61 3 CHEMOTHERAPY-INDUCED NAUSEA AND VOMITING | PART TWO Some phase II studies suggested that adding a NK1 receptor antagonist to palonosetron and dexamethasone causes high CR rates in patients undergoing HEC or non-AC MEC. [30,31]. CR rates of more 95% and 85% could be achieved during the acute and delayed phase, respectively, for patients treated with carboplatin-based chemotherapy. This led to the drug development of NEPA, an oral fixed-dose combination of netupitant, which is a highly selective NK1 receptor antagonist, and palonosetron. We included the study by Gralla et al [24], which concluded that this combination drug was safe, well tolerated, and highly effective, when compared to oral 3-day aprepitant and palonosetron, and when both treatment groups are combined with dexamethasone. Because this study was designed primarily to assess the safety of NEPA, we believe that future RCTs should be performed to investigate the efficacy of NEPA in clearly predefined AC and non-AC MEC subgroups. New anti-CINV regimens for non-AC MEC are evolving. Recently, it was noticed that olanzapine, an atypical antipsychotic, combined with a single dose of dexamethasone and palonosetron was highly effective at controlling acute and delayed CINV in patients receiving HEC [32]. Tan et al. found highly significant CR rates for delayed CINV prophylaxis following non-AC MEC with multiday olanzapine compared to multiday dexamethasone [25]. Consequently, olanzapine could combine reduction of dexamethasone exposure with improved efficacy. This study has some limitations, however, like its open-label design, which could have influenced outcome measures. Moreover, AC and non-AC regimens were taken together in the subgroup analysis. Future studies in clearly defined non-AC MEC subgroups should assess whether the use of olanzapine results in better CR rates for delayed CINV after non-AC MEC. The antiemetic potential of megestrol acetate was assessed in one trial in a small population, receiving chemotherapy with mixed emetogenicity [26]. The authors reported highly significant CR rates for non-AC MEC treated patients, when megestrol acetate was compared to placebo. All patients received granisetron and metoclopramide, but corticosteroids were not allowed. Subgroup analysis for MEC contained both AC and nonAC regimens, which could influenced the results. Megestrol acetate should be compared in future trials with standard antiemetics. There are some limitations of this review. Data of the included RCTs could not be synthesized because of the heterogeneity of antiemetic regimens, patient populations and variance of primary outcomes. AC and non-AC MEC were often combined in subgroup analyses, making it hard to draw firm conclusions for non-AC MEC regimens. Conclusions High level evidence for optimal prophylaxis of delayed CINV after non-AC MEC is lacking. Further research is essential to improve antiemetic treatment efficacy and outcome while treatment (dexamethasone)-related toxicities are minimized and acceptable.
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