60 PART TWO | CHEMOTHERAPY-INDUCED NAUSEA AND VOMITING studies included in our review are at variance with results from a recently performed systematic review and meta-analysis by Popovic et al [28], that showed that palonosetron was superior to first-generation 5-HT3 receptor antagonists in preventing acute and delayed CINV. Data from AC and non-AC MEC subgroups were pooled, therefore, this meta-analysis does not specifically address the efficacy of palonosetron for delayed CINV prophylaxis following non-AC MEC. Obviously, the two included studies regarding palonosetron [19, 20] have some limitations. Both have a crossover design, which causes a considerable risk of bias, including the possibility of a ‘carry over’ of treatment effect from one chemotherapy cycle to the next. The investigators haveminimized this risk by pooling data fromcycle 1 and 2. Moreover, the total number of included patients on non-AC MEC regimens was only 138. Also, multiday dexamethasone for the prevention of delayed CINV was not allowed in both trials, which is not consistent with current guideline recommendations. This could have influenced the outcome measures used in these studies. Furthermore, CR in the delayed phase was not a primary but secondary endpoint in the largest study. It is doubtful whether this trial was powered sufficiently to detect a difference in both endpoints. Considering this, we conclude that at present there is still insufficient data to decide whether palonosetron is the preferred 5-HT3 receptor antagonist following non-AC MEC. Current guidelines recommend the use of multiday dexamethasone to prevent delayed CINV after non-AC MEC. Dexamethasone use is often accompanied by unpleasant side effects. Reduction of dexamethasone exposure, without a decrease in efficacy, could be beneficial for patients. One study we included in our review reported that the efficacy of a single-day regimen of palonosetron and dexamethasone is non-inferior to palonosetron and multiday dexamethasone in the acute, delayed, and overall phases following non-AC MEC [18]. This evidence may be of particular benefit to patients undergoing multiple cycles of therapy when palonosetron is prescribed, and where the long-term side effects of dexamethasone can be reduced. While the major guidelines do not recommend the use of an NK1 receptor antagonist for non-AC MEC, there is some evidence that adding aprepitant may improve control of vomiting. Results from the study by Rapoport et al [21] show that a significantly higher proportion of patients on aprepitant reported the primary outcome of no vomiting during all phases. This study, however, has some limitations. For example, non-AC-MEC subgroup analysis was not predefined. Furthermore, multiday ondansetron was used as an active control arm for delayed CINV prophylaxis, which is not justified anymore by clinical evidence [29]. Data from two other included studies assessing NK1 receptor antagonists [22, 23] are in contrast with the study by Rapoport et al. Both studies were well-designed, and assessed the additional effect of NK1 receptor antagonists to first-generation 5-HT3 receptor antagonists in homogeneous patient populations with clearly defined tumor types, treated with oxaliplatin or carboplatin-based chemotherapy. Adding NK1 receptor antagonists did not improve CR rates during the acute and delayed phase. Therefore, we conclude that so far no convincing evidence exists indicating benefits from adding NK1 receptor antagonists to standard prophylactic antiemetic treatment following non-ACMEC.
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