59 3 CHEMOTHERAPY-INDUCED NAUSEA AND VOMITING | PART TWO Olanzapine In 229 patients with a broad range of tumors, the efficacy of olanzapine was compared to the 5-HT3 receptor antagonist azasetron in an open-label trial by Tan et al [25]. Patients receiving HEC, AC, or non-AC MEC, were randomized to olanzapine 10 mg days 1-5 plus azasetron 10 mg iv. and dexamethasone 10 mg iv. on day 1, or to the control group with azasetron 10 mg iv. on day 1 plus dexamethasone 10 mg iv. days 1-5. Both chemotherapynaïve and non-naïve patients were included. Fifty-six percent of all randomized patients received AC or non-AC MEC. In this mixed subgroup, 55% of the patients received nonAC MEC, mainly oxaliplatin-based chemotherapy. The primary endpoint in this study was CR (no nausea and vomiting, no use of rescue medication) during the acute, delayed and overall phases. In the overall population, CR rates in the acute phase were very high (>95%), and did not significantly differ between olanzapine and 5-day dexamethasone in both the HEC and combined AC and non-AC MEC subgroups. In the combined subgroup, CR rates in the delayed phase were 83% for the olanzapine group vs. 58% for the control group (p < 0.05); in the overall phase 83% and 56%, respectively (p < 0.05). Megestrol acetate One hundred patients with gastrointestinal or lung cancer, who were treated with HEC or non-AC MEC (mainly oxaliplatin and irinotecan-based chemotherapy) were randomized in a single-blind, crossover trial published in 2011, to receive either oral megestrol acetate 320 mg or placebo [26]. Corticosteroids were not allowed in this study. Information on previous treatment with chemotherapy was not provided. CR rates in the acute, delayed, and overall phases were primary endpoints. In the non-AC MEC subgroup (44% of all patients), CR rates were significantly higher in the megesterol acetate group: in the overall phase 50% vs. 27.3%, respectively (p = 0.002); in the acute phase 72.7% vs. 59.1%, respectively (p = 0.146) and in the delayed phase 52.3% vs. 25.0% (p = 0.000), respectively. Discussion This review focuses on recent RCTs assessing prophylactic antiemetic treatment for delayed CINV following non-AC MEC. Results from the included trials show a diversity of antiemetic agents assessed. Because of heterogeneity in chosen endpoints, included populations, chemotherapy regimens, and tumor types, comparison of data from these studies is limited. There are, however, several findings of interest. We identified two trials comparing the efficacy of palonosetron to first-generation 5-HT3 receptor antagonists. Both studies suggest that palonosetron is equally effective as first- generation 5HT3 receptor antagonists for the prevention of acute and delayed CINV after non-AC MEC. This conclusion is consistent with results from recently performed study by Roscoe et al [27]. They found that, in patients treated with chemotherapy with mixed emetogenicity, including non-AC MEC, palonosetron was not more effective than granisetron in rates of average delayed nausea, which was the primary endpoint in this study, when both were combined with single-day dexamethasone and the dopamine (D2) receptor antagonist prochlorperazine. Because no non-AC MEC subgroup analysis was performed, this study did not meet selection criteria for inclusion in our review. On the other hand, the conclusions of both
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