 The guidelines have now been updated to include olanzapine as an alternative due to a recent study comparing it to metoclopramide in breakthrough CINV.5
This trial was a randomized, double-blind, placebo-controlled trial including patients (>18yrs) that were chemotherapy naïve scheduled to receive highly emetogenic chemotherapy (HEC) with cisplatin (≥ 70mg/m2) or doxorubicin (≥ 50mg/m2) and cyclophosphamide (≥ 600mg/m2). All patients received prophylactic therapy with dexamethasone (12mg IV), palonosetron (0.25mg IV) and fosaprepitant (150mg IV) prior to chemotherapy with dexamethasone 4mg orally twice daily from days 2-4. The treatment arms were olanzapine 10mg orally daily with two placebos or metoclopramide 10mg orally every 8 hours for 72 hours. Only patients that experienced breakthrough nausea and/or vomiting received treatment; patients were to begin therapy within 30 minutes after experiencing vomiting or nausea and to stop the oral dexamethasone. The primary endpoint was the number of patients with no emetic episodes while the secondary endpoint was the number of patients with no nausea. Both emetic episodes and degree of nausea (on a visual analog scale) were reported by the patient every 24 hours. Safety evaluation was performed with the M.D. Anderson Symptom Inventory (MDASI) to identify side effects of treatment.
Demographics of the included patients were similar between groups. Of the randomized patients, 39% experienced breakthrough CINV with the majority occurring 2-3 days following chemotherapy and were included in the analysis. The study analyzed 56 patients in the olanzapine and 52 in the metoclopramide arm. Vomiting was relieved in 70% of the patients that received olanzapine and 31% of patients that received metoclopramide (p<0.01). Similarly, nausea was relieved by 68% and 23% in the olanzapine and metoclopramide groups, respectively (p<0.01). There were no significant side effects reported in either group. The authors concluded that olanzapine was more effective at relieving breakthrough CINV than metoclopramide.
The study showed promising results for the use of olanzapine for breakthrough CINV. A limitation of the study was that the dose of metoclopramide used was not maximized given the dose recommended in the guidelines is 10-40mg every 4 or 6hrs. The data was also patient reported which allows for variable results. Olanzapine does provide an advantage over oral metoclopramide in that it is dosed once daily rather than multiple times throughout the day. For patients experiencing nausea and/or vomiting, multiple oral doses may ...